Evaluation of Child Preference for Dentist Attire and Usage of a Camouflage Syringe in Reduction of Anxiety.

Objective: This study aimed to evaluate the effect of child-friendly dentist attire and camouflage syringes on reducing dental anxiety in children. Methods: A cross-sectional study was conducted with 120 pediatric patients aged 6 to 12 years. Participants were assigned to one of three groups: group A (child-friendly dentist attire), group B (camouflage syringe), or group C (control group). Child preference for dentist attire was assessed using a visual analog scale, while dental anxiety was measured using the Modified Child Dental Anxiety Scale and the Facial Image Scale. Results: The results showed a significant decrease in dental anxiety scores in both group 2 and group 3 compared to group 1 (P < 0.001). Children in group A exhibited a higher preference for child-friendly dentist attire [mean score: 8.7, standard deviation (SD): 1.2] compared to group 1 (mean score: 3.2, SD: 1.5) (P < 0.001). Similarly, children in group 2 showed a higher preference for a camouflage syringe (mean score: 8.5, SD: 1.3) compared to group 1 (mean score: 3.4, SD: 1.6) (P < 0.001). Conclusion: Child-friendly dentist attire and camouflage syringes were found to be effective in reducing dental anxiety among pediatric patients. These interventions were well received by children and their parents, highlighting the importance of considering child preferences in dental settings.

Water-Soluble Small Organic Fluorophores for Oncological Theragnostic Applications: Progress and Development.

Cancer is one of the major noncommunicable diseases, responsible for millions of deaths every year worldwide. Though various cancer detection and treatment modalities are available today, many deaths occur owing to its late-stage detection and metastatic nature. Noninvasive detection using luminescence-based imaging tools is considered one of the promising techniques owing to its low cost, high sensitivity, and brightness. Moreover, these tools are unique and valuable as they can detect even the slightest changes in the cellular microenvironment. To achieve this, a fluorescent probe with strong tumor uptake and high spatial and temporal resolution, especially with high water solubility, is highly demanded. Recently, several water-soluble molecules with emission windows in the visible (400-700 nm), first near-infrared (NIR-I, 700-1000 nm), and second near-infrared (NIR-II, 1000-1700 nm) windows have been reported in literature. This review highlights recently reported water-soluble small organic fluorophores/dyes with applications in cancer diagnosis and therapeutics. We systematically highlight and describe the key concepts, structural classes of fluorophores, strategies for imparting water solubility, and applications in cancer therapy and diagnosis, i.e., theragnostics. We discuss examples of water-soluble fluorescent probes based on coumarin, xanthene, boron-dipyrromethene (BODIPY), and cyanine cores. Some other emerging classes of dyes based on carbocyclic and heterocyclic cores are also discussed. Besides, emerging molecular engineering methods to obtain such fluorophores are discussed. Finally, the opportunities and challenges in this research area are also delineated.

Synthesis, Characterization, Antiglycation Evaluation, Molecular Docking, and ADMET Studies of 4-Thiazolidinone Derivatives.

The design and development of new small-molecule glycation inhibitors are essential for preventing various chronic diseases, including diabetes mellitus, immunoinflammation, cardiovascular, and neurodegenerative diseases. 4-Thiazolidinone or thiazolidine-4-one is a well-known heterocyclic compound with the potential to inhibit the formation of advanced glycation end products. In the present work, we report the synthesis and characterization of four new 5-arylidene 3-cyclopropyl-2-(phenylimino)thiazolidin-4-one (1-4) compounds and their human serum albumin glycation inhibitory activity. One of the compounds 5-(2H-1,3-benzodioxol-5-ylmethylidene)-3-cyclopropyl-2-(phenylimino)-1,3-thiazolidin-4-one (3) showed potent inhibition in the synthesis of initial, intermediary, and final products of glycation reactions. Besides, conformational changes in the α-helix and ß-sheet (due to hyperglycemia) were also found to be reversed upon the addition of (3). Experimental findings were complemented by computational [molecular docking, ADME/Tox, and density functional theory (DFT)] studies. The docking scores of the compounds were in order 1 > 3 > 2 > 4, indicating the importance of the polar group at the 5-arylidene moiety. The results of ADME/Tox and DFT calculations revealed the safe nature of the compounds with high drug-likeness and stability. Overall, we speculate that the results of this study could provide valuable insights into the biological activity of 4-thiazolidinones.

Synthesis, Characterization, Cytotoxicity, Cellular Imaging, Molecular Docking, and ADMET Studies of Piperazine-Linked 1,8-Naphthalimide-Arylsulfonyl Derivatives.

To reduce the mortality and morbidity associated with cancer, new cancer theranostics are in high demand and are an emerging area of research. To achieve this goal, we report the synthesis and characterization of piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives (SA1-SA7). These compounds were synthesized in good yields following a two-step protocol and characterized using multiple analytical techniques. In vitro cytotoxicity and fluorescent cellular imaging of the compounds were assessed against non-cancerous fibroblast (3T3) and breast cancer (4T1) cell lines. Although the former study indicated the safe nature of the compounds (viability = 82-95% at 1 µg/mL), imaging studies revealed that the designed probes had good membrane permeability and could disperse in the whole cell cytoplasm. In silico studies, including molecular docking, molecular dynamics (MD) simulation, and ADME/Tox results, indicated that the compounds had the ability to target CAIX-expressing cancers. These findings suggest that piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives are potential candidates for cancer theranostics and a valuable backbone for future research.

Synthesis, anticancer activity, molecular docking and molecular dynamics studies of some pyrazole-chalcone hybrids.

Four new hybrid compounds (H1-H4) bearing pyrazole (S1 and S2) and chalcone (P1 and P2) fragments were synthesized and characterized. Compounds were assayed for their ability to inhibit the proliferation of human lung (A549) and colon (Caco-2) cancer cell lines. Besides, toxicity against normal cells was determined using the human umbilical vein endothelial cells (HUVEC). In silico molecular docking, molecular dynamics (MD) simulation and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were carried out to predict the binding modes, protein stability, drug-likeness and toxicity of the reported compounds. The in vitro anticancer activity of the tested compounds revealed dose-dependent cell-specific cytotoxicity. In silico studies revealed that the compounds have a good binding affinity, possess appropriate drug-likeness properties and have low toxicity profiles.Communicated by Ramaswamy H. Sarma.

Knowledge and Barriers About Blood Donation and Associated Factors in Saudi Arabia: A Systematic Review.

Transfusions and blood donations are relatively risk-free medical procedures. However, attitudes, beliefs, and knowledge levels about blood donation and transfusion may influence such operations. This systematic review aims to comprehensively investigate the level of knowledge and attitudes towards blood donation in Saudi Arabia. PubMed, Scopus, Web of Science, and ScienceDirect were systematically searched for relevant literature. Rayyan (Qatar Computing Research Institute, Ar-Rayyan, Qatar) was employed throughout this comprehensive process. This review included 17 studies with a total of 9,212 patients, and 4,806 (52.2%) were males. The majority of Saudis lacked awareness about blood donation and had unfavorable opinions towards it. In addition to various fears, mistrust, a lack of information, and not being approached by anyone to donate blood, participants reported that the distance to the donation site, the difficulty with transportation, the time commitment, getting a quick break from work or the office, or taking time off from home were also contributing to the negative attitudes towards blood donation. While youthful participants were more likely to contribute, Saudi university students in this study had inadequate information but positive attitudes about blood donation. Ineligibility, fear of giving blood, and inaccurate information regarding blood donation are the main deterrents to blood donation.

In silico evaluation of 4-thiazolidinone-based inhibitors against the receptor for advanced glycation end products (RAGE).

Non-enzymatic glycation of biomolecules by reducing sugars led to several products, including the advanced glycation end products (AGEs), the accumulation of which has been linked to various life-threatening diseases. The binding of AGEs to their respective protein receptors for advanced glycation end products (RAGE) can initiate a cascade of reactions, which may alter physiological conditions. The present work investigates the potential of 4-thiazolidinones as RAGE inhibitors. We performed an extensive computational study to identify the structural requirements needed to act as RAGE inhibitors. To achieve this goal, 4-thiazolidinone-based compounds available in PubChem, ZINC15, ChEMBL, and ChEBI databases were screened against RAGE (PDB: 4LP5), leading to the identification of top five drug-like candidates with a high binding affinity to RAGE V-domain catalytic region. Drug likeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the top-scoring compounds have been studied and discussed. Global molecular descriptors, chemical reactivity, hardness, softness, etc., have been estimated. Finally, molecular dynamics (MD) simulations at 100 ns were carried out to check the stability and other properties. Overall, we believe that the identified compounds can potentially attenuate RAGE-AGE interactions.Communicated by Ramaswamy H. Sarma.

Fractional modeling of drug diffusion from cylindrical tablets based on Fickian and relaxed approaches with in vivo validation.

Mathematical simulation of drug diffusion is a significant tool for predicting the bio-transport process. Moreover, the reported models in the literature are based on Fick's approach, which leads to an infinite propagation speed. Consequently, it is essential to construct a mathematical model to represent the diffusion processes for estimating drug concentrations at different sites and throughout the circulation. Thus, in this article, the diffusion process is employed to propose three models for estimating the drug release from multi-layer cylindrical tablets. A fractional model is presented based on Fick's approach, while classical and fractional Cattaneo models are presented using the relaxed principle. Various numerical methods are used to solve the specified problem. The numerical scheme's stability and convergence are demonstrated. Drug concentration and mass profiles are presented for the tablet and the external medium and compared with the in vivo plasma profiles. The results show the efficiency and precision of the proposed fractional models based on the fourth-order weighted-shifted Grünwald-Letnikov difference operator approximation. These models are compatible with the in vivo data compared with the classical Fick's one.

Titanium dioxide nanoparticles require K+ and hydrogen sulfide to regulate nitrogen and carbohydrate metabolism during adaptive response to drought and nickel stress in cucumber.

Crop plants face severe yield losses worldwide owing to their exposure to multiple abiotic stresses. The study described here, was conducted to comprehend the response of cucumber seedlings to drought (induced by 15% w/v polyethylene glycol 8000; PEG) and nickel (Ni) stress in presence or absence of titanium dioxide nanoparticle (nTiO2). In addition, it was also investigated how nitrogen (N) and carbohydrate metabolism, as well as the defense system, are affected by endogenous potassium (K+) and hydrogen sulfide (H2S). Cucumber seedlings were subjected to Ni stress and drought, which led to oxidative stress and triggered the defense system. Under the stress, N and carbohydrate metabolism were differentially affected. Supplementation of the stressed seedlings with nTiO2 (15 mg L-1) enhanced the activity of antioxidant enzymes, ascorbate-glutathione (AsA-GSH) system and elevated N and carbohydrates metabolism. Application of nTiO2 also enhanced the accumulation of phytochelatins and activity of the enzymes of glyoxalase system that provided additional protection against the metal and toxic methylglyoxal. Osmotic stress brought on by PEG and Ni, was countered by the increase of proline and carbohydrates levels, which helped the seedlings keep their optimal level of hydration. Application nTiO2 improved the biosynthesis of H2S and K+ retention through regulating Cys biosynthesis and H+-ATPase activity, respectively. Observed outcomes lead to the conclusion that nTiO2 maintains redox homeostasis, and normal functioning of N and carbohydrates metabolism that resulted in the protection of cucumber seedlings against drought and Ni stress. Use of 20 mM tetraethylammonium chloride (K+- channel blocker), 500 µM sodium orthovanadate (PM H+-ATPase inhibitor), and 1 mM hypotaurine (H2S scavenger) demonstrate that endogenous K+ and H2S were crucial for the nTiO2-induced modulation of plants' adaptive responses to the imposed stress.

New Epoxy and Hardener System Based on an Imidazolium Ionic Liquid as an Anticorrosive Coating for Steel in the Marine Environment.

The large sizes of cations and anions of organic salts are the driving force for the application of ionic liquids (organic salts) in harsh salty conditions. Moreover, the formation of crosslinked ionic liquid networks as anti-rust and anticorrosion protective films on the substrate surfaces repels seawater salt and water vapor from their surface to prevent corrosion. In this respect, an imidazolium epoxy resin and polyamine hardener as ionic liquids were prepared by the condensation of either pentaethylenehexamine or ethanolamine with glyoxal and p-hydroxybenzaldehyde or formalin in acetic acid as a catalyst. The hydroxyl and phenol groups of the imidazolium ionic liquid were reacted with epichlorohydrine in the presence of NaOH as a catalyst to prepare polyfunctional epoxy resins. The chemical structure, nitrogen content, amine value, epoxy equivalent weight, thermal characteristics, and stability of the imidazolium epoxy resin and polyamine hardener were evaluated. Moreover, their curing and thermomechanical properties were investigated to confirm the formation of homogeneous, elastic, and thermally stable cured epoxy networks. The corrosion inhibition and salt spray resistance of the uncured and cured imidazolium epoxy resin and polyamine as coatings for steel in seawater were evaluated.

Intranasal antihistamines in the treatment of idiopathic non-allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: Idiopathic rhinitis (IR), previously known as vasomotor rhinitis (VMR), is the most common type of non-allergic rhinitis (NAR) which affects around 100 million people worldwide. The treatment of patients with IR is not standardized. Intranasal antihistamines (INAH) are potent drugs in the treatment of allergic rhinitis but are frequently prescribed in the treatment of IR. This systematic review of the literature and meta-analysis aims to assess the effects of INAH on IR. METHODOLOGY: A comprehensive review of the literature was conducted on Medline, Embase and Cochrane library. Randomized, controlled trials and non-randomized comparative parallel group trials comparing INAH to placebo or different INAHs were included. The primary outcome was the change in disease specific quality of life questionnaires, total nasal symptom score (TNSS). The secondary outcomes were other reported nasal symptom scores, individual symptom scores and adverse events. RESULTS: Six trials out of 987 assessing a total of 675 participants were deemed relevant for inclusion. Compared to placebo, INAH decreased total nasal symptom scores. One study also reported reduction of symptoms recorded on a visual analogue scale. There was no difference between the INAHs in terms of efficacy. Bitter taste sensation was the most frequently reported adverse event. CONCLUSIONS: INAHs seem to have benefit over placebo on nasal symptoms improvement in the treatment of NAR. No superiority between INAHs was identified.

Chemical, biological and in silico assessment of date (P. dactylifera L.) fruits grown in Ha'il region.

Background: Dates palm (Phoenix dactylifera L.) fruits are among the most widely used fruits in the Middle East and African nations. Numerous researchers confirmed the presence of phytochemicals in P. dactylifera L. fruit and its by-products with broad-ranging biological activities. Objectives: In the present work, phytochemical and biological assessments of two different cultivars of date fruit (Shishi M1 and Majdool M2 grown in the Ha'il region of Saudi Arabia) have been carried out. Methods: Date fruits were extracted and analyzed by gas chromatography-mass spectrometry (GS-MS),liquid chromatography-mass spectrometry (LC-MS) and Fourier-transform infrared spectroscopy (FT-IR)techniques. The lyophilized methanolic extracts were analyzed for their in-vitro antiproliferative andcytotoxicity against colon cancer (HCT116) cell line. To identify the possible constituents responsible for the bioactivity, in-silico molecular docking and molecular dynamics (MD) simulation studies were carried out. Results: Both cultivars exhibited in-vitro anticancer activity (IC50 = 591.3 µg/mL and 449.9 µg/mL for M1 and M2, respectively) against colon cancer HCT-116 cells. The computational analysis results indicated procyanidin B2 and luteolin-7-O-rutinoside as the active constituents. Conclusion: Based on these results, we conclude that these cultivars could be a valuable source for developing health promoter phytochemicals, leading to the development of the Ha'il region, Saudi Arabia.

Melatonin involves hydrogen sulfide in the regulation of H+-ATPase activity, nitrogen metabolism, and ascorbate-glutathione system under chromium toxicity.

Contamination of soils with chromium (Cr) jeopardized agriculture production globally. The current study was planned with the aim to better comprehend how melatonin (Mel) and hydrogen sulfide (H2S) regulate antioxidant defense system, potassium (K) homeostasis, and nitrogen (N) metabolism in tomato seedlings under Cr toxicity. The data reveal that application of 30 µM Mel to the seedlings treated with 25 µM Cr has a positive effect on H2S metabolism that resulted in a considerable increase in H2S. Exogenous Mel improved phytochelatins content and H+-ATPase activity with an associated increase in K content as well. Use of tetraethylammonium chloride (K+-channel blocker) and sodium orthovanadate (H+-ATPase inhibitor) showed that Mel maintained K homeostasis through regulating H+-ATPase activity under Cr toxicity. Supplementation of the stressed seedlings with Mel substantially scavenged excess reactive oxygen species (ROS) that maintained ROS homeostasis. Reduced electrolyte leakage and lipid peroxidation were additional signs of Mel's ROS scavenging effects. In addition, Mel also maintained normal functioning of nitrogen (N) metabolism and ascorbate-glutathione (AsA-GSH) system. Improved level of N fulfilled its requirement for various enzymes that have induced resilience during Cr stress. Additionally, the AsA-GSH cycle's proper operation maintained redox equilibrium, which is necessary for the biological system to function normally. Conversely, 1 mM hypotaurine (H2S scavenger) abolished the Mel-effect and again Cr-induced impairment on the above-mentioned parameters was observed even in presence of Mel. Therefore, based on the observed findings, we concluded that Mel needs endogenous H2S to alleviate Cr-induced impairments in tomato seedlings.

Non-covalent interactions (NCIs) in π-conjugated functional materials: advances and perspectives.

The design and development of functional materials with real-life applications are highly demanding. Understanding and controlling inter- and intra-molecular interactions provide opportunities to design new materials. A judicious manipulation of the molecular structure significantly alters such interactions and can boost selected properties and functions of the material. There is burgeoning evidence of the beneficial effects of non-covalent interactions (NCIs), showing that manipulating NCIs may generate functional materials with a wide variety of physical properties leading to applications in catalysis, drug delivery, crystal engineering, etc. This prompted us to review the implications of NCIs on the molecular packing, optical properties, and applications of functional π-conjugated materials. To this end, this tutorial review will cover different types of interactions (electrostatic, π-interactions, metallophilic, etc.) and their impact on π-conjugated materials. Attempts have also been made to delineate the effects of weak interactions on opto-electronic (O-E) applications.

Characterization and application of ligno-cellulosic fibers derived from Robinia Pseudoacacia for the bio-sorption of methylene blue from water.

Ligno-cellulosic biomasses had been recognized for their potential use to produce chemicals and biomaterials. The current study focused on the use of a new cellulosic Robinia Pseudoacacia fiber and extracted lignin as adsorbents for methylene blue (a cationic dye). The biomaterials were analyzed using FT-IR spectroscopy, SEM, XRD, and TGA-DTA techniques. The surface of Robinia fibers was rough and porous. The crystallinity index (CrI) value for Robinia fibers was found to be 32%. The ability of the studied samples to remove methylene blue from water was assessed under the variation of time, pH, dye concentration, temperature, and NaCl concentration. The maximum adsorption capacity of methylene blue reached 191 mg/g for Robinia fibers and it achieved 22 mg/g for the extracted lignin (T = 20 °C, pH = 6, and time = 90 min). The adsorption data complied with the pseudo second-order kinetic model and both Langmuir and Freundlich isotherms. Based on these findings, the process suggested the occurrence of many physicochemical interactions between methylene blue molecules and the studied biomaterials. The adsorption mechanism was exothermic, non-spontaneous, and it was described by the decrease of the disorder. Adsorption results proved that Robinia fiber was an attractive candidate for the removal of cationic dyes from water.

A low-cost and abundant Robinia Pseudoacacia fiber and its extracted lignin are characterized and further studied as adsorbents for cationic dyes under the change of the experimental conditions.

Carvacrol mitigates vancomycin-induced nephrotoxicity via regulation of IkBα/p38MAPK and Keap1/Nrf2 signaling pathways: an experimental study with in silico evidence.

OBJECTIVE: Despite its evident renal toxicity, vancomycin is considered an effective glycopeptide antibiotic against life-threatening positive bacterial contagions. The current study aimed to investigate the potential protective effects of carvacrol as well as its underlying mechanism against vancomycin-induced nephrotoxicity. MATERIALS AND METHODS: The animals were randomly classified into four groups (8 rats per group). Group I, which served as a control group, received only vehicles. Group II received a single i.p. injection of 50 mg/kg of carvacrol for seven days. Group III received vancomycin (200 mg/kg, i.p.) as a singular daily dose for seven days. Carvacrol was administered to Group IV seven days prior to the daily vancomycin dose. RESULTS: The results revealed that carvacrol minimized vancomycin-induced renal injury as evidenced by lower serum cystatin C levels and kidney injury molecule-1 (KIM-1), in addition to a decline in renal damage caused by vancomycin as indicated in histopathological assessment. Furthermore, carvacrol significantly attenuated oxidative stress parameters and inflammatory mediators. Moreover, it downregulated Keap1, mitogen-activated protein kinase (p38MAPK), and nuclear factor kappa B (NF-κB) genes and proteins, along with controlling the NF-κB inhibitory protein (IkBα) and nuclear factor erythroid 2-related factor 2 (Nrf2) genes and proteins observed through streaming its genes. A molecular docking technique was also used to investigate the potential interactivity between carvacrol and proteins involved in regulating oxidative injury and inflammatory responses. CONCLUSIONS: The current study findings revealed that carvacrol administration before vancomycin could be a promising therapeutic approach for maceration of renal damage stimulated by vancomycin via controlling IkBα/MAPK and Keap1/Nrf2 signaling molecules.https://www.europeanreview.org/wp/wp-content/uploads/graphical-abstract-1.jpg.

Synthesis of Mixed Arylalkyl Tertiary Phosphines via the Grignard Approach.

Trialkyl and triaryl phosphines are important classes of ligands in the field of catalysis and materials research. The wide usability of these low-valent phosphines has led to the design and development of new synthesis routes for a variety of phosphines. In the present work, we report the synthesis and characterization of some mixed arylalkyl tertiary phosphines via the Grignard approach. A new asymmetric phosphine is characterized extensively by multi-spectroscopic techniques. IR and UV-Vis spectra of some selected compounds are also compared and discussed. Density functional theory (DFT)-calculated results support the formation of the new compounds.

Synthesis and characterization of a new meso-tetrakis (2,4,6-trimethylphenyl) porphyrinto) zinc(II) supported sodium alginate gel beads for improved adsorption of methylene blue dye.

Chemical modification of a biopolymer offers a simple strategy to realize new materials with added benefits. In this paper, meso-tetrakis(2,4,6-trimethylphenyl) porphyrinto) zinc(II) supported sodium alginate gel beads were successfully prepared, characterized, and used for the removal of a cationic dye from aqueous solution. The chemical structure of the prepared composite beads was confirmed by FT-IR, SEM, XRD and TGA/DTG techniques. Analytical data suggested that the sodium alginate beads and meso-tetrakis(2,4,6-trimethylphenyl) porphyrinto) zinc(II) complex interacted via non-covalent interaction (H-bonding) mode. The morphological micrographs showed spherical and smooth composite beads. The crosslinking of hydroxyl and carboxylate groups of the biopolymer with calcium ions and the incorporation of meso-tetrakis(2,4,6-trimethylphenyl) porphyrinto) zinc(II) into alginate matrix resulted in a small decrease of residual mass. The maximum adsorption capacities of methylene blue, at 20 °C, were found to be 52.3 mg/g and 34.8 mg/g for sodium alginate composite beads (3%) and plain sodium alginate beads, respectively. The adsorption process followed Freundlich isotherm and pseudo second order kinetics. The thermodynamic study displayed an exothermic and non-spontaneous process.

Multiple targets of Nrf 2 inhibitor; trigonelline in combating urethane-induced lung cancer by caspase-executioner apoptosis, cGMP and limitation of cyclin D1 and Bcl2.

OBJECTIVE: Among other types of cancerous lesions, lung cancer is one of the prevalent causes of death. Trigonelline is a plant alkaloid, a significant constituent in coffee, and has shown health benefits in several disorders. The present study aims to investigate the potential therapeutic role of trigonelline in lung cancer. MATERIALS AND METHODS: Seventy-five BALB/C mice were assigned to five groups and treated for 150 days as follows (1): normal control group; (2) trigonelline only (50 mg/kg/ P.O) daily for the last thirty days; (3) urethane (1.5 g/kg B.w/i.p) at day one and sixty; (4) urethane and carboplatin (15 mg/kg i.p) for the last thirty days; and (5) urethane and trigonelline for the last thirty days. Tumor size was measured while blood and lung were collected for biochemical, western blotting analysis, and histological examinations. RESULTS: Urethane demonstrated significant changes in all biochemical and molecular parameters and histological examinations. In animals pretreated with urethane, trigonelline significantly reduced tumor size and restored Nrf2, NF-кB p65, Bcl-2, Cyclin D1, ICAM-1, and MMP-2, along with improving cGMP and active caspase three and refining histological architectures. CONCLUSIONS: Nrf2 signaling may be a promising therapeutic target for adenocarcinoma protection or management. Due to its multiple therapeutic effects on Nrf2, cyclin D1, NF-кB pathways, and the BAX/Bcl2 axis, trigonelline significantly induced cell cycle arrest and apoptosis.https://www.europeanreview.org/wp/wp-content/uploads/Graphical_Abstract-1.jpg.

Synthesis, characterization, anticancer and in silico studies of a pyrazole-tethered thiazolidine-2,4-dione derivative.

A new pyrazole-tethered thiazolidine-2,4-dione derivative (8) has been synthesized by the Knoevenagel condensation of 3-(4-nitrophenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (4) and 3-(2,4-dioxothiazolidin-3-yl)propanenitrile (7). The structure of the final compound was confirmed by standard spectroscopic techniques including IR spectroscopy, 1H-NMR spectroscopy, and ESI-MS mass spectrometry. Molecular features including frontier molecular orbital (HOMO-LUMO) energies, reactivity descriptors and molecular electrostatic potential (ESP) of the title molecule were determined using density functional theory (DFT) calculation. The in vitro cytotoxicity of both the intermediate (4) and final (8) compounds were investigated against cancerous (SW-480 and MCF-7) and normal (HEK-293) cell lines by MTT assay. Compound (8) displayed higher activity than (4) with higher sensitivity against breast cancer cell line and lesser toxicity. The experimental data were further complemented by docking and absorption, distribution, metabolism, and excretion (ADME) studies.Communicated by Ramaswamy H. Sarma.