Design and Development of Halogenated Chalcone Derivatives as Potential Anticancer Agents

Purpose: To design and develop halogenated chalcone derivatives and evaluate them as anticancer agents using different cancer cell lines.Methods: Based on in silico design and docking on known target, crystal structure of the complex of interleukin-1beta converting enzyme (ICE) with a peptide based inhibitor, (3S )-N-Methanesulfonyl-3- ({1-[N-(2-naphtoyl)-l-valyl]-l-prolyl}amino)-4-oxobutanamide (1BMQ), novel halogenated chalcone derivatives were designed (7a-h) employing LigandFit module of Accelrys (Discovery Studio, 2.1 version). Standard protocols for ligand and protein preparation were employed and their binding orientation validated using (3S)-N-Methanesulfonyl-3-({1-[N-(2-naphtoyl)-l-valyl]-l-prolyl}amino)-4-oxobutanamide (MNO 601), a caspase inhibitor as reference standard. Energy minimized conformers with best dock scores were considered for the identification of interacting amino acid residues with ligands. Selected derivatives were synthesized and analyzed by melting point, 1H NMR, IR and mass spectroscopy. Their evaluation for anticancer activity was carried out using adriamycin, paclitaxel and 5-fluorouracil as reference standards on prostrate (PC-3), colon (COLO-205), ovary (OVCAR-5), liver (HEP-2) and neuroblastoma (IMR-32) cancer cell lines, and % growth inhibition and half maximal inhibitory concentration (IC50) values were calculated.Results: Among synthesized compounds, 7b showed the most promising cytotoxic activity with an IC50 of 49.9 ìM on colon cancer cell lines (Colo-205), followed by 7d with an IC50 of 66.6 ìM against ovarian cancer cell lines (OVCAR-5).Conclusion: We report the successful synthesis, spectral characterization and in vitro anticancer evaluation of a series of novel halogenated chalcone derivatives against a number of human cancer cell lines. The findings indicate the emergence of new anticancer compounds.Keywords: Halogenated chalcones, Dock scores, Anticancer activity,  Interleukin-1beta converting enzyme

Ethylene and sulfur coordinately modulate the antioxidant system and ABA accumulation in mustard plants under salt stress

This study explored the interactive effect of ethephon (2-chloroethyl phosphonic acid; an ethylene source) and sulfur (S) in regulating the antioxidant system and ABA content and in maintaining stomatal responses, chloroplast structure, and photosynthetic performance of mustard plants (Brassica juncea L. Czern.) grown under 100 mM NaCl stress. The treatment of ethephon (200 µL L−1) and S (200 mg S kg−1 soil) together markedly improved the activity of enzymatic and non-enzymatic components of the ascorbate-glutathione (AsA-GSH) cycle, resulting in declined oxida-tive stress through lesser content of sodium (Na+) ion and hydrogen peroxide (H2O2) in salt-stressed plants. These changes promoted the development of chloroplast thylakoids and photosynthetic performance under salt stress. Ethephon + S also reduced abscisic acid (ABA) accumulation in guard cell, leading to maximal stomatal conductance under salt stress. The inhibition of ethylene action by norbornadiene (NBD) in salt-plus non-stressed treated plants increased ABA and H2O2 contents, and reduced stomatal opening, suggesting the involvement of ethephon and S in regulating sto-matal conductance. These findings suggest that ethephon and S modulate antioxidant system and ABA accumulation in guard cells, controlling stomatal conductance, and the structure and efficiency of the photosynthetic apparatus in plants under salt stress

Soil sulfur sources differentially enhance cadmium tolerance in indian mustard (Brassica juncea L.)

The effect of four soil-applied sulfur (100 mg S kg−1 soil (100S) and 200 mg S kg−1 soil (200S)) in different sources (elemental S, ammonium sulfate, gypsum or magnesium sulfate) in protecting mustard (Brassica juncea L. (Czern & Coss.)) from cadmium effects was studied. Based on the observed reduction in growth and photosynthesis in plants subjected to 100 and 200 mg Cd kg−1 soil, B. juncea cv. Giriraj was selected as the most Cd-tolerant among five cultivars (namely, Giriraj, RH0749, Pusa Agrani, RH-406, and Pusa Tarak). Sulfur applied to soil mitigated the negative impact of Cd on sulfur assimilation, cell viability, and photosynthetic functions, with a lower lipid peroxidation, electrolyte leakage, and contents of reactive oxygen species (ROS: hydrogen peroxide, H2O2, and superoxide anion, O2•−). Generally, added S caused higher activity of antioxidant enzymes (ascorbate peroxidase, catalase and superoxide dismutase), contents of ascorbate (AsA) and reduced glutathione (GSH); increases in the activities of their regenerating enzymes (dehydroascorbate reductase and glutathione reductase); as well as rises in S assimilation, biosynthesis of non-protein thiols (NPTs), and phytochelatins (PCs). Compared to the other S-sources tested, elemental S more prominently protected B. juncea cv. Giriraj against Cd-impacts by minimizing Cd-accumulation and its root-toshoot translocation; decreasing cellular ROS and membrane damage, and improving Cd-chelation (NPTs and PCs), so strengthening the defense machinery against Cd. The results suggest the use of elemental S for favoring the growth and development of cultivated plants also in Cd-contaminated agricultural soils

Salicylic acid increases photosynthesis of drought grown mustard plants effectively with sufficient-N via regulation of ethylene, abscisic acid, and nitrogen-use efficiency

An essential approach to reduce drought in plants is to maximize the use of most limited available resources. The increase in water-use efficiency (WUE) is important to maximally utilize the available water to increase photosynthesis and growth of plants under water-deficit stress. Both WUE and photosynthetic nitrogen-use efficiency (PNUE), as the indices of resource-use efficiency were studied in mustard (Brassica juncea L.) plants grown under limited water conditions with low-N (100 mg N kg−1 soil) and sufficient-N (200 mg N kg−1 soil) and sprayed with 0 or 0.5 mM salicylic acid (SA). Application of SA increased water potential, osmotic potential, WUE, and the incorporation of soil N into photosynthetic machinery by enhancing PNUE. It also increased photosynthesis of plants maximally by increasing stomatal conductance and intercellular CO2 concentration under water-deficit stress. This increase was greater in the presence of sufficient-N where 0.5 mM SA maximally enhanced the N metabolism, redox ratio that mitigated the oxidative stress. The application of SA on plants supplemented with N reduced ethylene and abscisic acid (ABA) synthesis. It could be inferred that SA enhanced N utilization through increase in NUE when it is sufficiently available, increasing the GSH content to maintain redox ratio and inhibit ABA-mediated stomatal closure to enhance the resource utilization and photosynthesis. SA also enhanced glucose utilization which prevented glucose-mediated photosynthetic repression under stress. Thus, SA application may impart a potential management tool for increasing photosynthetic NUE, WUE, and photosynthesis under drought

Classification of Spherically Symmetric Static Spacetimes according to their Matter Collineations

The spherically symmetric static spacetimes are classified according to their matter collineations. These are studied when the energy-momentum tensor is degenerate and also when it is non-degenerate. We have found a case where the energy-momentum tensor is degenerate but the group of matter collineations is finite. For the non-degenerate case, we obtain either {\it four}, {\it five}, {\it six} or {\it ten} independent matter collineations in which four are isometries and the rest are proper. We conclude that the matter collineations coincide with the Ricci collineations but the constraint equations are different which on solving can provide physically interesting cosmological solutions.Comment: 15 pages, no figure, Late

Phenazine virulence factor binding to extracellular DNA is important for Pseudomonas aeruginosa biofilm formation

Bacterial resistance to conventional antibiotics necessitates the identification of novel leads for infection control. Interference with extracellular phenomena, such as quorum sensing, extracellular DNA integrity and redox active metabolite release, represents a new frontier to control human pathogens such as Pseudomonas aeruginosa and hence reduce mortality. Here we reveal that the extracellular redox active virulence factor pyocyanin produced by P. aeruginosa binds directly to the deoxyribose-phosphate backbone of DNA and intercalates with DNA nitrogenous base pair regions. Binding results in local perturbations of the DNA double helix structure and enhanced electron transfer along the nucleic acid polymer. Pyocyanin binding to DNA also increases DNA solution viscosity. In contrast, antioxidants interacting with DNA and pyocyanin decrease DNA solution viscosity. Biofilms deficient in pyocyanin production and biofilms lacking extracellular DNA show similar architecture indicating the interaction is important in P. aeruginosa biofilm formation

A hybrid dependency-based approach for Urdu sentiment analysis

In the digital age, social media has emerged as a significant platform, generating a vast amount of raw data daily. This data reflects the opinions of individuals from diverse backgrounds, races, cultures, and age groups, spanning a wide range of topics. Businesses can leverage this data to extract valuable insights, improve their services, and effectively reach a broader audience based on users’ expressed opinions on social media platforms. To harness the potential of this extensive and unstructured data, a deep understanding of Natural Language Processing (NLP) is crucial. Existing approaches for sentiment analysis (SA) often rely on word co-occurrence frequencies, which prove inefficient in practical scenarios. Identifying this research gap, this paper presents a framework for concept-level sentiment analysis, aiming to enhance the accuracy of sentiment analysis (SA). A comprehensive Urdu language dataset was constructed by collecting data from YouTube, consisting of various talks and reviews on topics such as movies, politics, and commercial products. The dataset was further enriched by incorporating language rules and Deep Neural Networks (DNN) to optimize polarity detection. For sentiment analysis, the proposed framework employs predefined rules to trigger sentiment flow from words to concepts, leveraging the dependency relations among different words in a sentence based on Urdu language grammatical rules. In cases where predefined patterns are not triggered, the framework seamlessly switches to its sub-symbolic counterpart, passing the data to the DNN for sentence classification. Experimental results demonstrate that the proposed framework surpasses state-of-the-art approaches, including LSTM, CNN, SVM, LR, and MLP, achieving an improvement of 6–7% on Urdu dataset. In conclusion, this research paper introduces a novel framework for concept-level sentiment analysis of Urdu language data sourced from social media platforms. By combining language rules and DNN, the proposed framework demonstrates superior performance compared to existing methodologies, showcasing its effectiveness in accurately analyzing sentiment in Urdu text data

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Not AvailableThe apple and pear have a significant place in the horticulture sector of Jammu & Kashmir. The planted areas have been expanding quiet significantly since 1990s. Advanced technologies for these crops have been rationalized and adopted by the growers; however, seasonal and annual variations of the fruit supplies continue to characterize prices at both wholesale and consumption levels. In this study, Nerlovian model has been used to estimate supply response, Engle- Granger test and Vector Error Correction Model have been used to estimate the long-run and short-run dynamics. The study has revealed that the price of apple has more variation compared to price of pear. The existence of correlation between the prices of apple and pear suggests that there exist both long-run and short-run relationships between the prices of these commodities. The results have exhibited a high value of R2 (95%) and estimated own price elasticities of 0.32 and 0.33 in apple and 0.03 and 0.28 in pear, respectively in short- and long-run. The results have further revealed that the price of pear has a positive and significant impact on price of apple, as demonstrated by their respective coefficients. The study has concluded that if price of apple increases, people can opt for pear which has turned out to be an alternative crop.Not Availabl

Abstract Number ‐ 242: Safety and Effectiveness of Intravenous Thrombolytic in Patients with Concurrent Migraine‐Headaches and Focal Neurological Deficits.

Introduction It is relatively well recognized that migraine headaches can present with focal neurological deficits. Current guidelines do not exclude such patients from receiving intravenous recombinant tissue plasminogen activator (rt‐PA). Methods We reviewed the records of migraine patients with ischemic stroke using a combination of retrospective chart review and prospective identification. The migraine was classified based on the criteria proposed by the third International Classification of Headache Disorders (ICHD‐3) into migraine with aura, and hemiplegic migraine. We ascertained rates of early neurological improvement (defined by reduction in National Institutes of Health Stroke Scale (NIHSS) score of 4 points or greater or NIHSS score of 0 at24 hours), any intracerebral hemorrhage within 24 hours, and excellent functional outcome based on modified Rankin Scale (mRS 0–1) at one month. Results A total of 25 patients (mean age ± SD; 45.3 ± 10.6 years; 15 were women) who met the criteria of migraine headaches concurrently presented with focal neurological deficits and received intravenous rt‐PA. The migraine was classified as hemiplegic migraine and migraine with aura in 22 and 3 patients, respectively. Intravenous rt‐PA was administered at a mean period of 142 minutes(range 60–255 minutes). Computed tomographic angiography was performed in 24 patients and did not reveal any large vessel arterial occlusion. Early neurological improvement was seen in 13 of 25 patients. None of the patients developed post thrombolytic intracerebral hemorrhage. Excellent functional outcome was seen in all patients. Diffusion‐weighted magnetic resonance imaging (MRI) was performed in 25 patients within 72 hours of symptom onset and demonstrated a new infarction in 1 patient. Conclusions In our analysis, intravenous rt‐PA was associated with high rates of early neurological improvement and excellent functional outcome at 1 month in patients with concurrent migraine headaches and focal neurological deficits