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Goal of the perspective: Stromal cell-derived factor-1 alpha CXCL12/SDF-1 has a substantial impact on the tumorigenicity in tobacco related oral cancer. Inhibition could help derive preventive and therapeutic approaches. Discussion: Binding energy score between CXCL12/SDF-1 and small molecule Hesperetin is indicative of a strong and stable interaction, significative of a high affinity for the chemokine. The specific molecular interactions, including hydrogen bonding and van der Waals interactions further contribute to the stable complex formation. Conclusion: Targeting molecular components of the NF-κB signaling pathway through inhibition of CXCL12/SDF-1 could serve as a vital therapeutic adjunct in management of tobacco associated oral cancer. Also topical drug delivery systems with Hesperetin can be planned in oral potentially malignant disorders.

In this work, sequential batch reactor (SBR) was employed for the treatment of textile dye wastewater. The performance of four white rot fungi (WRF) viz. Coriolus versicolor, Pleurotus floridanus, Ganoderma lucidum and Trametes pubescens was evaluated in pure and mixed combinations in terms of decolorization. From the results it was found that the combination of Pleurotus floridanus, Ganoderma lucidum and Trametes pubescens was best and they were used in the SBR. The process parameters like air flow rate, sludge retention time (SRT) and cycle period were optimized using response surface methodology (RSM). At these optimized conditions, treatment of textile dye wastewater was carried out at various initial dye wastewater concentration and hydraulic retention time. The performance of SBR was analyzed in terms of decolorization, COD reduction and sludge volume index (SVI). From the results it was found that a maximum decolorization and COD reduction of 71.3% and 79.4%, respectively, was achieved in the SBR at an organic loading rate of 0.165 KgCOD/m3 d. The sludge volume index (SVI) was found to be low in the range of 90–103 mL/g. The kinetic study was carried out using a first order based model and the degradation follows the first order system.

The article presents a study which evaluated the variation in fruit morphometric and bio-chemical traits and select superior clones for establishing large scale plantation of tamarind, a multipurpose tree species. The study was conducted in clonal assemblage of tamarind established in randomized complete block design. Significant variations in all the morphology and biochemical characters among the tamarind forms were found.

Midlife is a pivotal stage of adulthood, characterized by biological, psychological, and social transitions that often lead to a “midlife crisis.” This phenomenon, while not universal, manifests as a period of self-reflection, reassessment, and potential turmoil, influenced by personal and societal factors. This paper explores the complexities of midlife, including its impact on mental health, relationships, careers, and overall well-being. Key themes include the transition through ego mastery stages, the interplay of physical health, mortality awareness, and evolving roles, as well as gender-specific experiences. While midlife crises may result in emotional upheaval and dissatisfaction, they also offer opportunities for growth and self-discovery. Coping strategies, such as reframing challenges, seeking support, and prioritizing physical activity, are highlighted as transformative tools. The role of healthcare professionals in normalizing this experience and fostering resilience is emphasized. Ultimately, this study underscores midlife as both a challenging and enriching phase, inviting further research into its nuanced dynamics..

The impact of fat on abdominal compression effectiveness in abdominal cancers was determined using magnetic resonance imaging (MRI). Visceral and subcutaneous fat were delineated on T2W 3D MRI, and motion change with compression was measured on 2D cine MRI. Results from 16 participants showed no correlation between fat percentage, body mass index (BMI), and motion change. Median BMI was 28.7 (SD, 4.9). Mean motion reduction was 7.8 mm (IQR, 5.0; p = 0.001) with compression. While no direct link was found between fat, BMI, and compression effectiveness, abdominal compression remains crucial for motion management in radiotherapy planning, providing dosimetric benefits.

Background: Patients who experience a pelvic cancer recurrence in or near a region that received initial radiotherapy, typically have few options for treatment. Organs at risk (OAR) have often reached their dose constraint limits leaving minimal dose remaining for standard re-irradiation (reRT). However, photon based stereotactic ablative radiotherapy (SABR) has been utilised for reRT with promising initial results although meeting OAR constraints can be challenging. Proton beam therapy (PBT) could offer an advantage. Materials and methods: SABR plans used for treatment for ten pelvic reRT patients were dosimetrically compared to PBT plans retrospectively planned using the same CT and contour data. PBT plans were created to match the CTV dose coverage of SABR treatment plans with V100% ≥95%. An ‘as low as reasonably achievable’ approach was taken to OAR tolerances with consideration of OAR dose from the initial radiation (using equivalent dose in 2 Gy fractions). Results: Dosimetric comparison of relevant OAR statistics showed a decrease in OAR dose using PBT over SABR in all patients, with equivalent target coverage. The largest statistically significant reduction was seen for the colon D0.5 cm3 with a median reduction from 13.1 Gy to 5.9 Gy. There were statistically significant dose reductions in the median dose to small bowel, sacral plexus and cauda equina. Conclusion: PBT has the potential for significant dose reductions for OARs in the pelvic reRT setting compared to SABR. However, it remains unclear if the magnitude of these OAR dose reductions will translate into clinical benefit.

Abstract Background The SCOPE trials (SCOPE 1, NeoSCOPE and SCOPE 2) have been the backbone of oesophageal RT trials in the UK. Many changes in oesophageal RT techniques have taken place in this time. The SCOPE trials have, in addition to adopting these new techniques, been influential in aiding centres with their implementation. We discuss the progress made through the SCOPE trials and include details of a questionnaire sent to participating centres. to establish the role that trial participation played in RT changes in their centre. Methods Questionnaires were sent to 47 centres, 27 were returned. Results 100% of centres stated their departmental protocol for TVD was based on the relevant SCOPE trial protocol. 4DCT use has increased from 42 to 71%. Type B planning algorithms, mandated in the NeoSCOPE trial, were used in 79.9% pre NeoSCOPE and now in 83.3%. 12.5% of centres were using a stomach filling protocol pre NeoSCOPE, now risen to 50%. CBCT was mandated for IGRT in the NeoSCOPE trial. 66.7% used this routinely pre NeoSCOPE/SCOPE 2 which has risen to 87.5% in the survey. Conclusion The results of the questionnaires show how participation in national oesophageal RT trials has led to the adoption of newer RT techniques in UK centres, leading to better patient care.

The article focuses on a study which examines the effectiveness of aided compared to unaided writing skill with special reference to English grammar of X standard students in Thiurvallur District, Tamil Nadu, India. Topics discussed include the accuracy level of students' writing, the ability of the students to patch up their knowledge deficiency when they are supplied with reference materials, and the effect of the educational level of their family members on their English proficiency.

The study aimed to investigate the genetic variability and association of morphological and biochemical characters of 60 different Tamarind clones. The experiment was conducted in 10-year-old germplasm bank of Tamarind at ICFRE-IFGTB Field Research Station, Kurumbapatti, Salem, Tamil Nadu, India. Analysis of variance revealed significant variation among clones for the morphological and biochemical characters. High phenotypic and genotypic coefficients of variation were observed for the parameters like annual yield per tree, fruit weight, pulp weight, seed weight, shell weight, vein weight, number of seeds per fruit, fruit length, fruit thickness, fruit width and total sugar content. High broad-sense heritability and high genetic advance per cent mean were recorded for annual yield per tree, tree height, number of primary branches, fruit weight, pulp weight, seed weight, shell weight, vein weight, number of seeds per fruit, fruit length, fruit thickness, fruit width, ascorbic acid, total acidity, total sugar, reducing sugar, non-reducing sugar and protein. Phenotypic path analysis highlighted positive direct effect of fruit weight, pulp weight and seed weight on annual yield per tree. Mahalanobis D-square analysis clustered the 60 tamarind clones into ten groups with higher inter-cluster distances highlighting the substantial genetic diversity present among the genetic resources. This comprehensive assessment provides insights for the genetic improvement of tamarind, aiding in the selection of superior genotypes for breeding programs.

An effective fusion method for combining information from single modality system requires Multimodal biometric crypto system. Fuzzy vault has been widely used for providing security, but the disadvantage is that the biometric data are easily visible and chaff points generated randomly can be easily found, so that there is a chance for the data to be hacked by the attackers. In order to improve the security by hiding the secret key within the biometric data, a new chaff point based fuzzy vault is proposed. For the generation of the secret key in the fuzzy vault, grouped feature vectors are generated by combining the extracted shape and texture feature vectors with the new chaff point feature vectors. With the help of the locations of the extracted feature vector points, x and y co-ordinate chaff matrixes are generated. New chaff points can be made, by picking best locations from the feature vectors. The optimal locations are found out by using particle swarm optimization (PSO) algorithm. In PSO, extracted feature locations are considered particles and from these locations, best location for generating the chaff feature point is selected based on the fitness value. The experimentation of the proposed work is done on Yale face and IIT Delhi ear databases and its performance are evaluated using the measures such as Jaccard coefficient (JC), Genuine Acceptance Rate (GAR), False Matching Rate (FMR), Dice Coefficient (DC) and False Non Matching Rate (FNMR). The results of the implementation give better recognition of person by facilitating 90% recognition result.

A two-fluid model of Herschel–Bulkley fluid flow through tubes of small diameters and slip at the wall is studied. It is assumed that the core region consists of Herschel–Bulkley fluid and Newtonian fluid in the peripheral region. Following the analysis of Chaturani and Upadhya, the equations of motion have been linearized and analytical solution for velocity, flow flux, effective viscosity, core hematocrit and mean hematocrit has been obtained. The expressions for all these flow relevant quantities have been numerically computed by using Mathematica software and the effects of various relevant parameters on these flow variables have been studied. It is found that effective viscosity, core hematocrit and mean hematocrit of Newtonian fluid are less than those for Bingham fluid, power-law fluid and Herschel–Bulkley fluid. Effective viscosity increases with the yield stress, power-law index, slip and tube hematocrit but decreases with Darcy number. It is observed that the effective viscosity and mean hematocrit increase with tube radius but the core hematocrit decreases with tube radius. Further, it is noticed that the flow exhibits the anomalous Fahraeus–Lindqvist effect.

The detailed surface analysis such as survey scan, core-level, and valence band spectra of highly luminescent ZnO:Na nanocrystals were studied using the x-ray photoelectron spectroscopy to establish the performed presence of Na+ ions. The observed increase in band gap from 3.30 (bulk) to 4.16 eV (nano), is attributed to the quantum confinement of the motion of electron and holes in all three directions. The photoluminescence and decay measurements have complemented and supported our study to design an efficient and ultrafast responsive optical sensing device. [ABSTRACT FROM AUTHOR]

The Distance Education System has taken the shape of a gigantic and intricate system. Gigantic because it has huge number of students, programmes, courses, operations and problems in managing them. It is an intricate system as there are lots of complications in ensuring support to the large number of students. While many things go to its advantage, there are some things, which work as disadvantages. For example, there are a lot of cases of students dropping out midway during their educational sojourn.Most students drop out because of personal circumstances, initial expectations, quality of college facilities or to take up employment, etc. On the other hand, students find that good curriculum design, teaching methods and teacher-student and student-student relationships will have greater impact on dropout rather than the measures that improve facilities. The primary goal of this paper is to study the reasons for student dropout and suggest measures to reduce dropout. This paper applies Cognitive Dissonance Theory and tries to build a model with the help of ICT that can be employed in the Distance Education System (with special reference to IGNOU) to reduce the dropout rates.

Peristaltic transport of two fluid model with micropolar fluid in the core region and Newtonian fluid in the peripheral layer is studied under the assumptions of long wavelength and low Reynolds number. The linearised equations governing the flow are solved and closed form expressions for pressure rise, time averaged flux and frictional force have been obtained. The effects of various parameters on these flow variables have been studied. It is found that the pressure rise increases with micropolar parameter (m) and central mean radius (η), but decreases with coupling number (N) and viscosity ratio (µ¯). The frictional force (F¯) decreases with coupling number (N) and viscosity ratio (µ¯) but increases with micropolar parameter (m) and mean radius of central layer (η).

The motion of a self propelling micro-organism symmetrically located in a rectangular channel containing viscous fluid has been studied by considering the peristaltic and longitudinal waves travelling along the walls of the channel. Theexpressions for the velocity of the micro-organism and time average flux have been obtained under long wavelength approximation by taking into account the viscosity variation of the fluid across the channel. Particular cases for constant viscosity and when it is represented by a step function have been discussed. It has been observed that the velocity of the micro-organism decreases as the viscosity of the peripheral layer increases and its thickness decreases.

Background: The health risks of tobacco use are well known, but kids and teens continue to smoke and use tobacco. Many young people pick up tobacco habits every year; in fact, 90% of all adult smokers began smoking started when they were kids. Aims: The aim of this study was to estimate factors influencing the prevalence of tobacco use among 13–15-year-old high schoolchildren and to assess their knowledge, attitude, and behavior regarding tobacco use. Material and Methods: This pilot study was conducted among 210 schoolchildren selected from three schools based on convenient sampling method. The modified version of Global Youth Tobacco Questionnaire (World Health Organization) was used to measure the knowledge, attitude, and tobacco use of children. The analysis was carried out using the Statistical Package for the Social Sciences software version 17. Descriptive statistics were used for the analysis of the study variables. Chi-square and Fisher's exact tests were applied to test the association of knowledge of and attitude toward factors influencing tobacco use. The level of significance was set at 5%. Results: Of the 210 children participated in the study, 54.8% were boys and 45.2% were girls. Ever tobacco use was reported by 31.4% of children, of which, over 10% reported initiation around 8–10 years of age and 21% of them at 12–15 years of age. Among them, 32 (15.2%) children used the smoking form of tobacco (cigarette, beedi, and other unspecified forms), 27 (12.9%) used the chewing form of tobacco, and 7 (3.3%) participants used both forms. The association was found to be statistically significant with regard to the knowledge (P = 0.03) and attitude scores (P < 0.001). Conclusion: It was found that tobacco use by parents, siblings, and teachers influences the children to initiate tobacco. Knowledge about the harmful effects of tobacco use among children was poor.

Background: This study explores the association of disabilities and oral health. The aim of the study was to assess the salivary and plaque pH and oral health status of children with and without disabilities. Materials and Methods: A total of 100 schoolchildren (50 with disabilities and 50 without disabilities) were examined from 9 to 15 years age group. Saliva and plaque pH analysis were done to both the groups. Clinical data were collected on periodontal status, dental caries using WHO criteria. pH values of different groups, difference between the means were calculated using independent t-test, and frequency distribution was analyzed using Chi-square test. Statistical significance, P value was set at 0.05. Results: Mean plaque and salivary pH scores were lesser (5.73 and 5.67) in children with intellectual disabilities (IDs) (P< 0.001). Subjects with disabilities had also statistically significant higher CPI scores and decayed, missing, and filled scores than their healthy counterparts (P< 0.001). Conclusion: There is a statistically significant difference in plaque and salivary pH among children with and without ID with lower plaque and salivary pH among children with ID. In addition to this, the oral health was also more compromised in children with ID, which confirms a need for preventive treatment for these children.

Introduction: Dental caries is one of the most prevalent diseases affecting children invariably across the world; a toothache is one of the common outcomes found to be associated with dental caries as pain perception is a subjective phenomenon reporting of pain may vary among different individuals. The aim of this study was to assess the difference in oral health status and pain perception related to oral health status among the children with intellectual disability (ID) and their normal counterparts. Materials and Methods: A cross-sectional study was conducted among 100 school children of 9-14 years with or without ID in Bangalore City, ethical clearance and informed consent were obtained. The study involved 50 children with ID and 50 children with non-ID (NID), of age group 9-14 years. A self-administered questionnaire was used to assess participant′s demographic profile, self-assessed medical and dental conditions. Clinical assessment was done for recording dental caries and gingival status. Dental pain was measured using the "Dental Discomfort Questionnaire +" given by Versloot et al. Results: It was found that children with ID had a higher score for D(T), and M(T) compared to NID control. This difference was statistically significant. Children with ID showed higher discomfort due to pain. Except for chewing on one side all other questions showed a significant difference between the groups. Conclusion: It was found that children with ID had a higher caries experience compared to NID control and showed significantly higher pain experience than children with NID.

Introduction: Sugared beverages such as cola, packaged juice, are known for cariogenicity their intake leads to the immediate drop in plaque and salivary pH, which can be an etiologic factor for dental caries. Objective: The objective was to assess the endogenous acidity and total sugar content of four commercially available beverages commonly consumed by children in India and its effect on salivary and plaque pH. Materials and Methods: A crossover controlled trial was conducted. 60 randomly selected school children from school at south Bangalore, who were meeting the inclusion criteria, were asked to refrain from oral hygiene practices for 24 h till the sample collection. Children were divided into four groups and for each group test drink was given. Plaque and salivary sample were collected at the time of 2, 5, 10, 20, and 30 min and were sent for pH estimation. 7 days of washout time was given for each cross-over and 3 such cross-over was done during the study and the drinks were interchanged. Results: Sweet lassi was found to be having maximum total sugar content of and Coca-Cola had the lowest pH 5.3. Milk showed least sugar content and highest pH (6.7). Study showed a significant drop in pH after consumption of all the test drinks (P = 0. 05). Carbonated beverage, that is, Coca-Cola Showed the maximum drop of pH, followed by Pulpy orange in both the plaque as well as saliva. Coca-Cola showed the drop of plaque pH below the critical level, 5.44 (0.134). Conclusion: Sweet lassi showed the maximum inherent total sugar content, lowest inherent pH and maximum fall in plaque and salivary pH, was found with Coca-Cola.

Introduction: Aged people living in residential homes have a higher prevalence of depression and stress which cause oral health-related problems, contributing to excessive morbidity, than do those who live in communities. Aim: To find the relationship between senses of coherence (SOC) and quality of life (QoL) using Geriatric Oral Health Assessment Index (GOHAI) among elderly residents of old age homes in Bengaluru city, India. Materials and Methods: A cross-sectional study was conducted among elderly residents of Bengaluru city, India. Data were collected using a validated questionnaire which record demographic details, oral hygiene practices, and oral health habits. SOC and oral health-related QoL was measured using 13-item short version of the SOC scale and 12-item GOHAI scale. Chi-square test and Pearson's correlation coefficient test were used for statistical analysis. All variables showing significant association (P < 0.05) were entered into a regression model to identify predictors of low GOHAI and SOC. Results: A total of 376 elderly residents participated in the study and completed the questionnaire. Among them 150 (39.9%) were men and 226 (60.1%) were women. SOC was statistically significant with gender (P = 0.008), marital status (P = 0.003), dentition status (P = 0.000), smoking (P = 0.043), and alcohol consumption (P = 0.043). Age (P = 0.036), gender (P = 0.045), dentition status (P < 0.019), and smoking (P = 0.042) were found to be associated with GOHAI, there also exist a strong Pearson's correlation (r = 0.712) between SOC and GOHAI scores. Conclusions: A strong positive correlation was found between SOC and GOHAI scores indicating elder's with low SOC had low GOHAI scores and vice versa. The elders in residential homes were found to have more self-reported oral health-related functional problems, so dental health education must be focused on the special needs of the disabled, dependant and socio – economically deprived geriatric population to improve their QoL.

Introduction: Dental students are the future leaders in oral health care and are expected to be teachers of oral hygiene as well as role models of self-care regimens for their patients. Objective: The objective was to assess self-reported oral health attitude and behavior among undergraduate dental students and to analyze variations between gender and level of education. Materials and Methods: A self-administered questionnaire based on the Hiroshima University-Dental Behavioural Inventory (HU-DBI) was distributed among 270 undergraduate students which consisted of 20 dichotomous responses (yes-no). Data were analyzed using the analysis of variance and statistical significance was set at P < 0.05. Results: Females had better oral health attitude and behavior toward visiting the dentist and oral hygiene practices, mean HU-DBI score of 8.8 (P < 0.05). Furthermore, the preclinical students (1 st , 2 nd years) had better oral health attitude and behavior especially towards gingival health, oral hygiene practices and visiting the dentist (P < 0.05). Conclusion: Among dental students, the overall attitude of oral health was good, even though there were deficits in a few areas. The oral health attitudes and behavior were better among female′s dental students and were not improved with increasing levels of education. Better comprehensive dental education with exposure to dental health and prevention is suggested to improve dental students′ oral health attitudes and behavior.

Introduction: The purpose of this cross-sectional study was to assess and compare self-perceived and normative dental needs among teaching faculty of Visveswarapura Group of Institutions, Bangalore, India. Materials and Methods: The study population included 217 teaching faculty from four Visveswarapura Group of Institutions namely Arts and Commerce, Law, Science College and Engineering College. The study population was subjected to a self-administered closed-ended questionnaire inquiring about their socioeconomic status, Oral health status and treatment needs. Clinical examinations, employing WHO dentition status and community periodontal index were performed to determine normative status and needs. Perceived and normative assessments were compared for sensitivity, specificity, positive and negative predictive values using Kappa statistics. Results: The degree of agreement (κ values) and sensitivity was seen in filled teeth (0.839, 80%), missing teeth (0.696, 85.2%), and mobile teeth (0.57, 55.6%). However, the disagreement was seen with all other questions with average κ = 0.20. Regarding overall proportions, a large discrepancy was found between self-perceived and normative needs for both dental and periodontal health status. Conclusion: Self-assessment questionnaires were of low value in evaluating oral health status and treatment needs compared with clinical examination.

Hydroxyapatite (HAP) is a well-known medically renowned bioactive material known for its excellent biocompatibility and mechanical stability, but it lacks fast bioactivity. The restricted release of ions from hydroxyapatite encourages the search for a faster bioactive material that could replicate other properties of HAP. A new sol-gel-mediated potentially bioactive glass material that could mimic the structure of HAP but can surpass the performance of HAP bioactively has been formulated in this study. Lefebvre et al. suggested that the silicorhenanite phase with the formula Na 2 Ca 4 (PO 4 ) 2 SiO 4 is isostructural to hydroxyapatite; however, data in support of this hypothesis are scant. This study succeeds in developing fast apatite-growth-inducing bioactive glass particles similar to the structure of hydroxyapatite. Also, for the first time, the existence and evolution of two forms of silicorhenanite (α- and β-Na 2 Ca 4 (PO 4 ) 2 SiO 4 ) have been unraveled, and their properties have been explored. The effect of calcination temperature on the phase formation of the biomaterial is notified by looking into the result that heat treatment to 900 °C resulted in α-Na 2 Ca 4 (PO 4 ) 2 SiO 4 (Sili 900) and 1000 °C yielded β-Na 2 Ca 4 (PO 4 ) 2 SiO 4 (Sili 1000). This study conveys a new finding that the hydroxyapatite is isostructural to β-Na 2 Ca 4 (PO 4 ) 2 SiO 4 but not to α-Na 2 Ca 4 (PO 4 ) 2 SiO 4 . Raman spectroscopic analysis proved this structural similarity of Sili 1000 and c-HAP, with relative spectra possessing phosphate bands and the irrelevance of Sili 900 to Sili 1000 and c-HAP. The in vitro MTT assay using NIH 3T3 fibroblasts and in vivo wound healing study confirm the enhanced bioactivity and compatibility of Sili 900 and Sili 1000 compared to c-HAP, favored by the presence of a silica matrix and semicrystallinity. pH analysis proved the rapid ionic leaching out from Sili 900 and Sili 1000 and the faster reactivity of Sili 1000 with the fluid. This rapid burst of ions enhances the clotting ability of the Sili 1000 bioactive material and can be a good ibuprofen drug carrier, which is a potential challenger to hydroxyapatite.

We report the identification of an interesting mode of action by sorafenib (SF) (Nexavar) in triple-negative breast adenocarcinoma MDA-MB-231 cells. The dying cells presented features of apoptosis, such as externalization of phosphatidylserine and cleaved caspase-3, and autophagy-mediated cell death, such as formation of autophagosomes and autolysosomes, the overexpression of LC3-II, and the presence of LAMP1-positive vacuoles, while displaying insufficient autophagic flux. Components of endoplasmic reticulum stress (ER stress; PERK and CHOP) and of necroptosis (p-MLKL) were also elevated considerably. Investigating potential target proteins that could modulate this form of cell death, we next investigated the role of tubulin disruption, which is known to induce necroptosis, apoptosis, and autophagy-dependent cell death. Interactions of SF with purified tubulin were investigated in detail using a combination of cellular and biophysical assays, transmission electron microscopy, and computer simulations. A marked reduction in the intrinsic tryptophan fluorescence of tubulin, a concentration-dependent elevation of anilinonaphthalene sulfonate-tubulin complex fluorescence, electron micrographs of deformed in vitro-assembled microtubules, and disrupted and hyper-stabilized cellular microtubules evinced the ability of SF to target tubulin and disrupt cellular microtubules. Molecular docking and molecular dynamic simulations positioned the drug between the α and β subunits of tubulin with considerable stability (ΔG bind, -31.43 kcal/mol), suggesting that drug-induced perturbation of tubulin could contribute to this mode of cell death., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Collective functionalization of the phytochemicals of medicinal herbs on nanoparticles is emerging as a potential cancer therapeutic strategy. This study presents the facile synthesis of surface-functionalized gold nanoparticles using Bacopa monnieri (Brahmi; Bm ) phytochemicals and their therapeutically relevant mechanism of action in the colorectal cancer cell line, HT29. The nanoparticles were characterized using UV-visible spectroscopy, TEM-EDAX, zeta potential analysis, TGA, FTIR and 1 H NMR spectroscopy, and HR-LC-MS. The particles (Bm-GNPs) were of polygonal shape and were stable against aggregation. They entered the target cells and inhibited the viability and clonogenicity of the cells with eight times more antiproliferative efficacy (25 ± 1.5 μg mL -1 ) than Bm extract (Bm-EX). In vitro studies revealed that Bm-GNPs bind tubulin (a protein crucial in cell division and a target of anticancer drugs) and disrupt its helical structure without grossly altering its tertiary conformation. Like other antitubulin agents, Bm-GNPs induced G 2 /M arrest and ultimately killed the cells, as confirmed using flow cytometry analyses. ZVAD-FMK-mediated global pan-caspase inhibition and the apparent absence of cleaved caspase-3 in treated cells indicated that the death did not involve the classic apoptosis pathway. Cellular ultrastructure analyses, western immunoblots, and in situ immunofluorescence visualization of cellular microtubules revealed microtubule-acetylation-independent induction of autophagy as the facilitator of cell death. Together, the data indicate strong antiproliferative efficacy and a possible mechanism of action for these designer nanoparticles. Bm-GNPs, therefore, merit further investigations, including preclinical evaluations, for their therapeutic potential as inducers of non-apoptotic cell death.

Erastin (ERN) is a small molecule that induces different forms of cell death. For example, it has been reported to induce ferroptosis by disrupting tubulin subunits that maintain the voltage-dependent anion channels (VDACs) of mitochondria. Although its possible binding to tubulin has been suggested, the fine details of the interaction between ERN and tubulin are poorly understood. Using a combination of biochemical, cell-model and in silico approaches, we elucidate the interactions of ERN with tubulin and their biological manifestations. After confirming ERN's antiproliferative efficacy (IC 50 , 20 ± 3.2 M) and induction of cell death in the breast cancer cell line MDA-MB-231, the binding interactions of ERN with tubulin were examined. ERN bound to tubulin in a concentration-dependent manner, disorganizing the structural integrity of the protein, as substantiated via the tryptophan-quenching assay and the aniline-naphthalene sulfonate binding assay, respectively. In silico studies based on molecular docking revealed a docking score of -5.863 kcal/mol, suggesting strong binding interactions of ERN with tubulin. Additionally, molecular dynamics simulation and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analyses evinced the binding free energy (ΔG binding ) of -31.235 kcal/mol, substantiating strong binding affinity of ERN with tubulin. Ligplot analysis showed hydrogen bonding with specific amino acids (Asn A226, Thr A223, Gln B247 and Val B355). QikProp-based ADME (absorption, distribution, metabolism and excretion) assessment showed considerable therapeutic potential for ERN.Communicated by Ramaswamy H. Sarma.

Nanostructured inorganic biomaterial emerged as the most essential platform to address traumatic and non-traumatic conditions of hard tissues in the current scenario. Synthetic inorganic biomaterials serve as an efficient and pathogen-free choice that overcomes the obstructions associated with autografts and allografts to promote new tissue regeneration, since nano-hydroxyapatite (nHAp) is a biomaterial that mimics the natural mineral composition of bones and teeth of human hard tissues, which is widely employed in orthopedics and dentistry. The nHAp-based materials exhibit bioactive, biocompatible, and osteoconductive features under in vitro and in vivo conditions. The brittle nature of synthetic nHAp leads to weak mechanical properties, which eventually confines the utility of nHAp in load-bearing applications. Hence, this review focuses on the recent trends in the fabrication and investigation of nHAp-based polymer nanocomposite scaffolds for bone regeneration. Employing different polymers and fabrication strategies would efficiently tailor the physicochemical properties, and tailor-made mechanical properties in competence with biodegradation, thereby enhancing their potential in biomedical utility, and exploring their efficacy under in vitro and in vivo conditions to make "HAp-based smart-biomaterials" for bone tissue engineering., Competing Interests: Conflicts of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Coronavirus disease 2019 (COVID-19) affects different organ systems, including the skin. There are reports on cutaneous manifestations of COVID-19 available in the literature. In this study, we have tried to describe the dermatological signs of COVID-19 in different categories of patients., Materials and Methods: A descriptive cross sectional study was conducted to describe various cutaneous manifestations of COVID-19 in different categories of reverse transcriptase polymerase chain reaction (RT-PCR)-positive COVID-19 patients in a COVID-designated tertiary care hospital. Approval was obtained from the Institutional Ethical Committee, and 5460 RT-PCR-confirmed COVID-19-positive patients were included under five categories. Investigators following a strict COVID protocol examined and documented the findings. Investigations and treatment were carried out as per the protocol, and the study was conducted for a period of 6 months., Results: Out of the 5460 patients studied, 1.9% patients had cutaneous manifestations. Vasculitis (24%) and maculo papular rash (19%) were the common findings. The incidence of vasculitis was 44.4%, 61%, and 6.6% in categories A, B, and C, respectively. Maculopapular rash and urticaria were the common findings in categories D and E, respectively. COVID digit was seen in only one case. Other manifestations such as acne, adverse drug reaction, erythroderma, and bullous disorders were also noted., Conclusion: Cutaneous manifestations because of vascular pathology were the most common association in severe COVID-19, which indicates that the presence of vasculitic skin signs correlated with disease severity and elevated d-dimer values. Urticaria and maculo-papular rash were transient and did not give any clue to the diagnosis or severity of the disease., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Dermatology Online Journal.)

Chromosomal translocations are considered as one of the major causes of lymphoid cancers. RAG complex, which is responsible for V(D)J recombination, can also cleave non-B DNA structures and cryptic RSSs in the genome leading to chromosomal translocations. The mechanism and factors regulating the illegitimate function of RAGs resulting in oncogenesis are largely unknown. Upon in silico analysis of 3760 chromosomal translocations from lymphoid cancer patients, we find that 93% of the translocation breakpoints possess adjacent cryptic nonamers (RAG binding sequences), of which 77% had CpGs in proximity. As a proof of principle, we show that RAGs can efficiently bind to cryptic nonamers present at multiple fragile regions and cleave at adjacent mismatches generated to mimic the deamination of CpGs. ChIP studies reveal that RAGs can indeed recognize these fragile sites on a chromatin context inside the cell. Finally, we show that AID, the cytidine deaminase, plays a significant role during the generation of mismatches at CpGs and reconstitute the process of RAG-dependent generation of DNA breaks both in vitro and inside the cells. Thus, we propose a novel mechanism for generation of chromosomal translocation, where RAGs bind to the cryptic nonamer sequences and direct cleavage at adjacent mismatch generated due to deamination of meCpGs or cytosines., Competing Interests: The authors have declared that no competing interests exist.

Shikonin (SK), a naphthoquinone compound from the purple gromwell, Lithospermum erythrorhizon, possesses a considerable antiproliferative potential. By using a combination of biophysical techniques, cellular assays, immunofluorescence imaging, and molecular dynamic simulation, we identified a possible mechanism of action of SK. SK inhibited the viability of the triple negative breast cancer cells MDA-MB-231 (IC 50 of 1 ± 0.1 μM), and its inhibitory effect was irreversible. It strongly suppressed the clonogenic and migratory potential of the cells. Although SK did not show any phase-specific inhibition of cell cycle progression, it induced apoptosis as confirmed by annexin-V-based flow cytometry and Western immunoblotting of PARP1. Probing further into its mechanism using a tryptophan-quenching assay, it was found that SK binds the microtubule-building protein tubulin with a dissociation constant (K d ) of 8 ± 2.7 μM, without grossly damaging the tertiary structure of the protein. The drug-bound tubulin could not assemble microtubules properly in vitro as confirmed by polymer mass analysis, turbidimetry analysis, and transmission electron microscopy, and in cells, as visualized by immunofluorescence imaging. In cells, SK also suppressed the dynamicity of microtubules as indicated by considerable acetylation of the cellular microtubules. The fine details of tubulin-SK interactions were then elucidated using molecular docking and molecular dynamic simulation. The free energy change of the interaction (ΔG bind , pred ) was found to be -14.60 kcal/mol and the binding involved both the intermolecular van der Waals (ΔE vdw ) and the electrostatic (ΔE ele ) interactions. Taken together, our data provide evidence for a possible mechanism of action of SK as a tubulin-targeted anticancer agent., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A Zr-based metal organic framework with naphthalene diimide teracarboxylate linkers is reported for its dual electrochromic and photochromic behavior. MOF crystals display reversible yellow to green photochromism upon exposure to visible light and colourless to dark-brown reversible electrochromism on applying a potential of 0 to -2.5 V. The MOF thin film shows good colouration efficiency at 550 nm, which is the highest sensitivity of the human eye.

Many diseases heal spontaneously. The common cold, for example, remedies itself within a few days in people with an uncompromised immune system. If a disease with a poor prognosis heals in the absence of a targeted therapeutic, many even call it a miracle cure. Such is the case with the spontaneous regression (SR) of malignant neoplasms, a rare but well-documented phenomenon that finds its first mention in the Ebers Papyrus of 1550 BCE. Given the challenges associated with current cancer treatment modalities such as rapidly evolving drug resistance mechanisms, dose-limiting side effects, and a failure to completely eliminate cancer cells, knowledge of how a tumour heals itself would be immensely helpful in developing more effective therapeutic modalities. Although the intricate mechanisms of SR have yet to be fully elucidated, it has been shown that infection-mediated immune system activation, biopsy procedures, and disruptions of the tumour microenvironment play pivotal roles in the self-healing of many tumours. Bacterial and viral infections are especially well-documented in instances of SR. Insights from these findings are paving the way for novel therapeutic strategies. Inspired by bacteria-mediated SR, Bacillus Calmette-Guérin (BCG) has been used as an approved treatment option for non-muscle-invasive bladder cancer (NMIBC). Similarly, Talimogene laherparepvec (T-VEC), the first engineered oncolytic herpes simplex virus (HSV), has been approved by the United States Food and Drug Administration for the treatment of some forms of advanced melanoma. Here we describe the current understanding of SR, explore its therapeutic significance, and offer perspectives on its future., (Copyright © 2021. Published by Elsevier Inc.)

Recombination activating genes (RAGs), consisting of RAG1 and RAG2, are stringently regulated lymphoid-specific genes, which initiate V(D)J recombination in developing lymphocytes. We report the regulation of RAG1 through a microRNA (miRNA), miR-29c, in a B cell stage-specific manner in mice and humans. Various lines of experimentation, including CRISPR-Cas9 genome editing, demonstrate the target specificity and direct interaction of miR-29c to RAG1. Modulation of miR-29c levels leads to change in V(D)J recombination efficiency in pre-B cells. The miR-29c expression is inversely proportional to RAG1 in a B cell developmental stage-specific manner, and miR-29c null mice exhibit a reduction in mature B cells. A negative correlation of miR-29c and RAG1 levels is also observed in leukemia patients, suggesting the potential use of miR-29c as a biomarker and a therapeutic target. Thus, our results reveal the role of miRNA in the regulation of RAG1 and its relevance in cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Efficient DNA repair is indispensable for maintaining genomic integrity in humans. Cancer associated deletions and mutations are mainly due to misrepaired DNA double-strand breaks (DSBs). Classical nonhomologous end joining (c-NHEJ) and homologous recombination (HR) are two major DSB repair pathways in humans. An error prone, alternative NHEJ pathway that utilizes microhomology was also reported in cancer cells and to a lesser extent in normal cells. In the present study, we evaluated the efficiency of various DSB repair pathways in the most common lymphoma, the diffuse large B cell lymphoma (DLBCL). Here we show that DNA repair through c-NHEJ pathway is limited in SUDHL8, a cell line derived from a DLBCL patient. Unlike c-NHEJ, microhomology mediated end joining (MMEJ) was predominant at physiological temperature. Consistent with the observation, expression level of repair proteins such as LIGASE I, LIGASE III, PARP1, CtIP, and MRE11 was higher in DLBCL cells when compared to c-NHEJ proteins. Further, inhibition of LIGASE I or MRE11, led to reduction in the efficiency of MMEJ in DLBCL cells. Besides, HR-mediated DSB repair occurring through gene conversion was observed. Thus, our results reveal the predominance of MMEJ over c-NHEJ in repairing DSBs in DLBCL cells, while error-free repair through HR was also evident., (© 2018 Wiley Periodicals, Inc.)

Nonhomologous DNA end joining (NHEJ) is the major DNA double-strand break (DSB) repair pathway in mammals. Previously, we have described a small molecule inhibitor, SCR7, which can inhibit NHEJ in a Ligase IV-dependent manner. Administration of SCR7 within the cells resulted in the accumulation of DNA breaks, cell death, and inhibition of tumor growth in mice. In the present study, we report that parental SCR7, which is unstable, can be autocyclized into a stable form. Both parental SCR7 and cyclized SCR7 possess the same molecular weight (334.09) and molecular formula (C 18 H 14 N 4 OS), whereas its oxidized form, SCR7-pyrazine, possesses a different molecular formula (C 18 H 12 N 4 OS), molecular weight (332.07), and structure. While cyclized form of SCR7 showed robust inhibition of NHEJ in vitro, both forms exhibited efficient cytotoxicity. Cyclized and oxidized forms of SCR7 inhibited DNA end joining catalyzed by Ligase IV, whereas their impact was minimal on Ligase III, Ligase I, and T4 DNA Ligase-mediated joining. Importantly, both forms inhibited V(D)J recombination, although the effect was more pronounced for SCR7-cyclized. Both forms blocked NHEJ in a Ligase IV-dependent manner leading to the accumulation of DSBs within the cells. Although cytotoxicity due to SCR7-cyclized was Ligase IV specific, the pyrazine form exhibited nonspecific cytotoxicity at higher concentrations in Ligase IV-null cells. Finally, we demonstrate that both forms can potentiate the effect of radiation. Thus, we report that cyclized and oxidized forms of SCR7 can inhibit NHEJ in a Ligase IV-dependent manner, although SCR7-pyrazine is less specific to Ligase IV inside the cell., (© 2018 Federation of European Biochemical Societies.)

A remarkable characteristic of majority of cancer cells is that, they fail to undergo apoptosis, which in turn confers them a survival advantage over normal cells. Targeted cancer therapy aims at disrupting the functions of proteins that play an important role during cancer progression. Antiapoptotic protein, BCL2, is one such protein that is highly upregulated in many cancers as compared to normal cells, making it an ideal target for cancer therapy. Although, several BCL2 targeting agents have been investigated over the past 30 years, very few have exhibited any clinical significance. This mini-review outlines a road map of existing BCL2 inhibitors and their relevance in treating cancer, and discusses potential strategies for future research with respect to BCL2 specific cancer therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Among the various oral ailments which have been observed in elderly, root caries is a significant one. Tooth loss is chief oral health-related negative variable to the quality of life in elderly and root caries is the major cause of tooth loss in them. It has been reported about a third of older population bears most of the root caries burden, so the present study aimed to assess the prevalence of root caries among older individuals residing in residential homes of Bengaluru city India., Material and Methods: Elderly individuals aged 60 and above, residing in residential homes of Bangalore city, were included in the study. The study participants filled a questionnaire regarding their demographic details and oral health habits. Root surface caries was recorded according to criteria described by Banting et al. and root caries was expressed in terms of the root caries index (RCI). The statistical analysis was performed using descriptive statistics and chi-square test. P < 0.05 was considered as statistically significant., Results: The prevalence of root caries was 46.4%. The root caries index was 15%. Statistically significant differences (P < 0.05) observed across gender, marital status, diet, socio-economic status, medication, method of cleaning and frequency of cleaning and were identified as significant predictors of root caries., Conclusions: The prevalence of root caries among institutionalized older people was high. Oral health policies and preventive measures are needed focusing on the special needs of this neglected and socioeconomically deprived population to improve their quality of life., Key Words: Elders, residential home, root caries.

This study reports the microwave-assisted synthesis and characterization of nHAp (nano-hydroxyapatite)-alumina composites. The crystalline phase and interaction of alumina with nHAp was analyzed using X-ray diffraction (XRD) and Raman microscopy analysis, respectively. High resolution transmission electron microscopy (HRTEM) micrographs exhibit morphological changes of nHAp composites with increasing alumina concentrations. Microhardness studies reveal the enhanced mechanical strength of nHAp10 and nHAp20 nanocomposites than pure nHAp. In vitro bioactivity of the nanocomposites was studied by immersing samples in simulated body fluid (Hank's solution) for 21 days. The surface of biomineralized samples were analyzed using field emission scanning electron microscopy (FESEM) and energy dispersive X-ray spectroscopy (EDX). Hemolytic assay revealed acceptable compatibility for varying concentrations of all the samples. Cell proliferation assay was systematically investigated for 1 day and 3 days on Saos-2 osteoblast-like cell lines and it was found that nHAp nanocomposites improved the proliferation., (Copyright © 2015 Elsevier B.V. All rights reserved.)