Sulforaphane inhibits histone deacetylase causing cell cycle arrest and apoptosis in oral squamous carcinoma cells.

Background: Biologic compounds have recently generated interest in cancer chemoprevention. Sulforaphane (SFN), an isothiocyanate from cruciferous vegetables, has profound epigenetic actions. Since epigenetic aetiology is crucial for oral cancer, this study evaluated the role of SFN in oral cancer prevention. Methods: Oral squamous cell carcinoma cells (UPCI-SCC-172) were treated with SFN in three concentrations: 10 µM, 20 µM and 30 µM for two time periods: 24 h and 48 h. MTT assay assessed cell proliferation. Histone deacetylase (HDAC) enzyme activity was colorimetrically estimated in the nuclear extracts. Flow cytometry determined cell cycle stages, reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) changes. Extrinsic and intrinsic apoptotic pathways were evaluated from caspase enzyme assays. Results: Cell proliferation and HDAC activity (44% in 24 h and 40% in 48 h) were significantly inhibited (p < 0.01). For 10 µM concentration, G2/M cell cycle arrest was found with a reduction in G1 phase cell population at 24 h and 48 h. Concentrations of 20 µM and 30 µM SFN presented cells in apoptosis marked by increased sub G1 cells at 48 h. Concentrations of 10 µM and 20 µM SFN showed a 1.3 to 2.8-fold increase in ROS generation at 24 h and 48 h. The concentration of 30 µM SFN showed a drop in ROS production, denoting cells already in apoptosis. Fall in MMP was also dose- and time-dependent. Caspase enzyme assays (p < 0.001) demonstrated activation of both extrinsic and intrinsic apoptotic pathways. Conclusion: Inhibitory action of SFN on oral cancer cell proliferation and HDAC activity led to cell cycle arrest and apoptosis. These effects marked by increase in ROS, a decrease in MMP and activation of apoptotic pathways offer exciting therapeutic options.

Mitochondrial Ca2+ overload due to altered proteostasis amplifies apoptosis in C2C12 myoblasts under hypoxia: Protective role of nanocurcumin formulation.

Severe hypoxia triggers apoptosis leads to myofibers loss and is attributable to impaired intracellular calcium (iCa2+ ) homeostasis, resulting in reduced muscle activity. Hypoxia increases intracellular Ca2+ by activating the release of Ca2+ from iCa2+ stores, however, the effect of increased [iCa2+ ] on the mitochondria of muscle cells at high-altitude hypoxia is largely unexplored. This study examined mitochondrial Ca2+ overload due to altered expression of mitochondrial calcium uptake 1 (MICU1), that is, a gatekeeper of the mitochondrial Ca2+ uniporter, impaired mitochondrial membrane potential (ΔΨm). p53 stabilization and its translocation to the mitochondria were observed following disrupted mitochondrial membrane integrity in myoblasts under hypoxia. Furthermore, the downstream effects of p53 led to the upregulation of proapoptotic proteins (Bax, Caspase-3, and cytochrome C) in myoblasts under hypoxia. Nanocurcumin-pyrroloquinoline quinone formulation (NCF; Indian patent no. 302877), developed to address hypoxia-induced consequences, was found to be beneficial in maintaining mitochondrial Ca2+ homeostasis and limiting p53 translocation into mitochondria under hypoxia in muscle myoblasts. NCF treatment also modulates heat shock proteins and apoptosis-regulating protein expression in myoblasts. Conclusively, we proposed that mitochondrial Ca2+ overload due to altered MICU1 expression intensifies apoptosis and mitochondrial dysfunctionality. The study also reported that NCF could improve mitochondrial [Ca2+ ] homeostasis and antiapoptotic ability in C2C12 myoblasts under hypoxia.

The association of screen time with intake of potentially cariogenic food and oral health of school children aged 8-14 years-a cross-sectional study.

This study aimed to test the hypothesis that excessive screen time can affect the oral health of school children. In this observational cross-sectional study conducted in four schools in Delhi, National Capital Region (NCR), India, 497 school children aged 8-14 years were included. Convenience sampling was used to select schools. Data were extracted from a questionnaire pertaining to screen time and dietary habits, which was distributed to the school children during their first planned school visit. Seven days later, on their second school visit, the children were clinically examined by a calibrated examiner (κ = 0.9) for dental caries, plaque and gingival health using the following indices: Decayed, Missing, Filled teeth (DMFT)/decayed, extracted, filled teeth (deft), Silness-Loe plaque index (PI) and Loe-Silness gingival index (GI), respectively. Overall, 88.7% of the participants exhibited screen time of ≥2 h with maximum frequency for smartphones (93%), followed by television (84.7%). Significantly higher DMFT/deft values (3.20 ± 0.68 vs. 2.45 ± 0.35, p = 0.001), PI (1.04 ± 0.21 vs. 0.33 ± 0.10, p < 0.001) and GI (1.45 ± 0.34 vs. 0.12 ± 0.04, p < 0.001) were observed in those with screen time ≥2 h as compared to those with screen time <2 h. Data underwent statistical analysis with a significance threshold of p < 0.05. Excessive screen time can influence the eating patterns of children and contribute to higher DMFT, GI and PI.

Control of Anxiety in Pediatric Patients using "Tell Show Do" Method and Audiovisual Distraction.

INTRODUCTION: Visiting a dentist can easily evoke strong fear reactions and acute anxiety in children. It is one of the most basic reasons for avoidance and neglect of dental care. It may obstruct delivery of dental care, as the child may be unwilling to accept the treatment being provided by the dentist. AIM: To evaluate and compare reduction in anxiety level in patients undergoing dental treatment at first dental visit. TECHNIQUE: The study was conducted on 400 patients coming to the Department of Pedodontics and Preventive Dentistry, Guru Teg Bahadur Hospital, University College of Medical Sciences, New Delhi, for their first dental visit. Anxiety was recorded using facial image scale (FIS), Venham's picture test (VPT), blood pressure, pulse rate (PR), and oxygen saturation (SpO2) at different stages of the visit. Patients coming for the first dental visit were subjected to restorative treatment under Tell show do (TSD) method and audiovisual distraction (AVD). The data collected were tabulated and subjected to statistical analysis. CONCLUSION: The AVD was found to be more capable in reducing anxiety than TSD. Combination of TSD and AVD had an additive effect in reduction of anxiety level and it proved to be more beneficiary. CLINICAL SIGNIFICANCE: If a child's behavior in the dental office cannot be managed, then it is difficult to hold out any dental treatment that is needed. Bringing positivity in the child's behavior would not only increase efficiency of work but would also make the experience for child undergoing treatment more pleasant.

Activator protein-1 (AP-1): a bridge between life and death in lung epithelial (A549) cells under hypoxia.

Activator protein-1 (AP-1) transcription factor plays a central role in hypoxia to modulate the expression of genes that decides the fate of the cell. The aim of the present study was to explore the role of AP-1 subunits in lung epithelial (A549) cells under hypoxia. Cell cycle studies by flow cytometry indicated that cell viability was unaffected by the initial hypoxia exposure (0.5% O2 at 37 °C) for 6 and 12 h. However, both transient cell cycle arrest and cell death was detected at 24 and 48 h. Flow cytometry and spectrofluorometry data confirmed the increase in ROS levels. Elevated ROS and calcium levels activated the stress-related MAPK signaling cascade. ERK and JNK were activated in early hypoxic exposure (within 6 h), whereas p38 were activated in 48 h of hypoxia. These subtypes further stimulated the subunits of AP-1 at different times of hypoxia exposure to orchestrate different genes responsible for cell proliferation (6 and 12 h) and apoptosis (24 and 48 h). Our results clearly depict the role of AP-1 heterodimer, i.e., p-c-jun/c-fos, p-c-jun/fosB, junD/c-fos, and junD/fosB in cell proliferation/survival by regulating the expression of Bcl-2 and cyclins (D1 and B1) at 6 h and 12 h of hypoxia, whereas junB/Fra-1 heterodimer have important role in apoptosis by regulating the expression of p53, Bax, and cyclin-dependent kinase inhibitors (p16, p21, p27) at 24 h and 48 h of hypoxia. Also, the cell survival signaling pathway NO-AKT interrupted at 24 h and 48 h of hypoxia indicating cell death. In conclusion, hypoxia for different time points activated different subunits of AP-1 that combined to form different heterodimers. These dimers regulated the expression of genes responsible for cell proliferation and apoptosis. Since, AP-1 plays a role in the decisive phenomenon of the cell to choose between proliferation and apoptosis; thus, its subunits or dimers could be a good therapeutic target for many diseases.

Mean frequency and relative fluorescence intensity measurement of γ-H2AX foci dose response in PBL exposed to γ-irradiation: An inter- and intra-laboratory comparison and its relevance for radiation triage.

Measurement of γ-H2AX protein changes in the peripheral blood lymphocytes (PBL) of individuals exposed to ionizing radiation is a simple, sensitive, and rapid assay for radiation triage and early marker of dose estimation. The qualitative and quantitative measurements of the protein changes were examined using flow cytometry and microscopy. Whole blood and isolated lymphocytes were exposed in vitro between 0.1 and 5 Gy doses of (60) Co γ-radiation at a dose rate of 1 Gy/min. Radiation induced γ-H2AX foci frequency (n = 3) and relative fluorescence intensity (n = 7) in PBL was measured at 0.5 and 2 hrs postexposure. The observed dose response for γ-H2AX foci frequency at both time points, for whole blood and isolated lymphocytes did not show any significant (P > 0.05) differences. However, when compared with γ-H2AX foci frequency scored manually (microscopy), the semiautomated analysis (captured images) showed a better correlation (r(2) = 0.918) than that obtained with automated (Metafer) scoring (r(2) = 0.690). It is noteworthy to mention that, the γ-H2AX foci frequency quantified using microscopy showed a dose dependent increase up to 2 Gy and the relative fluorescence intensity (RFI) measured with flow cytometry revealed an increase up to 5 Gy in the PBL exposed in vitro. Moreover, a better correlation was observed between the γ-H2AX foci frequency obtained by manual scoring and RFI (r(2) = 0.910). Kinetic studies showed that the γ-H2AX foci remain more or less unchanged up to 4 hrs and reduces gradually over 48 hrs of postexposure at 37°C. Further, inter and intra-laboratory comparisons showed consistency in the scoring of γ-H2AX foci frequency by manual and semiautomated scoring. The overall results suggest that measurement of γ-H2AX (microscopy and flow cytometry) should be employed within 4 to 6 hrs for a reliable dosimetry either by sharing the work load between the laboratories or investing more manpower; however, triage can be possible even up to 48 hrs of postirradiation.

Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells.

BACKGROUND: Cancer cells exhibit increased glycolysis for ATP production (the Warburg effect) and macromolecular biosynthesis; it is also linked with therapeutic resistance that is generally associated with compromised respiratory metabolism. Molecular mechanisms underlying radio-resistance linked to elevated glycolysis remain incompletely understood. METHODS: We stimulated glycolysis using mitochondrial respiratory modifiers (MRMs viz. di-nitro phenol, DNP; Photosan-3, PS3; Methylene blue, MB) in established human cell lines (HEK293, BMG-1 and OCT-1). Glucose utilization and lactate production, levels of glucose transporters and glycolytic enzymes were investigated as indices of glycolysis. Clonogenic survival, DNA repair and cytogenetic damage were studied as parameters of radiation response. RESULTS: MRMs induced the glycolysis by enhancing the levels of two important regulators of glucose metabolism GLUT-1 and HK-II and resulted in 2 fold increase in glucose consumption and lactate production. This increase in glycolysis resulted in resistance against radiation-induced cell death (clonogenic survival) in different cell lines at an absorbed dose of 5 Gy. Inhibition of glucose uptake and glycolysis (using fasentin, 2-deoxy-D-glucose and 3-bromopyruvate) in DNP treated cells failed to increase the clonogenic survival of irradiated cells, suggesting that radio-resistance linked to inhibition of mitochondrial respiration is glycolysis dependent. Elevated glycolysis also facilitated rejoining of radiation-induced DNA strand breaks by activating both non-homologous end joining (NHEJ) and homologous recombination (HR) pathways of DNA double strand break repair leading to a reduction in radiation-induced cytogenetic damage (micronuclei formation) in these cells. CONCLUSIONS: These findings suggest that enhanced glycolysis generally observed in cancer cells may be responsible for the radio-resistance, partly by enhancing the repair of DNA damage.

Angiogenesis Inhibitor Drug-induced Benign Migratory Glossitis in a Patient of Juvenile-onset Recurrent Respiratory Papillomatosis under Maintenance Therapy.

Background: Benign migratory glossitis or geographic tongue is a chronic recurring inflammatory condition of the oral cavity. With its ephemeral characteristics, there has been reported literature showing its association with the administration of certain drugs including angiogenesis inhibitors. The antiangiogenic drugs act by selectively inhibiting the vascular endothelial growth factor (VEGF) signaling. It has been widely used as an adjunct and a maintenance agent for the treatment of various cancers. Aims: This study aims to report probable characteristic oral mucosal changes in a patient with juvenile-onset recurrent respiratory papillomatosis (JORRP) under maintenance therapy with an antiangiogenesis drug. Case description: The patient was presented with a burning sensation on having spicy food. This occurred after the completion of three cycles of bevacizumab infusion. It was associated with the appearance of migratory lesions over the tongue and evolved periods of remission and exacerbation. Clinical examination revealed lesions characteristic of the geographic tongue on the anterior two-thirds of the dorsal surface as well as the lateral surface of the tongue classified as type 2, according to Hume criteria. Oral examination revealed dental caries in relation to 52, 54, 62, 63, 74, and 85 teeth and grossly decayed 64. Topical lignocaine gel was instituted for symptomatic relief of the lesion. Full mouth rehabilitation with preventive and restorative therapeutic interventions was carried out. Clinical significance and conclusion: The documented literature along with this report put forth a probable association of geographic tongue with the use of bevacizumab drugs which requires further detailed studies. These lesions generally require symptomatic treatment with assurance only. The etiology is poorly understood. How to cite this article: Kalra N, Tyagi R, Khatri A, et al. Angiogenesis Inhibitor Drug-induced Benign Migratory Glossitis in a Patient of Juvenile-onset Recurrent Respiratory Papillomatosis under Maintenance Therapy. Int J Clin Pediatr Dent 2024;17(1):92-96.

Evidence-based analysis of multi-pronged approaches for education and behavior management of autistic patients in a dental setting.

BACKGROUND: Autism spectrum disorder is a neurodevelopmental condition which has posed a challenge to carers, pediatricians and dentists through the years. Over the last four decades, the disorder has been better understood and management techniques have evolved. In the field of dentistry, the autistic child presents difficulty in management, even for the simplest dental procedures. A comprehensive understanding of other psychoeducational and behavioral approaches to manage autism is very important. This article aims to introduce various important key techniques such as Applied Behavior Analysis, TEACCH, Sensory Adapted Dental Environment, Picture Exchange Communication System, and Animal Assisted Therapy and analyze their application in dentistry. METHODS: A search of literature was carried out in Clinicaltrials.gov, Medline and Scopus with the search terms "Applied Behavior Analysis," "TEACCH," "Sensory Adapted Dental Environment," "Picture Exchange Communication System," and "Animal Assisted Therapy" along with "autism OR autistic," "dental OR dentistry OR oral health." After the screening for inclusion and exclusion criteria, 10 eligible articles were included, in English, published within the last 10 years. RESULTS: Limited research was available regarding these lesser-known behavioral approaches in dentistry. The few that were available showed encouraging results. The different techniques proved useful in increasing acceptance of dental treatment and reducing behavioral disturbances. The patients experienced reduced dental anxiety, lesser discomfort, improved communication, and knowledge. CONCLUSION: Pediatric and special care dentists are likely to benefit by incorporating the recommended comprehensive behavior management techniques in their practice. There is evidence that these techniques will reduce behavioral disturbances in autistic children thereby making primary dental care possible without the need for sedation or general anesthesia.

Management of anxiety using eye movement desensitization and reprocessing therapy in children undergoing extraction: a randomized controlled pilot study.

Background: Eye movement desensitization and reprocessing (EMDR) therapy has been reported to be very efficacious for treating post-traumatic stress disorder (PTSD) and other anxiety-related conditions. However, a review of the literature reveals the sparse use of this therapy in the field of pediatric dentistry. This study aimed to evaluate anxiety trends in pediatric dental patients during local anesthesia and extraction with and without EMDR therapy. Methods: Children in the age range of 8-12 years who required dental extractions were assigned randomly into two groups: an EMDR group (group 1) and a routine behavior management therapy group (group 2; receiving more traditional interventions such as tender love and care behavioral modeling, and distraction). Anxiety scores were recorded at four levels using the visual facial anxiety scale (VFAS) preoperatively, after therapy, after the administration of local anesthesia (LA), and after extraction. Results: Reduced anxiety was observed after the delivery of EMDR therapy, after LA administration, and post-extraction in the EMDR group compared to pre-operative anxiety scores of anxiety (P < 0.001; unpaired Student's t and Mann-Whitney U tests). In the control group, mild reductions in anxiety after routine behavior management therapy were observed, accompanied by spikes in anxiety levels after LA and extractions. Conclusion: EMDR therapy was found to be valuable for reducing anxiety among pediatric dental patients during tooth extraction procedures.

A Rare Case of Autoimmune Polyendocrinopathy-candidiasis-ectodermal Dystrophy Syndrome: Dental Perspective on Diagnosis and Management.

Aim: To report a unique case of Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a young boy and discuss the oral health impact and management of the disease. Background: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder with various clinical manifestations. Biallelic mutations in the autoimmune regulator (AIRE) gene lead to impairment of central immune tolerance and a targeted attack on various endocrine and non-endocrine organs. Patients classically suffer from a triad of disorders, including chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenocortical failure (Addison's disease). Results: In recent times, it has been observed that oral manifestations of the disorder, such as enamel hypoplasia, appear early and frequently. Affected individuals require a comprehensive preventive and minimally invasive approach for oral health along with follow-up throughout their lifespan to manage potentially life-threatening disease manifestations. Conclusion: Prompt recognition by a pediatric dentist can facilitate an earlier diagnosis and allow for screening, preventive and therapeutic services. Clinical Significance: To deliver oral health care in an effective and comprehensive manner, clinicians should be able to recognize, diagnose and manage the signs and symptoms of the disease. How to cite this article: Tyagi R, Kalra N, Khatri A, et al. A Rare Case of Autoimmune Polyendocrinopathy-candidiasis-ectodermal Dystrophy Syndrome: Dental Perspective on Diagnosis and Management. Int J Clin Pediatr Dent 2023;16(1):139-146.

Three-dimensional Printing Technology: Patient-friendly and Time-saving Approach for Space Management in an Autistic Child in COVID-19 Times.

Aim and objective: The present case report comprehensively illustrates the use of a novel digital three-dimensional (3D) printed band and loop space maintainer [computer-aided design and computer-aided manufacturing (CAD/CAM)] for the guidance of eruption with their distinctive attribute of reduced chairside time in a home-schooled autistic child. Background: Three-dimensional (3D) printing is a promising and emerging technology in the arena of dentistry based on CAD/CAM. It has led to the production of customized 3D objects or patient-specific prostheses with accurate results achieved in a time-saving manner. 3D printing has been employed in several latitudes of dentistry; however, the applications are few in the field of pediatric dentistry. Case description: The paper describes the space management of an autistic child for the missing mandibular left primary second molar through the novel technique of 3D printed band and loop space maintainer. Clinical significance: The novel technique has definite advantages, including high precision, accuracy, fast production, and reduced patient exposure to dentists and vice versa, which has been the need of the hour since the advent of the coronavirus disease of 2019 (COVID-19) pandemic. Conclusion: Three-dimensional (3D) printing minimizes dental aerosol-generated exposure by decreasing chairside procedural time and minimizing procedural sitting. The cost-benefit analysis, as applied to the Indian scenario, has also been computed, which makes it equally acceptable. Moreover, 3D printing reduces material waste production, offering a greener and environmentally friendly option in the coming years. The future of pediatric dentistry will evolve with signs of progress in the latest materials and technologies. How to cite this article: Yangdol P, Kalra N, Tyagi R, et al. Three-dimensional Printing Technology: Patient-friendly and Time-saving Approach for Space Management in an Autistic Child in COVID-19 Times. Int J Clin Pediatr Dent 2023;16(S-3):S321-S326.

A Rare Case of Shprintzen-Goldberg craniosynostosis syndrome with Hirschsprung disorder: Dental characteristics and its Clinical Management.

Shprintzen-Goldberg syndrome (SGS) is an autosomal dominant syndrome caused by de novo gene mutations. It is characterized by a number of congenital defects such as craniofacial, skeletal, neurological, and connective tissue abnormalities. It is characterized by craniosynostosis and marfanoid features. To our knowledge, approximately 75 shprintzen-goldberg syndrome cases have been documented since it was first described in 1982. Rare cases of shprintzen-goldberg syndrome have been reported in which the mutated gene was inherited from an unaffected parent through their germline cells i.e., egg or sperm cells. This is a case report of a 6-year-old boy with clinically diagnosed Shprintzen-Goldberg Syndrome with Hirschsprung disease. Patient reported with multiple caries and malpositioned teeth. The treatment initiated with awareness about cariogenic foods, oral hygiene instructions and diet counselling. Subsequently, comprehensive rehabilitation was done. Key words:Dental management, Craniosynostosis, Hirschsprung disorder.

Dietary administration of the glycolytic inhibitor 2-deoxy-D-glucose reduces endotoxemia-induced inflammation and oxidative stress: Implications in PAMP-associated acute and chronic pathology.

Pathogen-associated molecular patterns (PAMPs) like bacterial cell wall components and viral nucleic acids are known ligands of innate inflammatory receptors that trigger multiple inflammatory pathways that may result in acute inflammation and oxidative stress-driven tissue and organ toxicity. When dysregulated, this inflammation may lead to acute toxicity and multiorgan failure. Inflammatory events are often driven by high energy demands and macromolecular biosynthesis. Therefore, we proposed that targeting the metabolism of lipopolysaccharide (LPS)-driven inflammatory events, using an energy restriction approach, can be an effective strategy to prevent the acute or chronic detrimental effects of accidental or seasonal bacterial and other pathogenic exposures. In the present study, we investigated the potential of energy restriction mimetic agent (ERMA) 2-deoxy-D-glucose (2-DG) in targeting the metabolism of inflammatory events during LPS-elicited acute inflammatory response. Mice fed with 2-DG as a dietary component in drinking water showed reduced LPS-driven inflammatory processes. Dietary 2-DG reduced LPS-induced lung endothelial damage and oxidative stress by strengthening the antioxidant defense system and limiting the activation and expression of inflammatory proteins, viz., P-Stat-3, NfκΒ, and MAP kinases. This was accompanied by decreased TNF, IL-1ß, and IL-6 levels in peripheral blood and bronchoalveolar lavage fluid (BALF). 2-DG also reduced the infiltration of PMNCs (polymorphonuclear cells) in inflamed tissues. Altered glycolysis and improved mitochondrial activity in 2-DG-treated RAW 264.7 macrophage cells suggested possible impairment of macrophage metabolism and, therefore, activation in macrophages. Taken together, the present study suggests that inclusion of glycolytic inhibitor 2-DG as a part of the diet can be helpful in preventing the severity and poor prognosis associated with inflammatory events during bacterial and other pathogenic exposures.

Mitigation of radiation injury to reproductive system of male mice by Trichostatin A.

Trichostatin A (TSA), derived from the bacteria Streptomyces hygroscopicus, is a hydroxamic acid having various biological properties such as histone deacetylase inhibition, anticancer and radiomitigative action. However the mitigative activity of TSA against radiation-induced damages in the mouse reproductive system has not yet been elucidated. The present study unraveled the effects of 2 Gy whole body irradiation (60Co γ- radiation) on C57BL/6 mice male reproductive system including structural damages to testes, increase in apoptosis and reduction in germ cell viability, reduced fertility as well as increased genomic instability in the next generation. Moreover, hematological study and micronuclei assay were used to record chances of radiation-induced hematologic cancer and disruption of genomic integrity in F1 generation. Interestingly, TSA administration 1 and 24 h post-irradiation attenuated radiation-induced morphological damage and cellular apoptosis in testes. In male mice, TSA restored hematological parameters and micronuclei frequency to normal levels, restored sperm viability, and helped them overcome radiation-induced temporary sterility 5 weeks after the irradiation. Thus our results showed that TSA reduced the probability of radiation-induced hematologic cancers as well as genotoxicity and restored genomic integrity in the progenies of paternally exposed mice by reducing radiation-induced apoptosis in spermatogenic cells and restoring cell proliferation. This study suggested that TSA could be used as potential radiomitigator for male reproductive system.

Quercetin-3-Rutinoside alleviates radiation-induced lung inflammation and fibrosis via regulation of NF-κB/TGF-ß1 signaling.

BACKGROUND: Radiation exposure to lungs during nuclear catastrophes or radiotherapy poses long-term side effects and can induce pulmonary injury sufficient for causing death. The strategies for preventing or reversing radiation-induced lung injuries have not been yet developed. Quercetin-3-Rutinoside (Q-3-R), a polyphenolic bioflavonoid, has shown multifaceted pharmacological applications due to its high antioxidant and anti-inflammatory properties. PURPOSE: In the current study, the potential of Q-3-R against radiation-induced lung pneumonitis/fibrosis and the possible underlying mechanism was investigated. STUDY DESIGN: To evaluate the effect of Q-3-R against lung damage, C57Bl/6 mice were administered with Q-3-R (10 mg/kg b.wt.) and irradiated with a single dose of gamma radiation (12 Gy) at thoracic region. METHODS: 16 weeks after irradiation lung damage was seen by histopathological studies and staining for collagen deposition. Expression of Nuclear factor kappa-B (NF-κB), transforming growth factor-ß1 (TGF-ß1), Smad3, intercellular adhesion molecule 1 (ICAM-1), α-smooth muscle actin protein (α-SMA), Aquaporin 5 (AQP 5), Interleukins (IL-6, IL-18, IL-1ß), tumor necrosis factor-α (TNF-α) and caspase-3 was evaluated by immunohistochemistry/western blot/Elisa. Reactive oxygen species (ROS)/ Nitric oxide (NO) scavenging potential of Q-3-R and inhibition of cell death in irradiated lungs were also assessed. RESULTS: Mice showed signs of pneumonitis and fibrotic changes in lungs following radiation treatment. A dramatic increase in inflammatory cells and cytokines contributing to lung disease pathogenesis was observed. Furthermore, expression of NF-κB, TGF-ß1, Smad3, ICAM-1, AQP5and α-SMA was found markedly up-regulated. However, pretreatment of Q-3-R significantly attenuated radiation-induced pneumonitis and fibrosis. Histological examination revealed less structural and fibrotic changes with down-regulation of AQP 5, ICAM-1, α-SMA and caspase-3 in Q-3-R pretreated irradiated groups. The formulation significantly relieved lung injury by suppressing inflammatory and pro-fibrotic cytokines such as IL-6, IL-18, IL-1ß, TNF-α and TGF-ß1 via inhibition of NF-κB. Q-3-R also curtailed radiation-induced ROS/NO generation and minimized DNA damage in the irradiated lungs. CONCLUSION: The findings from the current study clearly demonstrate that Q-3-R provides radioprotection to the lungs by regulating NF-κB/TGF-ß1 signaling, scavenging free radicals, preventing perivascular infiltration and prolonged inflammatory cascade which could otherwise lead to chronic radiation fibrosis. Q-3-R can be proved as a potential therapeutic agent for alleviating radiation-induced lung injury in case of planned or unplanned radiation exposure scenario.

In-vitro alleviation of ochratoxin a mediated cytotoxicity using N-acetyl-L-tryptophan glucoside pretreatment.

AIMS: Ochratoxin A (OTA) has been reported to exhibit nephrotoxicity through induction of cell redox homeostasis perturbation, mitochondrial hyperpolarization and depolarization, protein synthesis inhibition, apoptosis, etc. In the present examination, the protective efficiency of novel synthesized molecule, N-acetyl-L-Tryptophan glucoside (NATG) towards OTA prompted toxicity was evaluated using Human Embryonic Kidney (HEK-293) cells. MAIN METHODS & KEY FINDINGS: The cells were treated with NATG (0-200 µg/ml) before OTA treatment (0-20 µg/ml) the and protection efficiency of NATG was evaluated using MTT and SRB assay. OTA-induced intracellular ROS and its inhibition via NATG (10 µg/ml) pre-treatment was evaluated using the 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) probe. Protective effects of NATG pre-treatment on OTA treated cells had been evaluated in terms of oxidative stress, cell cycle perturbations, mitochondrial membrane disturbance and apoptotic modulation through flowcytometry. Results of the study demonstrated that NATG provides significant protection to HEK -293 cells against OTA induced toxicity primarily by reducing oxidative stress, maintaining mitochondrial membrane homeostasis and inhibiting apoptosis. Furthermore, molecular docking study demonstrated that NATG may efficiently bind with OTA binding pocket on phenylalanyl t-RNA synthetase, resulting in inhibiting OTA incorporation within the newly synthesized peptides and therefore may ameliorate OTA mediated protein synthesis inhibition. SIGNIFICANCE: Present study demonstrated a significant protective efficacy of N acetyl-L- tryptophan glucoside (NATG) against OTA induced toxicity in HEK -293 cells. In future, NATG can be developed as a potential protective agent against OTA induced toxicity in humans.

Differences in DNA condensation and release by lysine and arginine homopeptides govern their DNA delivery efficiencies.

Designing of nanocarriers that can efficiently deliver therapeutic DNA payload and allow its smooth intracellular release for transgene expression is still a major constraint. The optimization of DNA nanocarriers requires thorough understanding of the chemical and structural characteristics of the vector-nucleic acid complexes and its correlation with the cellular entry, intracellular state and transfection efficiency. L-lysine and L-arginine based cationic peptides alone or in conjugation with other vectors are known to be putative DNA delivery agents. Here we have used L-lysine and L-arginine homopeptides of three different lengths and probed their DNA condensation and release properties by using a multitude of biophysical techniques including fluorescence spectroscopy, gel electrophoresis and atomic force microscopy. Our results clearly showed that although both lysine and arginine based homopeptides condense DNA via electrostatic interactions, they follow different pattern of DNA condensation and release in vitro. While lysine homopeptides condense DNA to form both monomolecular and multimolecular complexes and show differential release of DNA in vitro depending on the peptide length, arginine homopeptides predominantly form multimolecular complexes and show complete DNA release for all peptide lengths. The cellular uptake of the complexes and their intracellular state (as observed through flow cytometry and fluorescence microscopy) seem to be controlled by the peptide chemistry. The difference in the transfection efficiency of lysine and arginine homopeptides has been rationalized in light of these observations.

Comparative Evaluation of Hand K-flex Files, Pediatric Rotary Files, and Reciprocating Files on Instrumentation Time, Postoperative Pain, and Child's Behavior in 4-8-year-old Children.

BACKGROUND: A pulpectomy is regarded as the choice modality of treatment for necrotic teeth. The use of hand files, though popular traditionally as a gold standard, may be challenging due to increased chairside time. Postoperative pain is one of the most common complications of pulpectomy and may be unpleasant for a child/pedodontist. Rotary files were found to reduce instrumentation time, reduce apical extrusion, and in turn reduce pain but there is a lack of studies in primary teeth particularly for pediatric and reciprocating file systems. The increased number of options available today makes it a dilemma for the operator to choose a suitable file system. AIM AND OBJECTIVE: The study aimed to evaluate and compare the instrumentation time, postoperative pain, and effect on child's behavior among three groups, i.e., hand K-flex files (group I), pediatric rotary files (group II), and reciprocating files (group III). MATERIALS AND METHODS: A total of 75 primary molar teeth after meeting inclusion criteria were randomly allocated into three groups. During the procedure, step-wise instrumentation time was recorded using a stopwatch. The child's behavior pre- and postoperatively was assessed by an evaluator. The postoperative pain (up to 1 week) was assessed by a questionnaire. RESULTS: The mean age of children taken for the study was 6.03 ± 1.2 years with 46 males and 29 females. The mean biomechanical preparation time was observed to be significantly shorter in the pediatric rotary and reciprocating file groups vs hand K-flex files (p < 0.001**). The postoperative pain after 6 hours had a mean value of 0.88 + 0.9 for the hand K-flex file group which was significantly higher than both rotary file groups (p < 0.05*). The pre- and postoperative behavior revealed no significant difference. CONCLUSION: The clinical performance of pediatric and reciprocating files was superior, but the choice of file system did not significantly alter behavior. HOW TO CITE THIS ARTICLE: Tyagi R, Khatri A, Kalra N, et al. Comparative Evaluation of Hand K-flex Files, Pediatric Rotary Files, and Reciprocating Files on Instrumentation Time, Postoperative Pain, and Child's Behavior in 4-8-year-old Children. Int J Clin Pediatr Dent 2021;14(2):201-206.

Comparison of parental satisfaction with strip crowns and primary anterior zirconia crowns in 3-5 years old children over 1 year.

BACKGROUND: During the past decade, parental involvement for the selection of full coronal restorations for the primary anterior teeth of their children has been increased. Two most common anterior aesthetic full coronal restorations, the strip crowns and the preformed zirconia crowns, are available options. AIM: The aim of this study is to compare parental satisfaction with strip crowns and preformed primary anterior zirconia crowns over 1 year in 3-5 years old children. MATERIALS AND METHODS: Forty maxillary primary incisors were restored by either strip crown or zirconia crown in 24 children. Permuted block randomization method was used for the allocation of participants. Twenty-four parents participated were recalled to fill the questionnaire over 1 year. One parent dropped out at the end of 1 year. Data were analyzed using the t-test and Chi-square test. P < 0.05 considered statistically significant. RESULTS: Parents were satisfied with both types of restorations. Statistically significant relationship was found between overall satisfaction and durability (P = 0.004) with strip crowns and with the color (P = 0.043) in the zirconia crowns. The parents with the lower satisfaction levels with the durability of strip crowns and color of zirconia crowns rated high overall satisfaction. CONCLUSION: Parental overall satisfaction was higher for preformed primary anterior zirconia crowns than strip crowns. Almost equal number of parents was satisfied with all other parameters except for durability, which was more for zirconia crowns.