Identification of chemoresistance associated key genes-miRNAs-TFs in docetaxel resistant breast cancer by bioinformatics analysis.

The present study aimed to identify the differentially expressed genes (DEGs) and enriched pathways in docetaxel (DTX) resistant breast cancer cell lines by bioinformatics analysis. The microarray dataset GSE28784 was obtained from gene expression omnibus (GEO) database. The differentially expressed genes (DEGs), gene ontology (GO), and Kyoto Encyclopedia of gene and genome (KEGG) pathway analyses were performed with the help of GEO2R and DAVID tools. Furthermore, the protein-protein interaction (PPI) and hub-gene network of DEGs were constructed using STRING and Cytohubba tools. The prognostic values of hub genes were calculated with the help of the Kaplan-Meier plotter database. From the GEO2R analysis, 222 DEGs were identified of which 120 are upregulated and 102 are downregulated genes. In the PPIs network, five up-regulated genes including CCL2, SPARC, CYR61, F3, and MFGE8 were identified as hub genes. It was observed that low expression of six hub genes CXCL8, CYR61, F3, ICAM1, PLAT, and THBD were significantly correlated with poor overall survival of BC patients in survival analysis. miRNA analysis identified that hsa-mir-16-5p, hsa-mir-335-5p, hsa-mir-124-3p, hsa-mir-20a-5p, and hsa-mir-155-5p are the top 5 interactive miRNAs that are commonly interacting with more hub genes with degree score of greater than five. Additionally, drug-gene interaction analysis was performed to identify drugs which are could potentially elevate/lower the expression levels of hub genes. In summary, the gene-miRNAs-TFs network and subsequent correlation of candidate drugs with hub genes may improve individualized diagnosis and help select appropriate combination therapy for DTX-resistant BC in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03971-2.

Design, Synthesis, and Biological Evaluation of Ferulic Acid Template-Based Novel Multifunctional Ligands Targeting NLRP3 Inflammasome for the Management of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia, which arises due to low levels of acetyl and butyrylcholines, an increase in oxidative stress, inflammation, metal dyshomeostasis, Aß and tau aggregations. The currently available drugs for AD treatment can provide only symptomatic relief without interfering with pathological hallmarks of the disease. In our ongoing efforts to develop naturally inspired novel multifunctional molecules for AD, systematic SAR studies on EJMC-4e were caried out to improve its multifunctional properties. The rigorous medicinal efforts led to the development of 12o, which displayed a 15-fold enhancement in antioxidant properties and a 2-fold increase in the activity against AChE and BChE over EJMC-4e. Molecular docking and dynamics studies revealed the binding sites and stability of the complex of 12o with AChE and BChE. The PAMPA-BBB assay clearly demonstrated that 12o can easily cross the blood-brain barrier. Interestingly, 12o also expresses promising metal chelation activity, while EJMC-4e was found to be devoid of this property. Further, 12o inhibited metal-induced or self Aß1-42 aggregation. Observing the neuroprotection ability of 12o against H2O2-induced oxidative stress in the PC-12 cell line is noteworthy. Furthermore, 12o also inhibited NLRP3 inflammasome activation and attenuated mitochondrial-induced ROS and MMP damage caused by LPS and ATP in HMC-3 cells. In addition, 12o is able to effectively reduce mitochondrial and cellular oxidative stress in the AD Drosophila model. Finally, 12o could reverse memory impairment in the scopolamine-induced AD mice model, as evident through in vivo and ex vivo studies. These findings suggest that this compound may act as a promising candidate for further improvement in the management of AD.

Swallowing dysfunction between the community-living older adults with and without comorbid conditions using Patient-Reported Outcome Measures (PROM).

OBJECTIVE: The present study aimed to investigate older adults' perspective on their swallowing physiology using a PROM tool. The study further explored the swallowing issues among older adults with and without comorbid conditions. METHOD: One hundred twenty-two (122) participants participated in the e-survey. A questionnaire was developed to assess the swallowing deficits among older adults, and Eating Assessment Tool-10 (EAT-10) was administered to assess the PROM. RESULTS: The results revealed that 40% of older adults with comorbid conditions had EAT-10 scores greater than 3, suggesting swallowing deficits. A significant difference was observed between the two groups with respect to swallowing deficits, as reported on EAT-10. CONCLUSION: Based on the results, it can be delineated that swallowing deficits emerge with aging. More of older adults with comorbid conditions reported swallowing deficits in comparison to those without comorbid conditions. Hence, their nutritional and health status gets compromised, leading to poor quality of life.

Scaffold hopping for designing of potent and selective CYP1B1 inhibitors to overcome docetaxel resistance: synthesis and evaluation.

Cytochrome P450 1B1, a tumor-specific overexpressed enzyme, significantly impairs the pharmacokinetics of several commonly used anticancer drugs including docetaxel, paclitaxel and cisplatin, leading to the problem of resistance to these drugs. Currently, there is no CYP1B1 inhibition-based adjuvant therapy available to treat this resistance problem. Hence, in the current study, exhaustive in-silico studies including scaffold hopping followed by molecular docking, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular dynamics and free energy perturbation studies were carried out to identify potent and selective CYP1B1 inhibitors. Initially, scaffold hopping analysis was performed against a well-reported potent and selective CYP1B1 inhibitor (i.e. compound 3n). A total of 200 scaffolds were identified along with their shape and field similarity scores. The top three scaffolds were further selected on the basis of these scores and their synthesis feasibility to design some potent and selective CYP1B1 inhibitors using the aforementioned in-silico techniques. Designed molecules were further synthesized to evaluate their CYP1B1 inhibitory activity and docetaxel resistance reversal potential against CYP1B1 overexpressed drug resistance MCF-7 cell line. In-vitro results indicated that compounds 2a, 2c and 2d manifested IC50 values for CYP1B1 ranging from 0.075, 0.092 to 0.088 µM with at least 10-fold selectivity. At low micromolar concentrations, compounds 1e, 1f, 2a and 2d exhibited promising cytotoxic effects in the docetaxel-resistant CYP1B1 overexpressed MCF-7 cell line. In particular, compound 2a is most effective in reversing the resistance with IC50 of 29.0 ± 3.6 µM. All of these discoveries could pave the way for the development of adjuvant therapy capable of overcoming CYP1B1-mediated resistance.Communicated by Ramaswamy H. Sarma.

Patient Experiences and Insights on Chronic Ocular Pain: Social Media Listening Study.

BACKGROUND: Ocular pain has multifactorial etiologies that affect activities of daily life, psychological well-being, and health-related quality of life (QoL). Chronic ocular surface pain (COSP) is a persistent eye pain symptom lasting for a period longer than 3 months. OBJECTIVE: The objective of this social media listening study was to better understand COSP and related symptoms and identify its perceived causes, comorbidities, and impact on QoL from social media posts. METHODS: A search from February 2020 to February 2021 was performed on social media platforms (Twitter, Facebook, blogs, and forums) for English-language content posted on the web. Social media platforms that did not provide public access to information or posts were excluded. Social media posts from Australia, Canada, the United Kingdom, and the United States were retrieved using the Social Studio platform-a web-based aggregator tool. RESULTS: Of the 25,590 posts identified initially, 464 posts about COSP were considered relevant; the majority of conversations (98.3%, n=456) were posted by adults (aged >18 years). Work status was mentioned in 52 conversations. Patients' or caregivers' discussions across social media platforms were centered around the symptoms (61.9%, n=287) and causes (58%, n=269) of ocular pain. Patients mentioned having symptoms associated with COSP, including headache or head pressure, dry or gritty eyes, light sensitivity, etc. Patients posted that their COSP impacts day-to-day activities such as reading, driving, sleeping, and their social, mental, and functional well-being. CONCLUSIONS: Insights from this study reported patients' experiences, concerns, and the adverse impact on overall QoL. COSP imposes a significant burden on patients, which spans multiple aspects of daily life.

Scaffold hopping based designing of selective ALDH1A1 inhibitors to overcome cyclophosphamide resistance: synthesis and biological evaluation.

Aldehyde dehydrogenase 1A1 (ALDH1A1) is an isoenzyme that catalyzes the conversion of aldehydes to acids. However, the overexpression of ALDH1A1 in a variety of malignancies is the major cause of resistance to an anti-cancer drug, cyclophosphamide (CP). CP is a prodrug that is initially converted into 4-hydroxycyclophosphamide and its tautomer aldophosphamide, in the liver. These compounds permeate into the cell and are converted as active metabolites, i.e., phosphoramide mustard (PM), through spontaneous beta-elimination. On the other hand, the conversion of CP to PM is diverted at the level of aldophosphamide by converting it into inactive carboxyphosphamide using ALDH1A1, which ultimately leads to high drug inactivation and CP resistance. Hence, in combination with our earlier work on the target of resistance, i.e., ALDH1A1, we hereby report selective ALDH1A1 inhibitors. Herein, we selected a lead molecule from our previous virtual screening and implemented scaffold hopping analysis to identify a novel scaffold that can act as an ALDH1A1 inhibitor. This results in the identification of various novel scaffolds. Among these, on the basis of synthetic feasibility, the benzimidazole scaffold was selected for the design of novel ALDH1A1 inhibitors, followed by machine learning-assisted structure-based virtual screening. Finally, the five best compounds were selected and synthesized. All synthesized compounds were evaluated using in vitro enzymatic assay against ALDH1A1, ALDH2, and ALDH3A1. The results disclosed that three molecules A1, A2, and A3 showed significant selective ALDH1A1 inhibitory potential with an IC50 value of 0.32 µM, 0.55 µM, and 1.63 µM, respectively, and none of the compounds exhibits potency towards the other two ALDH isoforms i.e. ALDH2 and ALDH3A1. Besides, the potent compounds (A1, A2, and A3) have been tested for in vitro cell line assay in combination with mafosfamide (analogue of CP) on two cell lines i.e. A549 and MIA-PaCa-2. All three compounds show significant potency to reverse mafosfamide resistance by inhibiting ALDH1A1 against these cell lines.

Studies on a new antimicrobial peptide from Vibrio proteolyticus MT110.

The marine environment is known for its vast diversity of the microbial population; however, less explored for bioactive compounds. In this study, an AMP produced by a new marine isolate, Vibrio proteolyticus MT110, showed broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria. The AMP was purified to homogeneity using ethyl acetate extraction followed by RP-HPLC, and LC-MS analysis showed its molecular weight as 980 Da. The MIC of AMP (peptide-MT110) was obtained in the 7.81-31.25 µg/mL range against different indicator strains. Peptide-MT110 showed stability of its antimicrobial activity at 15-121 °C and pH 4-10 and in the presence of various hydrolytic enzymes. The peaks at 1536 cm-1 and 1712 cm-1 wavenumbers in FTIR spectra confirmed the peptidic nature of AMP, and its amino acid analysis confirmed the presence of tyrosine and isoleucine. The antibacterial activity of peptide-MT110 is confirmed by PI assay and TEM. The optimization of peptide-MT110 production using statistical methods resulted in a 2.64-fold higher production. The physicochemical properties and stability in wide pH and temperature ranges showed the potential of peptide-MT110 for its development as a drug candidate. This is believed to be the first report on an AMP from Vibrio proteolyticus.

Auditory Deficits in Employees of Business Process Outsourcing (BPO): Need to Take Preventative Action.

The present study aimed to explore auditory deficits in full-time call center workers. A total of sixty participants participated, which was divided into two groups, viz. experimental group and control group. The complete audiological test battery was performed. On comparing the groups, significant differences were obtained for both ears while analyzing the TEOAEs, PTA1, and PTA2 (high-frequency audiometry). From the results, it can be delineated that BPO employees are at risk for sensorineural hearing loss following continuous noise exposure. We conclude that this type of hearing loss may be considered an iceberg, and to overcome all the issues related to noise exposure, all BPO employees should undergo periodic audiological, psychological, and health screening.

Audiological, Phonatory and Cardiac Correlates of Individuals Exposed to Low-Frequency Noise or at Risk of Vibroacoustic Disease

Abstract Introduction Low-frequency noise (LFN) is hazardous to hearing. Long-term exposure to LFN may lead to vibroacoustic disease (VAD), which not only affects a specific organ but the physiological function of entire systems, such as the auditory, phonatory, respiratory, and cardiac systems. Moreover, VAD may lead to many psychological problems and hence affect the quality of life. Objective To investigate the adverse effects of LFN on hearing, acoustic and perceptual correlates of the voice, blood pressure, cardiac rate, and anxiety level. Method A total of 20 subjects exposed to LFN and 20 not exposed to LFN were included, and a detailed case history was recorded. The patients were submitted to pure tone audiometry, otoscopic examination, acoustic and perceptual analyses of the voice, maximum phonation time, and an assessment of the s/z ratio. We also assessed blood pressure, and the results of a voice-related quality of life questionnaire and of the Hamilton anxiety rating scale. Results The results indicate that LFN had an adverse impact on the high-frequency threshold. The present study found a significant difference in shimmer and harmonics-to-noise ratio (HNR) values. Few subjects had high blood pressure and showed the sign of anxiety on the Hamilton anxiety rating scale. Conclusion Low-frequency noise has adverse effects on entire systems of the body and causes many psychological issues, which, in turn negatively affect quality of life.

Audiological, Phonatory and Cardiac Correlates of Individuals Exposed to Low-Frequency Noise or at Risk of Vibroacoustic Disease.

Introduction Low-frequency noise (LFN) is hazardous to hearing. Long-term exposure to LFN may lead to vibroacoustic disease (VAD), which not only affects a specific organ but the physiological function of entire systems, such as the auditory, phonatory, respiratory, and cardiac systems. Moreover, VAD may lead to many psychological problems and hence affect the quality of life. Objective To investigate the adverse effects of LFN on hearing, acoustic and perceptual correlates of the voice, blood pressure, cardiac rate, and anxiety level. Method A total of 20 subjects exposed to LFN and 20 not exposed to LFN were included, and a detailed case history was recorded. The patients were submitted to pure tone audiometry, otoscopic examination, acoustic and perceptual analyses of the voice, maximum phonation time, and an assessment of the s/z ratio. We also assessed blood pressure, and the results of a voice-related quality of life questionnaire and of the Hamilton anxiety rating scale. Results The results indicate that LFN had an adverse impact on the high-frequency threshold. The present study found a significant difference in shimmer and harmonics-to-noise ratio (HNR) values. Few subjects had high blood pressure and showed the sign of anxiety on the Hamilton anxiety rating scale. Conclusion Low-frequency noise has adverse effects on entire systems of the body and causes many psychological issues, which, in turn negatively affect quality of life.

Gold Nanorod-Induced Effects in a Mesogenic Compound 4-(trans-4-n-Hexylcyclohexyl) isothiocyanatobenzene.

Gold nanorods (GNRs) have a capsule-like structure with different optical properties than spherical gold nanoparticles due to surface plasmon resonance. Liquid crystals (LCs) are mesogenic compounds having crystal-like orientation and liquid-like fluidity. They are important materials from a technological point of view. Both GNRs and LC compounds are anisotropic in shape and properties. Different nano entities show interesting results when dispersed in different liquid crystalline materials which are instrumental from the application point of view. In the present work, GNRs have been dispersed in nematic liquid crystalline materials, namely 4-(trans-4-n-hexylcyclohexyl) isothiocyanatobenzene (6CHBT). Calorimetric, texture, spectroscopic, and dielectric studies were carried out for a pure 6CHBT and its composites with GNRs. Different calorimetric and dielectric parameters such as transition temperature, enthalpy, heat flow, permittivity, dielectric strength, dielectric anisotropy, and relaxation frequency have been determined, and the effect of GNRs has been explored. This article gives an insight into the influence of GNRs on the morphology and anisotropic physical properties of the nematic liquid crystalline material.

Evaluation of Cordyceps militaris steroids as anti-inflammatory agents to combat the Covid-19 cytokine storm: a bioinformatics and structure-based drug designing approach.

Since the SARS-CoV-2 epidemic, researchers have been working on figuring out ways to tackle multi-organ failure and hyperinflation, which are brought on by a cytokine storm. Angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike glycoprotein's cellular receptor, is involved in complicated molecular processes that result in hyperinflammation. Cordyceps militaris is one of the traditional Chinese medicines that is used as an immune booster, and it has exhibited efficacy in lowering blood glucose levels, seminal emissions, and infertility. In the current study, we explored the potential of Cordyceps militaris steroids as key agents in managing the anger of cytokine storm in Covid-19 using network ethnopharmacological techniques and structure-based drug designing approaches. The steroids present in Cordyceps militaris were initially screened against the targets involved in inflammatory pathways. The results revealed that out of 16 steroids, 5 may be effective against 17 inflammatory pathways by targeting 11 pathological proteins. Among the five steroids, beta-sitosterol, Cholest-5-en-3ß-ol, 3ß, and 7α-Dihydroxycholest-5-ene were found to interact with thrombin (F2), an important protein reported to reduce the severity of inflammatory mediators and Cholest-4-en-3-one was found to target Glucocorticoid receptor (NR3C1). The top docked steroid displayed key interactions with both targets, which retained key interactions throughout the 100 ns simulation period. These compounds were also shown high binding free energy scores in water swap studies. Based on obtained results the current study suggests the use of Cordyceps militaris as an add-on therapy that may reduce the progression of inflammatory co-morbidities among patients infected with SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Transadaptation and Validation of the Telugu Version of the Dysphagia Handicap Index.

Dysphagia Handicap Index (DHI) is a clinically effective, concise, and user-friendly tool for assessing the functional impact of dysphagia in clinical populations. The present study aims to trans-adapt the DHI in the Telugu language and assesses its psychometric properties. The present study was conducted in two phases. The first phase includes translating and adapting the DHI tool into Telugu (T-DHI). The second phase includes an analysis of the psychometric properties of the trans-adapted Telugu version of the DHI. The DHI was translated into the Telugu language using the forward-backward translation method. The psychometric analysis was done on 100 participants. All the participants underwent a detailed clinical swallow examination after filling the T-DHI. The overall internal consistency and Guttmann split-half reliability for the Telugu version of the DHI were good. The correlation between the T-DHI subscales and the self-perceived severity of dysphagia was found to be high. The comparison of the T-DHI scores of the control and experimental groups revealed a significant difference. The T-DHI is a reliable and valid tool to assess the quality of life of the Telugu-speaking dysphagia population.

Raloxifene and bazedoxifene as selective ALDH1A1 inhibitors to ameliorate cyclophosphamide resistance: A drug repurposing approach.

Cyclophosphamide (CP) is one of the most widely used anticancer drugs for various malignancies. However, its long-term use leads to ALDH1A1-mediated inactivation and subsequent resistance which necessitates the development of potential ALDH1A1 inhibitors. Currently, ALDH1A1 inhibitors from different chemical classes have been reported, but these failed to reach the market due to safety and efficacy problems. Developing a new treatment from the ground requires a huge amount of time, effort, and money, therefore it is worthwhile to improve CP efficacy by proposing better adjuvants as ALDH1A1 inhibitors. Herein, the database constituting the FDA-approved drugs with well-established safety and toxicity profiles was screened through already reported machine learning models by our research group. This model is validated for discriminating the ALDH1A1 inhibitors and non-inhibitors. Virtual screening protocol (VS) from this model identified four FDA-approved drugs, raloxifene, bazedoxifene, avanafil, and betrixaban as selective ALDH1A1 inhibitors. The molecular docking, dynamics, and water swap analysis also suggested these drugs to be promising ALDH1A1 inhibitors which were further validated for their CP resistance reversal potential by in-vitro analysis. The in-vitro enzymatic assay results indicated that raloxifene and bazedoxifene selectively inhibited the ALDH1A1 enzyme with IC50 values of 2.35 and 4.41 µM respectively, whereas IC50 values of both the drugs against ALDH2 and ALDH3A1 was >100 µM. Additional in-vitro studies with well-reported ALDH1A1 overexpressing A549 and MIA paCa-2 cell lines suggested that mafosfamide sensitivity was further ameliorated by the combination of both raloxifene and bazedoxifene. Collectively, in-silico and in-vitro studies indicate raloxifene and bazedoxifene act as promising adjuvants with CP that may improve the quality of treatment for cancer patients with minimal toxicities.

Identification of natural peptides from "PlantPepDB" database as anti-SARS-CoV-2 agents: A protein-protein docking approach.

Background: A global pandemic owing to COVID-19 infection has created havoc in the entire world. The etiological agent responsible for this viral outbreak is classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Still, there's no specific drug or preventive medication to treat SARS-CoV-2. This study was designed to demonstrate the efficacy of some anti-viral peptides obtained from a plant database i.e., PlantPepDB as potential ACE-2-Spike (S) protein complex neutralizers using a structure-based drug designing approach. Method: A total of 83 anti-viral plant peptides were screened from a peptide database i.e. PlantPepDB based on their reported anti-viral activities against various viral strains. In order to screen peptides that may potentially interfere with ACE-2 and S complex formation, molecular docking studies were conducted using the flare module of Cresset software and subsequently, analysed the crucial interactions between the peptides and S complexes and ACE-2/S complex. Herein, the interactions and docking scores obtained for ACE-2/S complex were considered as references. The S-peptides complexes which displayed superior interactions and docking scores than reference complex i.e., ACE2-S were considered as final hits. The Molecular dynamics studies were conducted for a period of 30 ns for each of the final hit/S complex to understand the interaction stability and binding mechanism of designed peptides. Results: The molecular docking results revealed that five peptides including Cycloviolacin Y3, Cycloviolacin Y1, White cloud bean defensin, Putative defensin 3.1, and Defensin D1 showed superior docking scores (i.e. -1372.5 kJ/mol to -1232.6 kJ/mol) when docked at the ACE2 binding site of S-protein than score obtained for the complex of ACE-2 and S protein i.e. -1183.4 kJ/mol. Moreover, these top five peptides manifested key interactions required to prevent the binding of S protein with ACE2. The molecular dynamics simulation study revealed that two of these five peptides i.e. Cycloviolacin Y3 and Cycloviolacin Y1 displayed minimal RMSD fluctuations. Conclusions: The current structure-based drug-designing approach shows the possible role of anti-viral plant peptides as potential molecules to be explored at the initial stage of viral pathogenesis.

QuantImage v2: a comprehensive and integrated physician-centered cloud platform for radiomics and machine learning research.

BACKGROUND: Radiomics, the field of image-based computational medical biomarker research, has experienced rapid growth over the past decade due to its potential to revolutionize the development of personalized decision support models. However, despite its research momentum and important advances toward methodological standardization, the translation of radiomics prediction models into clinical practice only progresses slowly. The lack of physicians leading the development of radiomics models and insufficient integration of radiomics tools in the clinical workflow contributes to this slow uptake. METHODS: We propose a physician-centered vision of radiomics research and derive minimal functional requirements for radiomics research software to support this vision. Free-to-access radiomics tools and frameworks were reviewed to identify best practices and reveal the shortcomings of existing software solutions to optimally support physician-driven radiomics research in a clinical environment. RESULTS: Support for user-friendly development and evaluation of radiomics prediction models via machine learning was found to be missing in most tools. QuantImage v2 (QI2) was designed and implemented to address these shortcomings. QI2 relies on well-established existing tools and open-source libraries to realize and concretely demonstrate the potential of a one-stop tool for physician-driven radiomics research. It provides web-based access to cohort management, feature extraction, and visualization and supports "no-code" development and evaluation of machine learning models against patient-specific outcome data. CONCLUSIONS: QI2 fills a gap in the radiomics software landscape by enabling "no-code" radiomics research, including model validation, in a clinical environment. Further information about QI2, a public instance of the system, and its source code is available at https://medgift.github.io/quantimage-v2-info/ . Key points As domain experts, physicians play a key role in the development of radiomics models. Existing software solutions do not support physician-driven research optimally. QuantImage v2 implements a physician-centered vision for radiomics research. QuantImage v2 is a web-based, "no-code" radiomics research platform.

In silico guided designing of optimized benzochalcones derivatives as potent CYP1B1 inhibitors: An integrated in vitro and ONIOM study.

Cytochrome P4501B1 (CYP1B1) is reported to be overexpressed in various malignancies including ovarian, lung, lymph, and breast cancers. The overexpression of this enzyme is accountable for the biotransformation-based inactivation of some anti-cancer drugs i.e. Docetaxel, Paclitaxel, and Cisplatin. To circumvent solutions to this issue, the current study reports some optimized derivatives of benzochalcone as selective CYP1B1 inhibitors. The optimized derivatives were screened using some structure-based drug-designing approaches including molecular docking and molecular dynamics. The implemented approaches revealed that all the designed molecules demonstrated not only essential interactions with key amino acid residues but also maintained stability within the active site of CYP1B1. Furthermore, to validate the in-silico results and develop a SAR, the designed molecules were subsequently synthesized and tested for their ability to selectively inhibit CYP1B1 over CYP1A1 using well established EROD assay. This assay results suggested that compounds 1(c), 1(d), and 1(e) are eightfold more selective CYP1B1 inhibitors over CYP1A1 with IC50 values ranging from 0.06 to 0.09 µM respectively. Among these, compound 1(d) manifested potent inhibitory activity i.e. IC50 of 0.06 µM with 24 folds selectivity over 1A1. To have a better insight into the binding pattern of 1(d) within CYP1B1 and precisely compute binding affinity for 1(d)-CYP1B1 complex, one of the advanced QM/MM approaches i.e. ONIOM has been implemented. Where 1(d)-CYP1B1 complex conferred comparable binding affinity in terms of ΔG (kcal/mol) with that of ANF-CYP1B1 complex. This research could provide a suitable starting point for the development of more potent multi-functional compounds with CYP1B1 inhibitory activity.

Trans-Adaptation and Analysis of Psychometric Properties of Hindi Version of Eating Assessment Tool-10 (EAT-10H).

The present study aims to trans-adapt the Eating Assessment Tool-10 (EAT-10) to the Hindi language and assess its psychometric properties. The original EAT-10 was translated into Hindi language using the forward-backward translation method. A total of 201 participants were included in the study. Among 201 participants, 83 were controls, and 118 were dysphagic. Internal consistency, reliability, and clinical validity were measured. Results revealed that the Hindi version of EAT-10 exhibited an excellent internal consistency (i.e., 0.86). A significant difference was found between the mean scores of both groups, and an excellent reliability score (i.e., 0.96) was obtained. From the present study's findings, it can be delineated that the Hindi version of EAT-10 exhibited good psychometric properties. So, the developed tool is a quick, reliable, and valid tool.