Impact of Orthodontic Treatment on the Incidence of Dental Caries in Adolescents: A Prospective Cohort Study.

BACKGROUND: Orthodontic treatment is a widely embraced intervention aimed at enhancing dental aesthetics and correcting malocclusions among adolescents. However, concerns persist regarding its potential impact on oral health, particularly on the development of dental caries. This study aimed to systematically investigate the relationship between orthodontic treatment and the incidence of new carious lesions among adolescents. METHODS: A prospective cohort design involving adolescents aged 12-18 years was employed. A total of 82 patients met the inclusion criteria. In addition, an age-matched control group of 82 participants who did not undergo orthodontic treatment was included. The study included both a treatment group undergoing orthodontic treatment (braces or aligners) and an age-matched control group that did not undergo any orthodontic intervention. Demographic characteristics, orthodontic treatment details, and oral hygiene practices were documented at baseline and throughout the study period. Dental examinations at six-month intervals post-treatment were conducted to track the incidence and progression of carious lesions. RESULTS: The demographic characteristics, baseline oral health status, orthodontic treatment details, and oral hygiene practices were comparable between the treatment and control groups. Post-orthodontic treatment assessment revealed a slightly higher incidence of new carious lesions in the treatment group (14.6%) than in the control group (9.8%), although this difference was not statistically significant (p = 0.15). Dental examinations at six-month intervals demonstrated a gradual increase in caries incidence over time in both groups, with no substantial disparities observed. CONCLUSIONS: This study provides a comprehensive examination of the relationship between orthodontic treatment and the incidence of new carious lesions among adolescents. While a trend towards higher caries incidence in the treatment group was observed, the difference was not statistically significant. These findings contribute to the existing body of knowledge and emphasize the need for ongoing research to guide clinical practice.

Design, synthesis and in vitro cytotoxicity evaluation of indolo-pyrazoles grafted with thiazolidinone as tubulin polymerization inhibitors.

In the pursuit of potential and effective chemotherapeutic agents, a series of 2-((3-(indol-3-yl)-pyrazol-5-yl)imino)thiazolidin-4-ones was designed and synthesized, conjoining salient pharmacophoric properties for directing prominent cytotoxicity. The in vitro cytotoxicity evaluation revealed potent compounds with IC50 values <10 µM on tested human cancer cell lines. Compound 6c exhibited the highest cytotoxicity with an IC50 value of 3.46 µM against melanoma cancer cells (SK-MEL-28) and was highly cytospecific and selective towards cancer cells. The traditional apoptosis assays revealed morphological and nuclear alterations such as apoptotic body formation, condensed/horseshoe-shaped/fragmented/blebbing nuclei, and the generation of ROS. Flow cytometric analysis revealed effective early-stage apoptosis induction and cell-cycle arrest in the G2/M phase. In addition, the enzyme-based effect of 6c on tubulin showed the inhibition of tubulin polymerization (about 60% inhibition, IC50 was <1.73 µM). Moreover, molecular modeling studies affirmed the constant accommodation of compound 6c at the active pocket of tubulin, establishing many electrostatic and hydrophobic interactions with the active pocket's residues. The tubulin-6c complex was stable during the MD simulation for 50 ns with the recommended range of RMSD value (2-4 Å) for each pose.

Synthesis and cytotoxicity evaluation of DNA-interactive ß-carboline indolyl-3-glyoxamide derivatives: Topo-II inhibition and in silico modelling studies.

In a quest for effective cancer targeted drug therapy, a series of new ß-carboline tethered indole-3-glyoxylamide derivatives, conjoining salient pharmacophoric properties with prominent cytotoxicity, were synthesized. The in vitro cytotoxic ability of the compounds was established, and many of the compounds exhibited remarkable cytotoxicity (IC50 < 10 µM) on human cancer cell lines like HCT116, A549, SK-MEL-28, and MCF7. Precisely, compound 12x expressed the best cytotoxic potential against melanoma cancer cell line (SK-MEL-28) with an IC50 value of 4.37 µM. In addition, cytotoxicity evaluation against normal kidney cell line (NRK52E) entrenched the cytospecificity and selectivity index of 12x. The traditional apoptosis assays advised morphological and nuclear alterations such as apoptotic body formation, condensed/horseshoe-shaped/fragmented nuclei, and generation of ROS. The flow cytometric analysis revealed significant early and slight late-stage induction of apoptosis. The target-based physiochemical assays indicated the ability of compound 12x to bind with DNA and inhibition of Topoisomerase II. Moreover, molecular modeling studies affirm the excellent DNA intercalation potential and stabilized interactions of 12x with DNA base pairs. In silico prediction of physicochemical parameters revealed the promising drug-like properties of the synthesized derivatives.

Current advances in the synthetic strategies of 2-arylbenzothiazole.

Benzothiazole is a privileged scaffold in the field of synthetic and medicinal chemistry. Its derivatives and metal complexes possess a gamut of pharmacological properties and high degree of structural diversity that has proven it vital for the investigation for novel therapeutics. The 2nd position of benzothiazole is the most active site that makes 2-arylbenzothiazole as felicitous scaffolds in pharmaceutical chemistry. The extensive significance of benzo-fused heterocyclic moieties formation has led to broad and valuable different approaches for their synthesis. This review deals with the synthetic approaches developed so far for the synthesis of 2-arylbenzothiazoles. Moreover, this article abridges the publications devoted to the synthesis of this moiety over the last 6 years. This study gives a current precis of research on the fabrication of 2-arylbenzothiazoles through different synthetic pathways and shall be helpful for researchers and scientists who are working in this field to make more potent biologically active benzothiazole-based drugs.

Dithiocarbamation of spiro-aziridine oxindoles: a facile access to C3-functionalised 3-thiooxindoles as apoptosis inducing agents.

Herein, we report the first dithiocarbamation of spiro-aziridine oxindoles involving regiospecific ring-opening by using in situ generated nucleophilic dithiocarbamates as an instant source of sulfur. This approach afforded C3-functionalised-3-thiooxindoles in good to excellent yields with a wide substrate scope under catalyst-free and mild reaction conditions. These compounds were screened for their anticancer activity against a panel of human cancer cell lines, wherein compound 3u exhibited significant cytotoxic activity against human lung cancer cells with an IC50 value of 4.31 ± 1.88 µM. Phase contrast microscopy as well as different staining assays such as acridine orange/ethidium bromide (AO/EB), DAPI and DCFDA demonstrated the induction of apoptosis in A549 lung cancer cells after treatment with compound 3u. In addition, the clonogenic assay and migration assay demonstrated the ability of compound 3u to inhibit colony formation and cell migration, respectively, in A549 cells in a dose-dependent manner.

ß-Carboline tethered cinnamoyl 2-aminobenzamides as class I selective HDAC inhibitors: Design, synthesis, biological activities and modelling studies.

The effect of ß-carboline motif as cap for HDAC inhibitors containing cinnamic acid as linker and benzamides as zinc binding group was examined in this study. A series of ß-carboline-cinnamide conjugates have been synthesized and evaluated for their HDAC inhibitory activity and in vitro cytotoxicity against different human cancer cell lines. Almost all the compounds exhibited superior HDAC inhibitory activity than the standard drug Entinostat for in vitro enzymatic assay. Among the tested compounds, 7h displayed a noteworthy potency with an IC50 value of 0.70 ± 0.15 µM against HCT-15 cell line when compared to the standard drug Entinostat (IC50 of 3.87 ± 0.62 µM). The traditional apoptosis assays such as nuclear morphological alterations, AO/EB, DAPI, and Annexin-V/PI staining revealed the antiproliferative activity of 7h while depolarization of mitochondrial membrane potential by JC-1 was observed in dose-dependent manner. Cell cycle analysis also unveiled the typical accumulation of cells in G2M phase and sub-G1/S phase arrest. In addition, immunoblot analysis for compound 7h on HCT-15 indicated selective inhibition of the protein expression of class I HDAC 2 and 3 isoforms. Molecular docking analysis of compound 7h revealed that it can prominent binding with the active pocket of the HDAC 2. These finding suggest that the compound 7h can be a promising lead candidate for further investigation in the development of novel anti-cancer drug potentially inhibiting HDACs.

ß-Carboline-based molecular hybrids as anticancer agents: a brief sketch.

Cancer is a huge burden on the healthcare system and is foremost cause of mortality across the globe. Among various therapeutic strategies, chemotherapy plays an enormous role in overcoming the challenges of treating cancer, especially in late stage detection. However, limitations such as extreme side/adverse effects and drug resistance associated with available drugs have impelled the development of novel chemotherapeutic agents. In this regard, we have reviewed the development of ß-carboline-based chemotherapeutic agents reported in last five years. The review mainly emphasizes on the molecular hybrids of ß-carbolines with various pharmacophores, their synthetic strategies, and in vitro anticancer evaluation. In addition, the mechanisms of action, in silico studies, structural influence on the potency and selectivity among diverse cancer cell lines have been critically presented. The review updates readers on the diverse molecular hybrids prepared and the governing structural features of high potential molecules that can help in the future development of novel cytotoxic agents.

Exploration of Potent Multi-target-directed-ligands as Anti-alzheimer's Disease Agents: A Moiety Based Review.

Dementia is a chronic neurodegenerative disease, and a maximum number of the cases are directly related to Alzheimer's disease. More than 4 million people are living with Alzheimer's disease-related dementia in India, making it a national crisis. Alzheimer's disease deteriorates cognitive functions with the passage of time and consists of multi-faceted factors, such as the decline of acetylcholine level, amyloid ß-aggregation, tau hyperphosphorylation, oxidative stress, etc. The classical drugs used to date, are focused on only one target and are not serving the cause properly. Hence, the community of scientists is rigorously working on multi-target-directed agents that incorporate two or more active scaffolds in one compound or hybrid of active moieties. This article aims to evaluate novel potential compounds and moieties, such as quinolines, chalcones, coumarins, chromenes, piperazine, carbazoles, cinnamic acids, tacrine hybrids, donepezil hybrids, etc., that have been introduced as multi-target-directed agents in the recent five years.

New Insights into the Microstructural Analysis of Graphene Oxide.

AIM AND OBJECTIVE: To explore the impact of synthesis conditions (temperature and time) on the properties of developed Graphene Oxide (GO). BACKGROUND: A highly promising approach has been used for the synthesis of graphene oxide (GO) from graphite flakes using the modified Hummers method. Concentrated sulfuric acid was used as an intercalating agent and the oxidation was done with the help of potassium permanganate and hydrogen peroxide. METHODS: The present method does not need expensive membranes for the filtration of Carbon and metalcontaining residues. The pre-cooling method is used to eradicate the explosive behavior of intermediate steps. The high quality of synthesized graphene oxides was confirmed by a series of characterization techniques, including Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, energy-dispersive X-ray spectroscopy, and atomic force microscopy. RESULTS: The results indicated the presence of Oxygen-containing functional groups, and a rise in the Oxygen content confirmed the synthesis of high-quality graphene oxide. CONCLUSION: As per obtained experimental findings and subsequent analysis, the synthesized high-quality graphene oxide could be used in the design of membranes for water treatment applications.

The microwave-assisted syntheses and applications of non-fused single-nitrogen-containing heterocycles.

Microwave technology has emerged as a great tool for the efficient synthesis of organic compounds and it provides opportunities for chemists to achieve chemical transformations that tend to be challenging using classical approaches. Additionally, N-heterocycles are well-known for their medicinal/biological significance, along with their applications as excellent building blocks in chemical synthesis. The dominance of N-heterocycles in drug molecules and other pharmacological agents makes them attractive scaffolds, which encourages chemists to develop a wide range of strategies towards the greener synthesis and functionalization of these heterocycles. In this regard, we have collated and discussed literature relating to the microwave-assisted synthesis and the modification of non-(benzo)fused single-nitrogen-containing N-heterocycles from the past decade. The role of the microwave technique and its benefits over the conventional approach have also been emphasized in terms of overall reaction efficiency, reaction time, yield, reduced side-product generation, neat and clean reactions, chemo-/regio-/enantio-selectivity, and the use of mild reagents/reaction conditions to achieve the objectives of green and sustainable chemistry.

Saturated Five-Membered Thiazolidines and Their Derivatives: From Synthesis to Biological Applications.

In past decades, interdisciplinary research has been of great interest for scholars. Thiazolidine motifs behave as a bridge between organic synthesis and medicinal chemistry and compel researchers to explore new drug candidates. Thiazolidine motifs are very intriguing heterocyclic five-membered moieties present in diverse natural and bioactive compounds having sulfur at the first position and nitrogen at the third position. The presence of sulfur enhances their pharmacological properties, and, therefore, they are used as vehicles in the synthesis of valuable organic combinations. They show varied biological properties viz. anticancer, anticonvulsant, antimicrobial, anti-inflammatory, neuroprotective, antioxidant activity and so on. This diversity in the biological response makes it a highly prized moiety. Based on literature studies, various synthetic approaches like multicomponent reaction, click reaction, nano-catalysis and green chemistry have been employed to improve their selectivity, purity, product yield and pharmacokinetic activity. In this review article, we have summarized systematic approaches for the synthesis of thiazolidine and its derivatives, along with their pharmacological activity, including advantages of green synthesis, atom economy, cleaner reaction profile and catalyst recovery which will help scientists to probe and stimulate the study of these scaffolds.

Contemporary Progress in the Synthetic Strategies of Imidazole and its Biological Activities.

Heterocyclic compounds are pervasive in many areas of life and one of the heterocycles, imidazole is a unique heterocyclic five-membered aromatic compound having two sp2 hybridized nitrogen atoms. Its integral name is 1, 3 diazole and previously, it was known as glyoxalin. This moiety has achieved a considerable place among scientists in recent years by reason of its divergent synthetic strategies and uncommon biological and pharmacological activities, for example, anti-convulsant, anti-microbial, anti-cancer, anti-inflammatory, anti-tumor, anti-viral, anti-ulcer, analgesic, etc. Due to distinct therapeutic actions, it is still an engrossed area of research. Researchers currently are inventing new greener methods to synthesize its derivatives and to improve its pharmacological activities. The purpose of this review is to study the literature that can help researchers to explore this area, its prevailing program for synthesis in environmentally friendly conditions and biological profile throughout past decades.

Evaluation of determinants for the nickel release by the standard orthodontic brackets.

AIM: The study was aimed to assess the effect of different pH and immersion time on the amount of nickel release from simulated orthodontic appliance of 3M Unitek company. MATERIAL AND METHOD: Nickel ion release was evaluated after subjecting the brackets to the simulated artificial oral environment. In this study, 90 stainless steel brackets of 3M Unitek Company were tested by immersing them in artificial saliva of pH 4.2, pH 6.5 and pH 7.6 for a time interval of 1hour, 1 week and 1 month (T1 - 1h, T2 - 7 days, T3 - 30 days) respectively. The data was subjected for the one-way ANOVA and the post-hoc test for the statistical comparison. RESULTS: Means of 2.99±0.77, 9.53±4.26 and 12.65±2 .52 ppb (parts per billion by volume) of nickel were released for 4.2 pH at a time interval of 1hour, 7 days and 1 month respectively. Means of 5.37±2.26, 10.94±1.51 and 16.92±1.69 ppb of nickel were released for 6.5 pH at a time interval of 1hour, 7 days and 1 month respectively. A mean of 2.13±0.92, 0.74±0.54 and 18.83±1.02 ppb of nickel was released for 7.6 pH at a time interval of 1 hr, 7 days and 1 month respectively. CONCLUSION: pH of the artificial saliva significantly affected the amount of nickel release. Acidic pH was found to increase the amount of nickel release in the artificial saliva. Time duration of bracket immersion significantly affected the amount of nickel release.

Evaluation of Pharyngeal Space in Different Combinations of Class II Skeletal Malocclusion.

OBJECTIVES: The study was aimed to evaluate the pharyngeal airway linear measurements of untreated skeletal class II subjects with normal facial vertical pattern in prognathic maxilla with orthognathic mandible and orthognathic maxilla with retrognathic mandible. MATERIALS AND METHOD: the sample comprised of lateral Cephalograms of two groups (30 each) of class II malocclusion variants. Group 1 comprised of class II malocclusion with prognathic maxilla and orthognathic mandible, whereas group 2 comprised of class II malocclusion with orthognathic maxilla and retrognathic mandible. Each group was traced for the linear measurements of the pharyngeal airway like the oropharynx, nasopharynx and soft palate. The obtained data was subjected to independent t test and the Mann Whitney test to check the difference between the two groups and within the groups respectively. RESULTS: there was significant difference between all the linear measurements at the soft palate region and the distance between the tip of soft palate to its counter point on the pharyngeal wall in oropharynx region (p-ppm). CONCLUSION: the pharyngeal airway for class II malocclusion with various combination in an average growth pattern adult showed significant difference. The present results suggested, that the pharyngeal airway space might be the etiological factor for different sagittal growth pattern of the jaws and probable usage of different growth modification appliance can influence the pharyngeal airway.