Mini-fixed Twin Block Appliance: An Alternative to Fixed Functional Appliance in Noncompliant Class II Patients.

Class II malocclusion is the most common issue encountered in orthodontic practice. Myofunctional appliances are the most effective treatment option for skeletal class II malocclusion in growing age. Twin block is the most commonly used removable functional appliance, although its success is dependent upon patient compliance. The aim of this article is to present an effective modification of the conventional twin block appliance that can be used as an alternative to the fixed functional appliance in noncompliant skeletal class II patients with mandibular retrusion. How to cite this article: Khera AK, Raghav P, Wadhwa P. Mini-fixed Twin Block Appliance: An Alternative to Fixed Functional Appliance in Noncompliant Class II Patients. Int J Clin Pediatr Dent 2024;17(7):815-821.

The futuristic applications of transition metal dichalcogenides for cancer therapy.

The second-most common cause of death resulting from genetic mutations in DNA sequences is cancer. The difficulty in the field of anticancer research is the application of the traditional methods, which also affects normal cells. Mutations, genetic replication alterations, and chromosomal abnormalities have a direct impact on the effectiveness of anticancer drugs at different stages. Presently, therapeutic techniques utilize nanotechnology, transition metal dichalcogenides (TMDCs), and robotics. TMDCs are being increasingly employed in tumor therapy and biosensing applications due to their biocompatibility, adjustable bandgap, versatile functionality, exceptional photoelectric properties, and wide range of applications. This study reports the advancement of nanoplatforms based on TMDCs that are specifically engineered for responsive and intelligent cancer therapy. This article offers a thorough examination of the current challenges, future possibilities for theranostic applications using TMDCs, and recent progress in employing TMDCs for cancer therapy. Currently, there is significant interest in two-dimensional (2D) TMDCs nanomaterials as ultrathin unique physicochemical properties. These materials have attracted attention in various fields, including biomedicine. Due to their inherent ability to absorb near-infrared light and their exceptionally large surface area, significant efforts are being made to prepare multifunctional nanoplatforms based on 2D TMDCs.

Comparative evaluation of effectiveness of three versus four mini-implants for simultaneous intrusion and retraction of maxillary anterior teeth: A 3D FEM study.

OBJECTIVE: To evaluate and compare the displacement pattern of maxillary anterior teeth in the sagittal and vertical planes and evaluate the stress distribution in pdl, bone, teeth of the maxillary anterior region, and around the mini-implants during simultaneous en-masse retraction and intrusion using two, three, and four mini-implants combinations. METHODS: A three-dimensional FEM model of maxillary teeth and periodontal ligament housed in the alveolar bone with extracted first premolarswasgenerated. The models were broadly divided into three groups according to the number of mini-implants. Mini-implants were placed bilaterally between the second premolar and molar in group I, and along with bilateral implants, an additional mid-implant was placed between the central incisors as in group II, whereas in group III, anterior mini-implants were placed in between lateral incisors and canine bilaterally. RESULTS: The two mini-implant model showed the maximum amount of retraction in the sagittal plane followed by three and four mini-implant models. In the vertical plane, all six anterior teeth showed intrusion only in the four mini-implant model. The stress in cortical bone, cancellous bone, PDL, around the mini-implants, and in lateral incisor was maximum in the three mini-implant model, followed by four mini-implants with the least stress in the two mini-implant model. CONCLUSION: The four mini-implant model is better than the three and two mini-implants model as there is a more even distribution of force in the four mini-implants model as compared to the three mini-implants model.

Mechanism and potentialities of photothermal and photodynamic therapy of transition metal dichalcogenides (TMDCs) against cancer.

The ultimate goal of nanoparticle-based phototherapy is to suppress tumor growth. Photothermal therapy (PTT) and photothermal photodynamic therapy (PDT) are two types of physicochemical therapy that use light radiation with multiple wavelength ranges in the near-infrared to treat cancer. When a laser is pointed at tissue, photons are taken in the intercellular and intracellular regions, converting photon energy to heat. It has attracted much interest and research in recent years. The advent of transition materials dichalcogenides (TMDCs) is a revolutionary step in PDT/PTT-based cancer therapy. The TMDCs is a multilayer 2D nano-composite. TMDCs contain three atomic layers in which two chalcogens squash in the transition metal. The chalcogen atoms are highly reactive, and the surface characteristics of TMDCs help them to target deep cancer cells. They absorb Near Infrared (NIR), which kills deep cancer cells. In this review, we have discussed the history and mechanism of PDT/PTT and the use of TMDCs and nanoparticle-based systems, which have been practiced for theranostics purposes. We have also discussed PDT/PTT combined with immunotherapy, in which the cancer cell apoptosis is done by activating the immune cells, such as CD8+.

Anastomosing haemangioma of adrenal gland: an unusual vascular tumour.

With only 15 reported cases, anastomosing haemangioma of adrenal is a rare entity and usually presents as adrenal incidentaloma. A hypertensive, diabetic, non-smoker man in his late 60s presented with irritative voiding symptoms. On evaluation, he was found to have a urinary bladder mass and left adrenal incidentaloma measuring 8 cm. Metabolic evaluation confirmed it to be non-functional.The patient underwent transurethral resection of bladder tumour with left laparoscopic adrenalectomy. Intraoperatively, the adrenal tumour was highly vascular with multiple feeder vessels. Grossly it was soft, encapsulated with focal grey-brown areas. Microscopically, most of adrenal gland was replaced by anastomosing proliferating capillary vessels within framework of non-endothelial supporting cells reminiscent of splenic sinusoids. The tumour was positive for CD-31, CD-34, Glut-1 and SMA.Anastomosing haemangioma is a benign entity but it must be differentiated from angiosarcoma. Characteristic imaging features are not yet defined and is, therefore, difficult to diagnose preoperatively.

A Brief Review on Recent Developments in Diels-Alder Reactions.

The [4+2] Diels-Alder cycloaddition has been widely used for the synthesis of six-mem-ber scaffolds. In recent years, there have been significant developments in this area, including the discovery and design of novel dienes and dienophiles with improved reactivity and selectivity. These new building blocks can be used to develop diverse molecular structures with functional group compatibility. Additionally, there is the use of catalytic systems and metal-mediated reactions to enable asymmetric [4+2] cycloadditions, resulting in enantiomerically enriched products. Over-all, recent studies related to [4+2] Diels-Alder cycloaddition using numerous dienes, dienophiles, and catalysts in different reaction conditions have significantly improved the efficiency, selectivity, and versatility of the reaction, making it an increasingly important tool in the synthesis of complex organic molecules as presented in this review. These advancements offer exciting possibilities for the development of new methods and reagents for the construction of six-membered rings and the synthesis of bioactive compounds.

Synthesis, molecular docking and biological evaluation of 1,2,4-oxadiazole based novel non-steroidal derivatives against prostate cancer.

Prostate cancer is one of the most prevalent cancers in men leading to second most death causing cancer in men. Despite the availability of multiple treatment still the prevalence is high for prostate cancer. Steroidal antagonists associated with poor bioavailability, side effects while non-steroidal antagonists show serious side effects like gynecomastia. Therefore, there is a need of potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effect and minimal side effects. In the same context, we have designed the series, SP1-SP25 based 3-phenyl-5-styryl-1,2,4-oxadiazole as the core structure. We successfully synthesized all 25 molecules in this series and characterized them using 1H, 13C NMR, and mass spectroscopy. Subsequently, we conducted MTT assays using PC-3 cells and observed that all the compounds exhibited a dose-dependent decrease in cell viability. Notably, compounds SP04, SP16, and SP19 demonstrated a significant decrease in cell viability and exhibited potent activity compared to the other synthesized molecules and standard drug bicalutamide. Among them, SP04 emerged as the one of the most potent compounds with an IC50 value of 238.13 nM and an 89.99 % inhibition of PC-3 cells, compared to synthesized molecules and standard drug bicalutamide. Furthermore, we conducted ROS assays and androgen receptor inhibition assays using the potent compound SP04 and bicalutamide. The results indicated that SP04 increased ROS production and decreased androgen receptor expression dose-dependent manner. Additionally, we conducted a docking study to analyse the interaction patterns within the active site of the androgen receptor. ADMET analysis revealed that all the compounds exhibited favorable physicochemical properties and manageable toxicity profiles.

Unraveling the role of glial cell line-derived neurotrophic factor in the treatment of Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.

Development and Validation of Reverse-Phase High-Performance Liquid Chromatography Method for Simultaneous Estimation of Doxorubicin and Clotrimazole.

A reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed to analyze the simultaneous estimation of doxorubicin and clotrimazole. The method was achieved by Nucleodur C18 column with dimension 250 × 4.6 mm (5 µm) using gradient elution. The mobile phase contained 0.2% formic acid (pH 3.2) and acetonitrile. The flow rate was kept at 1.0 mL/min and detection and quantitation of both drugs (doxorubicin and clotrimazole) were achieved using a photodiode array detector at 276 nm, which was the isosbestic point for both drugs. The proposed method was validated according to the current International Council for Harmonization of Technical Requirements of Pharmaceuticals for Human Use guidelines for specificity, linearity, accuracy, precision, and robustness. The developed method showed a linear response (R2 > 0.999), and was accurate (recoveries 97%-103%), precise (resolution ≤1.0%), sensitive, and specific. Thus, the developed RP-HPLC method for the simultaneous estimation of both drugs was successfully validated and can be utilized for the estimation of these drugs in the formulations being developed.

Natural Alternatives to Non-biodegradable Polymers in 3D Printing of Pharmaceuticals.

BACKGROUND: Due to potential toxicity, non-biodegradable polymers used in 3D (3-dimensional) printing of drugs could be dangerous for patient safety and the environment. OBJECTIVE: This review aims to investigate the toxicity of non-biodegradable polymers and investigate the use of natural materials as an alternative in 3D printing medicines. The study evaluates the dangers connected to 3D printing. METHODS: A review of the literature on various 3D printing processes, such as inkjet printing, fused filament manufacturing, and extrusion-related 3DP systems, was done for this study. Also, the use of cellulose derivatives and natural materials in 3D printing and their potential as active excipients was proposed. RESULTS: The review identified potential toxicity risks linked to non-biodegradable polymers used in drug 3D printing. As a potential fix for this issue, the use of natural materials with improved mechanical and thermal properties was explored. The use of cellulose derivatives as an alternative to non-biodegradable polymers in 3D printing pharmaceuticals was also investigated in the study. CONCLUSION: This study emphasises the significance of evaluating the risks connected to drug 3D printing and recommends using natural materials as an alternative to non-biodegradable polymers. More study is required to create secure and reliable 3D printing processes for pharmaceuticals.

Barriers to the effective management and prevention of post kala-azar dermal leishmaniasis (PKDL) in the Indian subcontinent.

Post kala-azar dermal leishmaniasis (PKDL) is a skin disease that usually occurs among individuals with a past history of visceral leishmaniasis (VL). PKDL cases act as a reservoir of parasites and may play a significant role in disease transmission. Hence, prompt detection and complete treatment of PKDL cases are crucial for the control and elimination of VL. The purpose of this review was to highlight the barriers to effective control and prevention of VL/PKDL as well as potential solutions in India. Main obstacles are lack of knowledge about the disease and its vector, poor treatment-seeking behaviours, ineffective vector control measures, lack of confirmatory diagnostics in endemic areas, limited drug choices, treatment noncompliance among patients, drug resistance, and a lack of an adequate number of trained personnel in the health system. Therefore, in order to control and successfully eliminate VL in the Indian subcontinent, early detection of PKDL cases, improved diagnosis and treatment, raising awareness, and effective vector control mechanisms are necessary.

Therapeutic charisma of imidazo [2,1-b] [1,3,4]-thiadiazole analogues: a patent review.

Imidazothiadiazole was discovered around the 1950s era, containing an imidazole ring fused to a thiadiazole ring. Imidazothiadiazole exhibit versatile pharmacological properties including anticonvulsant, cardiotonic, anti-inflammatory, diuretic, antifungal, antibacterial and anticancer. Despite of the being discovered in 1950s, the imidazothiadiazole derivatives are unable to being processed to clinical trials because of lack of bioavailability, efficacy and cytotoxicity. The recent patent literature focused on structural modification of imidazothiadiazole core to overcome these problems. This review limelight a disease-centric perspective on patented imidazothiadiazole from 2015-2023 and to understand their mechanism of action in related diseases. The relevant granted patent applications were located using patent databases, Google Patents, USPTO, EPO, WIPO, Espacenet and Lens.

A Rationalized Approach to Design and Discover Novel Non-steroidal Derivatives through Computational Aid for the Treatment of Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most prevalent cancers in men, leading to the second most common cause of death in men. Despite the availability of multiple treatments, the prevalence of prostate cancer remains high. Steroidal antagonists are associated with poor bioavailability and side effects, while non-steroidal antagonists show serious side effects, such as gynecomastia. Therefore, there is a need for a potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effects, and minimal side effects. OBJECTIVE: This current research work focused on identifying a novel non-steroidal androgen receptor antagonist through computational tools, such as docking and in silico ADMET analysis. METHODS: Molecules were designed based on a literature survey, followed by molecular docking of all designed compounds and ADMET analysis of the hit compounds. RESULTS: A library of 600 non-steroidal derivatives (cis and trans) was designed, and molecular docking was performed in the active site of the androgen receptor (PDBID: 1Z95) using AutoDock Vina 1.5.6. Docking studies resulted in 15 potent hits, which were then subjected to ADME analysis using SwissADME. ADME analysis predicted three compounds (SK-79, SK-109, and SK-169) with the best ADME profile and better bioavailability. Toxicity studies using Protox-II were performed on the three best compounds (SK-79, SK-109, and SK-169), which predicted ideal toxicity for these lead compounds. CONCLUSION: This research work will provide ample opportunities to explore medicinal and computational research areas. It will facilitate the development of novel androgen receptor antagonists in future experimental studies.

Optimisation of a Greener-Approach for the Synthesis of Cyclodextrin-Based Nanosponges for the Solubility Enhancement of Domperidone, a BCS Class II Drug.

BCS class II molecules suffer from low oral bioavailability because of their poor permeability and sub-optimal aqueous solubility. One of the approaches to enhance their bioavailability is using cyclodextrin-based nanosponges. This study aimed to optimise and evaluate the feasibility of a microwave-assisted approach to synthesise nanosponges and improve domperidone's solubility and drug delivery potential. In the production process, microwave power level, response speed, and stirring speed were optimised using the Box-Behnken approach. Ultimately, the batch with the smallest particle size and highest yield was chosen. The optimised method of synthesis of the nanosponges resulted in a product yield of 77.4% and a particle size of 195.68 ± 2.16 nm. The nanocarriers had a drug entrapment capacity of 84 ± 4.2% and a zeta potential of -9.17± 0.43 mV. The similarity and the difference factors demonstrated proof-of-concept, showing that the drug release from the loaded nanosponges is significantly greater than the plain drug. Additionally, spectral and thermal characterisations, such as FTIR, DSC, and XRD, confirmed the entrapment of the drug within the nanocarrier. SEM scans revealed the porous nature of the nanocarriers. Microwave-assisted synthesis could be used as a better and greener approach to synthesise these nanocarriers. It could then be utilised to load drugs and improve their solubility, as seen in the case of domperidone.

Recent advances of benzimidazole as anticancer agents.

Cancer is the second leading cause of death globally, with 9.6 million deaths yearly. As a life-threatening disease, it necessitates the emergence of new therapies. Resistance to current chemotherapies drives scientists to develop new medications that will eventually be accessible. Because heterocycles are so common in biological substances, compounds play a big part in the variety of medications that have been developed. The "Master Key" is the benzimidazole nucleus, which consists of a six-membered benzene ring fused with a five-membered imidazole/imidazoline ring, which is an azapyrrole. One of the five-membered aromatic nitrogen heterocycles identified in American therapies that have been approved by the Food and Drug Administration (FDA). Our results show that benzimidazole's broad therapeutic spectrum is due to its structural isosteres with purine, which improves hydrogen bonding, electrostatic interactions with topoisomerase complexes, intercalation with DNA, and other functions. It also enhances protein and nucleic acid inhibition, tubulin microtubule degeneration, apoptosis, DNA fragmentation, and other functions. Additionally, readers for designing the more recent benzimidazole analogues as prospective cancer treatments.

A Review on Modern Approaches to Benzimidazole Synthesis.

Cancer is the second most source of cessation of life globally, with 9.6 million expirations at each stage around the globe. The resistance to the current chemotherapies urges researchers to develop new drugs to be available in the market. Among the wide range of drugs synthesized, heterocyclic compounds play a major role due to the abundance of heterocyclic rings in biological substances. In medicinal chemistry, benzimidazole is an important pharmacophore and a privileged structure. This bicyclic compound is made up of the fusion of a six-membered benzene ring and a five-membered imidazole ring with two nitrogen atoms at 1,3-positions. The benzimidazole ring has a great deal of stability. Many strong acids and alkalis do not affect benzimidazoles. The benzene ring of benzimidazole cleaves only under extreme conditions. Except in certain circumstances, the benzimidazole ring is also quite resistant to reduction. It is the most popular nucleus to study because of its wide range of biological functions. The recently developed methods for preparing benzimidazoles, such as condensation of o-phenylene diamines (OPDs) with aldehydes and many others using a wide range of nano, metal-based catalysts under solventfree conditions, are discussed in detail in the current studies.

Marine-derived Natural Products as Anticancer Agents.

Cancer is a deadly human disease on the rise due to changes in lifestyle, nutrition, and global warming. Cancer is characterized by uncontrolled, disordered, and undesired cell division. About 60% of cancer medicines approved by the FDA are made from natural ingredients. Intensive efforts over the last decade to better understand the vast chemical diversity provided by marine life have resulted in an intriguing "marine pipeline" of potential anticancer clinical and preclinical treatments. The molecular targets of marine products as anticancer drugs, as well as different reported compounds acting on distinct targets, are the topic of this review.

Role of Tyrosine Kinases and their Inhibitors in Cancer Therapy: A Comprehensive Review.

BACKGROUND: Cancer has been recognized as one of the non-communicable diseases with an increasing number of new cases, higher morbidity, and higher mortality rates at the global level. Thus, there is non-stop search for novel targets and small molecules to improve the chemotherapeutic outcomes concerning potency, selectivity, efficiency, affinity, ADMET, etc. Among anticancer therapeutic targets, tyrosine kinase has been documented well and approved as an important target with the development of various clinically used drugs. There are several structurally diverse small molecules in different preclinical and clinical stages of development that act by affecting tyrosine kinases in cancerous cells. Here, we have summarized different potent molecules acting against tyrosine kinases that can be considered as anticancer agents. OBJECTIVE: The current review focused on structural aspects of different chemical agents for inhibition of tyrosine kinases as anticancer agents. METHODS: The present study provides a summarized review of published information on tyrosine kinase inhibitors, their binding pattern, potencies, and structure-activity relationships. The review also highlighted the structural aspects of the interaction between inhibitors and amino acid residues of tyrosine kinases. Moreover, it also provided a summary of different types of cancers and the currently available options for treatment. RESULTS: Several studies are being conducted for the inhibition of different tyrosine kinases using small molecules for the treatment of cancer. Tyrosine kinases have been reported involving in routine cellular functions, growth, and division of cells through different pathways which depend on phosphorylation. The overexpression and uncontrolled activity of tyrosine kinases have been identified as an important feature of cancerous cells. Thus, various small molecules have been reported which inhibit tyrosine kinases to block the growth and division of cancer cells. Here, more than 30 highly potent inhibitors of tyrosine kinases are summarised, which consist of pyrimidine, pyrazole, triazine, quinazoline, quinoline, pyrazine, chromene, etc. rings as a basic skeleton with different substituents. CONCLUSION: Inhibition of tyrosine kinases by different small molecules is an approved strategy for the development of novel anticancer agents. Several published reports have mentioned the characteristics of the different binding sites and crucial residues in tyrosine kinases for the design of novel molecular inhibitors. However, selectivity is an important criterion for the development of chemotherapeutic agents due to the existence of approximately 30 families of tyrosine kinases.

Recent Developments in the Synthesis and Anticancer Activity of Indole and Its Derivatives.

Heterocyclic compounds are a class of compounds that is deeply intertwined with biological processes and is found in about 90% of commercially available medicines. They serve a critical function in medicinal chemistry and are focused in the field of medication development for their intensive research due to their broad variety of biological effects because of their intriguing molecular architecture, such as indoles are good candidates for drug development. It is a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring with several pharmacophores that yield a library of different lead compounds. Human cancer cells have been demonstrated to be inhibited by indoles in the development of new anticancer medicines. This is the first comprehensive review to focus on current methodologies for incorporating indole moiety, with their mechanistic targets as anticancer drugs, in order to shed light on the logical development of indole-based anticancer treatment options with high efficacy. This compiled data may serve as a benchmark for modifying existing ligands in order to design novel potent molecules through excellent yield synthesis techniques.

Wave-assisted techniques, a greener and quicker alternative to synthesis of cyclodextrin-based nanosponges: A review.

The ever-increasing applications of cyclodextrin and cyclodextrin-based nanosponges in formulation development has gained much attention from researchers towards needed research in this arena. Nanosponges are three-dimensional nanoporous versatile carriers, in the pharmaceutical research field on account of their capability, to encapsulate lipophilic and hydrophilic drugs both in their crystalline structure by inclusion and non-inclusion phenomenon. This review sheds light on the advancements made in this field with regard to their synthesis while zooming in on the utilization of two novel energies (Microwave and ultrasonic) in accomplishing this goal and its future thereof. Microwave and ultrasound-assisted manufacturing of cyclodextrin-based nanosponges (CD-NS) has been found superior to conventional heat-dependent methods due to rapid/homogenous heating and fast kinetics, which ultimately provide the final product with high yield and crystallinity relatively rapidly. The review article also defines several facets of microwave and ultrasound-assisted nanosponge synthesis including the synergism of microwave and ultrasonic energy and the theories behind them. This hitherto unexplored microwave-ultrasonic coupling technology could be a future technology to synthesize CD-NS with a better outcome. In the recent past, these novel energy processes have been used successfully in material synthesis at an industrial scale, due to their swift and streamlined synthesis attributes. Likewise, these wave-assisted methods have the full potential to materialize the concept of CD-NS from lab scale to industrial scale as a competent and versatile drug carrier, having all the prerequisite characteristics, for commercialization.