Strategies in synthetic design and structure-activity relationship studies of novel heterocyclic scaffolds as aldose reductase-2 inhibitors.

Heterocyclic scaffolds of natural as well as synthetic origin provide almost all categories of drugs exhibiting a wide range of pharmacological activities, such as antibiotics, antidiabetic and anticancer agents, and so on. Under normal homeostasis, aldose reductase 2 (ALR2) regulates vital metabolic functions; however, in pathological conditions like diabetes, ALR2 is unable to function and leads to secondary diabetic complications. ALR2 inhibitors are a novel target for the treatment of retinopathy (cataract) influenced by diabetes. Epalrestat (stat), an ALR2 inhibitor, is the only drug candidate that was approved in the last four decades; the other drugs from the stat class were retracted after clinical trial studies due to untoward iatrogenic effects. The present study summarizes the recent development (2014 and onwards) of this pharmacologically active ALR2 heterocyclic scaffold and illustrates the rationale behind the design, structure-activity relationships, and biological studies performed on these molecules. The aim of the current review is to pave a straight path for medicinal chemists and chemical biologists, and, in general, to the drug discovery scientists to facilitate the synthesis and development of novel ALR2 inhibitors that may serve as lead molecules for the treatment of diseases related to the ALR2 enzyme.

Pharmacophore based drug design and synthesis of oxindole bearing hybrid as anticancer agents.

Dual TK inhibitors have shown significant clinical effects against many tumors, but with unmanageable side effects. Design approach and selectivity of these inhibitors plays substantial role in their potency and side-effects. Understanding the homology of binding sites in targeted receptors, and involvement of signaling proteins after the inhibition might help in producing less toxic but effective inhibitors. Herein, we designed benzylideneindolon-2-one derivatives based on homology modeling in binding sites of VEGFR-2 and EGFR receptors as dual- inhibitor potent anticancer compounds with high selectivity. The benzylideneindolon-2-one derivatives were found to possess conformational switch in form of oxindole, substituted at 2-benzimidazole. Within synthesized compounds, 5b was found most active in in-vitro enzyme inhibition assay against VEGFR-2 and EGFR with highest IC50 value of 6.81 ± 2.55 and 13.04 ± 4.07 nM, respectively. Interestingly, cytotoxicity studies revealed selective toxicity of compound 5b against proliferation of A-431 cell lines (over expressed VEGFR-2 and EGFR) with GI50 value of 0.9 ± 0.66 µM. However, the compounds showed mild to moderate activity in all other cancer cell line in the range of 0.2-100 µM. Further mode of action studies by flow cytometry and western blot on A-431 indicated that they work via apoptosis at S- phase following Bcl/Bax pathway, and cell migration via MMP9. 5b not only suppressed tumor growth but also improved vandetanib associated with weight loss toxicity. Moreover, 5b was found safer than sunitinib and erlotinib with LD50 of 500 mg/kg body weight. These results propose 5b as potential anti-tumor drug with safer profile of conventional inhibitors of VEGFR-2 and EGFR for solid tumors.

Advances in 2-substituted benzothiazole scaffold-based chemotherapeutic agents.

Targeted therapy plays a pivotal role in cancer therapeutics by countering the drawbacks of conventional treatment like adverse events and drug resistance. Over the last decade, heterocyclic derivatives have received considerable attention as cytotoxic agents by modulating various signaling pathways. Benzothiazole is an important heterocyclic scaffold that has been explored for its therapeutic potential. Benzothiazole-based derivatives have emerged as potent inhibitors of enzymes such as EGFR, VEGFR, PI3K, topoisomerases, and thymidylate kinases. Several researchers have designed, synthesized, and evaluated benzothiazole scaffold-based enzyme inhibitors. Of these, several inhibitors have entered various phases of clinical trials. This review describes the recent advances and developments of benzothiazole architecture-based derivatives as potent anticancer agents.

Emergence of promising novel DPP-4 inhibitory heterocycles as anti-diabetic agents: A review.

Diabetes has turned out to be an epidemic in the recent years all over the world, and today it has become a burden on the healthcare system. Over the years, with technological advancements, different classes of antidiabetic medications have emerged, like sulfonylureas, biguanides, alpha-glucosidase inhibitors, and thiazolidinediones, but these are often loaded with serious aftermaths like hypoglycemia, weight gain, cardiovascular and renal issues. Dipeptidyl peptidase-4 (DPP-4) inhibition is an exciting and new approach in the treatment of type-2 diabetes. DPP-4 inhibitors or "gliptins" are weight neutral, pose lesser risk of hypoglycemia, and provide a long-term post-meal glycemic control. In this review, an attempt has been made to investigate novel potential compounds that can be added to the existing list of anti-diabetic drugs.

Anterior Esthetic Rehabilitation with Computer-Aided Design/Computer-Aided Manufacturing Zirconia: A Case Report.

In layered zirconia prosthesis, the choice of zirconia composition, framework design, and shade is closely related to the properties of the abutments. This interdependence emphasizes how crucial it is to take a deliberate and tailored approach to meet the unique needs of every therapeutic circumstance. To successfully treat anterior teeth and achieve restorations that look natural, challenges such as incorrect size and shape, atypical gingival contour, and unsightly hues need to be resolved. Ceramodetal restorations have occasionally allowed for the most appealing, authentic replication of natural teeth, despite its proven strength, endurance, and improved aesthetics. Due to their superior cosmetic results, metal-free materials have been used for anterior rehabilitation. Materials like dental zirconia, which offers excellent aesthetics and desired mechanical characteristics, have emerged in response to the increased need for visually appealing and metal-free alternatives. In this case study context, experiences in the clinic using multilayer zirconia prostheses intended exclusively for anterior teeth are discussed.

Using Laser Therapy and Topical Ozone as an Effective Intervention to Revolutionize Denture Stomatitis Treatment: A Case Report.

In dentistry, denture stomatitis (DS), a frequent inflammatory illness of the oral mucosa mostly related to denture wearing, is a major concern. DS is a common oral mycotic infection for those who wear partial or total dentures. The most often found species of Candida that may be isolated from both healthy and diseased oral tissues is Candida albicans. DS is associated with uneven denture surfaces, inadequate oral hygiene, or ill-fitting dentures. The diagnosis and management of DS in a 72-year-old male patient is presented in this case study. The patient complained about burning in his palate and having difficulty chewing. Upon clinical examination, erythema and inflammation were seen in the palate region. The history and clinical findings were consistent with DS. The patient was told to completely stop using dentures. Interventions were included in the treatment plan, such as diode laser therapy, topical ozonated oil application, and teaching about denture hygiene. The third day's follow-up visit revealed a progressive healing of the lesions and symptom relief. The lesion fully resolved on the sixth day. This case emphasizes the value of all-encompassing management techniques in treating DS successfully. It also highlights the significance of patient education, good oral hygiene, and focused therapy in producing favorable results.

Rehabilitating Long Edentulous Span by Using Pier Abutment as a Non-rigid Connector: A Case Report.

An abutment having edentulous space on both sides is referred to as a pier abutment. The rehabilitation of a patient whose primary concern when they first came to the hospital was missing teeth is discussed in this case report. When using a pier abutment for a fixed dental prosthesis, there is a problem with fulcrum and torqueing pressures at the intermediate abutment. Forces on the pier abutment may become localized as a result of using a rigid connector. It has been suggested that non-rigid connectors be used to overcome this. Here, using a non-rigid connector as a stress breaker resulted in less stress being placed on the prosthetic assembly and abutment. This article offers a clinical case report that details the use of a non-rigid connector in a pier abutment scenario for rehabilitation.

Less Is More: A Case Report on All-on-4 Prosthesis.

Severe alveolar ridge atrophy following tooth removal poses a common and worsening issue in edentulous jaws, affecting patient comfort and quality of life. The All-on-4 approach involves axially positioning two anterior implants and distally orienting two posterior implants, reducing cantilever length and enabling prostheses with 12 teeth. This less invasive option, utilizing distal tilting of implants at 30°, offers biomechanical advantages and has shown short-term success, though long-term research is limited. Immediate-loading treatments are gaining popularity for their high survival rates. Understanding the biomechanics of implant-supported prostheses is crucial for long-term success, emphasizing the importance of optimal occlusal schemes. Challenges such as bone defects and surgical complexity have led to the exploration of achieving full-arch fixed restorations with fewer implants, building upon Brånemark's early work with four implants. The All-on-4 concept, originating in 1999, proves to be a viable treatment option, providing excellent long-term results and improved load distribution in challenging clinical circumstances. This case report explores the successful rehabilitation of a jaw using the All-on-4 implant prosthesis concept, a technique strategically placing four implants in completely edentulous jaws to support a fixed, immediately loaded prosthesis.

Prosthetic Rehabilitation of All-on-Six Implant-Supported Prosthesis: A Case Report.

This clinical report explores the effectiveness of dental implants for rehabilitating fully edentulous arches, with a focus on the all-on-six treatment approach. Implant-supported fixed restorations, particularly using six implants, are presented as an expected and cost-effective solution for the rapid repair of the edentulous patient, avoiding the need for bone grafting. This report details the successful rehabilitation of a patient's completely edentulous arches using the all-on-six concept, highlighting the meticulous planning and execution involved. It concludes that precise diagnostic and implant planning, along with thorough attention to all the features, is crucial for successful implant-supported fixed prostheses, with the all-on-six concept offering improved clinical and radiological outcomes for atrophied maxillae.

Fabrication of Implant-Supported Auricular Prosthesis Using Artificial Intelligence.

The absence of any organ of the facial region causes an asymmetrical appearance. This asymmetrical appearance can cause social dilemmas for the patient. The maxillofacial technician, the prosthodontist, and the patient must work closely together to fabricate an epithesis. On the implants, a superstructure is first constructed. Most of it is made up of rings and a bar that joins the implants. The firm acrylic resin base of the epithesis is equipped with clips that serve as the epithesis's retention mechanism. The actual epithesis is made of silicone rubber. The epithesis has to be shaped and colored with extreme caution. An appropriate substitute is an auricular prosthesis that is implant-retained. Microtia, deformity, malformation, and loss of the external ear, either partially or completely, can result from a variety of inherited genetic conditions. To evaluate the symmetry of both ears, artificial intelligence (AI) software is used. An Instagram lens Gridset by crystalwavesxx was used to correct and verify the bilateral symmetry of the patient. This case report primarily focuses on the fabrication of implant-supported auricular prostheses using AI.

Anterior Palatal Radicular Cyst: A Case Report.

The most prevalent kind of odontogenic cysts is radicular cysts, which usually develop from the epithelial remnants in the periodontal ligament as a result of inflammation that follows pulp necrosis. We report a case of a 49-year-old male patient who complained of painless swelling in the maxillary anterior region, which turned out to be a radicular cyst. Upon clinical examination, a soft, nontender swelling that fluctuated was found. A periapical lesion was found upon radiographic assessment. A radicular cyst was tentatively diagnosed based on clinical and radiological features. The treatment plan included enucleation, restoration of the defect with bone graft, and endodontic therapy with antibiotics. Endodontic therapy was administered after the cystic lesion was surgically removed. The diagnosis of a radicular cyst was validated by histopathological analysis. The significance of a multidisciplinary approach for the successful management of radicular cysts is emphasized in this case report, which also underscores the need for a comprehensive clinical and radiographic evaluation for accurate diagnosis. Prompt identification and suitable intervention are essential to avert possible complications and guarantee successful treatment results.

Basal Implant Placement in the Anterior Aesthetic Zone: A Case Report.

Aesthetics are one of the primary goals of restorative care. Teeth that are traumatized in the anterior maxilla usually avulse or require extraction due to fractures. Rehabilitation is challenging in such a therapeutic state since it presents several anatomical and aesthetic issues. There are circumstances in which traditional implant placement is problematic. There must be enough bone for implant placement to be uneventful and successful. Other surgical therapies may be necessary in addition to implant placement for certain operations, such as extensive grafting, direct or indirect sinus lifts, and nerve lateralization. Certain procedures are required for these operations but are not always achievable. Because single-piece basal implants provide immediate temporization and loading while receiving adequate anchoring from the basal cortical bone, they have been extensively used to rehabilitate resorbed ridges. This case report demonstrates the placement of the basal implant in the anterior zone.

Sustainable Dentistry: A Comprehensive Review of the Recycling Techniques for Gypsum Products in Prosthodontics.

This review explores the pivotal role of sustainable dentistry with a specific focus on the recycling of gypsum products in prosthodontics. As oral health practices increasingly impact the environment, the adoption of sustainable approaches becomes imperative. The review delves into the environmental challenges posed by gypsum waste in prosthodontics and examines current recycling techniques, presenting key findings and successful case studies. The call to action is directed towards the dental community, urging practitioners, educators, and policymakers to prioritize sustainable practices, encompassing responsible waste management and the incorporation of eco-friendly materials. Looking to the future, the review envisions a promising landscape for sustainable dentistry in prosthodontics, propelled by emerging technologies and a collective commitment to environmentally conscious oral healthcare. Ultimately, this review serves as a catalyst for positive change, advocating for a transformative shift toward sustainability within the dental community.

Precursor engineering for soft selective synthesis of phase pure metal-rich digenite (Cu9S5) and djurleite (Cu31S16) nanocrystals and investigation of their photo-switching characteristics.

Copper sulfide nanostructures have evolved as one of the most technologically important materials for energy conversion and storage owing to their economic and non-toxic nature and superior performances. This paper presents a direct, scalable synthetic route aided by a single source molecular precursor (SSP) approach to access copper sulfide nanomaterials. Two SSPs, CuX(dmpymSH)(PPh3)2 (where X = Cl or I), were synthesized in quantitative yields and thermolyzed under appropriate conditions to afford the nanostructures. The analysis of the nanostructures through pXRD, EDS and XPS suggested that phase pure digenite (Cu9S5) and djurleite (Cu31S16) nanostructures were isolated from -Cl and -I substituted SSPs, respectively. The morphologies of the as-synthesized nanomaterials were investigated using electron microscopy techniques (SEM and TEM). DRS studies on pristine materials revealed blue shifted optical band gaps, which were found to be optimum for photoelectrochemical application. A prototype photoelectrochemical cell fabricated using the pristine nanostructures exhibited a stable photo-switching property, which presents these materials as suitable economic and environmentally friendly photon absorber materials.

LiAlO2:Gd-Based Versatile and Ultrasensitive Detector for Gamma and Neutrons by Thermal and Optical Stimulation.

Considering the low-level dose detection requirement for neutron and γ radiation in cancer therapy, synthesis and exploratory studies have been performed on a newly developed phosphor LiAlO2:Gd. Our results reveal that the presence of both Li and Gd makes it sensitive to both gamma and thermal neutrons. The applicability of LiAlO2:Gd for beta, gamma, and neutrons in both thermally stimulated and optically stimulated modes has been verified by extensive experiments followed by kinetic parametric evaluation with theoretical calculations. The current work confirms that LiAlO2:Gd is a highly sensitive phosphor with a minimum detectable dose of 5.7 µSv for gamma and 92 µSv for themral neutrons. The phosphor is found to show very high sensitivity at low energy and dose. Its ability for detection and discrimination of both gamma and thermal neutrons makes it a potential material to be used in medical dosimetry.

Effectiveness, Esthetics, and Success Rate of Dental Implants in Bone-Grafted Regions of Cleft Lip and Palate Patients: A Systematic Review and Meta-Analysis.

Congenital clefts impair function and appearance, thus impacting a patient's social and mental health. A multidisciplinary team that can offer comprehensive treatment from infancy through maturity and beyond can successfully address these abnormalities. Dental rehabilitation is very important for these patients; these abnormalities should be identified and must be treated accordingly. Hence it is of utmost importance to know the success rate and changes in quality of life from patient satisfaction in order to plan future treatment goals when coming across such cases. The aim of this article is to determine success rate, esthetics, and patient satisfaction in implant-based oral rehabilitation in bone-grafted regions of cleft patients. Registration was carried out in PROSPERO (International Prospective Register of Systematic Review) with registration number CRD42022329861 on May 7, 2022. Medical Subject Headings (MeSH) terms such as cleft lip, cleft palate, survival rate, and dental implants were used to handpick articles via an electronic database. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to compile all the data gathered from an electronic database. According to the collected data, 93.5% of the survival rate with dental implants was noted irrespective of the type of bone grafts used. Also, improvement in quality of life was achieved in these patients. Effectiveness, esthetics, and success rate are very well achievable with implants in cleft patients. Although the aesthetics are not equivalent to that of dental implants in normal patients, patient satisfaction is still satisfactory in patients with dental implants in bone-grafted regions of cleft lip and palate.

Revolutionizing Maxillofacial Rehabilitation for Ocular Defects: The Impact of Three-Dimensional Printing and Sublimation Transfer Technique on Changing Horizons.

An absence or any disfigurement to the eye leads to psychological handicap for the patient. An ocular defect is a defect of an eye because of a cyst, road traffic accident, or enucleation of an eye due to infection. While correcting this type of defect, maxillofacial prosthodontists should consider all aspects such as esthetics, comfort, and functions of the ocular prosthesis, which gives a lifelike appearance to the prosthesis. A prosthetic eye wearer patient complained of asymmetry and opaque appearance of the ocular prosthesis. The patient had lost his eye in a road traffic accident and has been wearing a prosthesis for 8-12 months but is not pleased with how the prosthesis looks. A novel prosthesis created by the use of sublimation transfer technology and three-dimensional printing to improve the esthetics exactly replicates the contralateral normal eye. In a proposed case report, an algorithm for the fabrication of customized ocular prostheses was improved. A smooth blend of conventional as well as digital methods is used to optimize the results.

Rehabilitation of Malpositioned Implant in the Anterior Region With Customized Abutment.

The misplacement of implants represents an unfavorable complication in dental implant prostheses. Numerous instances necessitating restorative intervention, colloquially termed "rescue cases," encompass either novel occurrences or reconstructions of irreversible implant scenarios. A viable solution for addressing these prosthesis-related challenges is using cementable options. This issue is directly linked to improperly placed implants, which dentists find challenging to rectify due to the absence of angle-correcting abutments from manufacturers. In such situations, the preferred treatments involve either Implant Innovations' universal castable long abutment (UCLA) (Palm Beach Gardens, Florida, United States) or a customized abutment fashioned from the titanium alloy impression coping for the Core-Vent implant (Paragon, Calabasas, California, United States). The Department of Prosthodontics received a referral for a patient with an anterior implant that had been misplaced and required rehabilitation. This case report outlines the chosen treatment approach for an implant situated buccally.

Unveiling the Realm of Denture Fabrication: Revitalizing Aesthetics and Optimizing Efficiency for Geriatric Patients.

Disfigurement of the face has a significant impact not only on the appearance and function but also on the psychological well-being of an individual. Due to tooth loss, various psychological problems can occur. Dentures can help patients regain a sense of normalcy and also boost their confidence to live in society. Complete denture restores phonetics, esthetics, and mastication. A 63-year-old male patient reported to the Department of Prosthodontics with the chief complaint of total loss of teeth and wanted to get treated for the same. The purpose of this article is to describe changes in impression techniques, dental material, methodologies in teeth setting, and novel approaches to enhance the esthetics to optimize the results in a final complete denture. To reestablish the patient's masticatory, apparatus steps of complete denture fabrication were revisited accompanied by the modern application of innovative techniques with the base of historical concept.

Developmental and adult acclimation impact cold and drought survival of invasive tropical Drosophila kikkawai.

Narrow distribution patterns of tropical Drosophila species are limited by lower resistance to cold or drought. In the invasive tropical Drosophila kikkawai, we tested whether developmental and adult acclimations at cooler temperatures could enhance its stress resistance level. Adult acclimation of winter collected body color morphs revealed a significant increase in the level of cold resistance. For light morph, its abundance during winter is not consistent with thermal-melanism hypothesis. However, higher cold acclimation capacity, as well as storage of energy metabolites could support its winter survival. In the wild-caught light and intermediate morphs, there is a lack of trade-off between cold and heat resistance but not in the case of dark morph. Developmental plasticity (15°C) resulted in the fivefold increase of cold survival at 0°C; and a twofold increase in desiccation resistance but a modest reduction (∼28-35%) in heat resistance as compared to morph strains reared at 25°C. Drought acclimation changes were significantly higher as compared with cold or heat pretreatment. We observed a trade-off between basal resistance and acclimation capacity for cold, heat, or drought resistance. For homeostatic energy balance, adult acclimation responses (cold versus drought; heat versus drought) caused compensatory plastic changes in the levels of proline or trehalose (shared patterns) but different patterns for total body lipids. In contrast, rapid cold or heat hardening-induced changes in energy metabolites were different as compared to acclimation. The ability of D. kikkawai to significantly increase stress tolerance through plasticity is likely to support its invasion potential.