Discovery of novel octahydroquinazoline scaffolds endowed with dual inhibition of tubulin polymerization/Eg5 against HCC: Apoptotic and radio-chemotherapeutic studies.

Mitotic kinesin Eg5 isozyme as a motor protein plays a critical role in cell division of tumor cells. Kinesin Eg5 selective inhibitors and Colchicine binding site suppressors are essential targets for many anticancer drugs and radio chemotherapies. On this work, a new series of octahydroquinazoline as anti-mitotic candidates 2-13 has been synthesized with dual inhibition of tubulin polymerization/Eg5 against HCC cell line. All octahydroquinazolines have been in vitro assayed against HepG-2 cytotoxicity, Eg5 inhibitory and anti-tubulin polymerization activities. The most active analogues 7, 8, 9, 10, and 12 against HepG-2 were further subjected to in vitro cytotoxic assay against HCT-116 and MCF-7 cell lines. Chalcones 9, 10, and 12 displayed the most cytotoxic potency and anti-tubulin aggregation in comparable with reference standard colchicine and potential anti-mitotic Eg5 inhibitory activity in comparison with Monastrol as well. Besides, they exhibited cell cycle arrest at the G2/M phase. Moreover, good convinced apoptotic activities have been concluded as overexpression of caspase-3 levels and tumor suppressive gene p53 in parallel with higher induction of Bax and inhibition of Bcl-2 biomarkers. Octahydroquinazoline 10 displayed an increase in caspase-3 by 1.12 folds compared to standard colchicine and induce apoptosis and demonstrated cell cycle arrest in G2/M phase arrest by targeting p53 pathway. Analogue 10 has considerably promoted cytotoxic radiation activity and boosted apoptotic induction in HepG-2 cells by 1.5 fold higher than standard colchicine.

Exploring predictors and prevalence of postpartum depression among mothers: Multinational study.

BACKGROUND: Postpartum depression (PPD) affects around 10% of women, or 1 in 7 women, after giving birth. Undiagnosed PPD was observed among 50% of mothers. PPD has an unfavorable relationship with women's functioning, marital and personal relationships, the quality of the mother-infant connection, and the social, behavioral, and cognitive development of children. We aim to determine the frequency of PPD and explore associated determinants or predictors (demographic, obstetric, infant-related, and psychosocial factors) and coping strategies from June to August 2023 in six countries. METHODS: An analytical cross-sectional study included a total of 674 mothers who visited primary health care centers (PHCs) in Egypt, Yemen, Iraq, India, Ghana, and Syria. They were asked to complete self-administered assessments using the Edinburgh Postnatal Depression Scale (EPDS). The data underwent logistic regression analysis using SPSS-IBM 27 to list potential factors that could predict PPD. RESULTS: The overall frequency of PPD in the total sample was 92(13.6%). It ranged from 2.3% in Syria to 26% in Ghana. Only 42 (6.2%) were diagnosed. Multiple logistic regression analysis revealed there were significant predictors of PPD. These factors included having unhealthy baby adjusted odds ratio (aOR) of 11.685, 95% CI: 1.405-97.139, p = 0.023), having a precious baby (aOR 7.717, 95% CI: 1.822-32.689, p = 0.006), who don't receive support (aOR 9.784, 95% CI: 5.373-17.816, p = 0.001), and those who are suffering from PPD. However, being married and comfortable discussing mental health with family relatives are significant protective factors (aOR = 0.141 (95% CI: 0.04-0.494; p = 0.002) and (aOR = 0.369, 95% CI: 0.146-0.933, p = 0.035), respectively. CONCLUSION: The frequency of PPD among the mothers varied significantly across different countries. PPD has many protective and potential factors. We recommend further research and screenings of PPD for all mothers to promote the well-being of the mothers and create a favorable environment for the newborn and all family members.

Systematic Implications of Palynomorph Diversity Using Microscopic Trends Among Asteraceous Flora From the Drylands of Baluchistan, Pakistan.

Pollen micromorphological traits with taxonomic implications are first reported from the study area for 50 Asteraceous taxa belonging to nine tribes. Cichorieae (21 taxa), Cardueae (11 taxa), Inuleae (six taxa), and Anthemideae (four taxa) are the leading tribes. The research included Cousinia haeckeliae, Himalaiella afghana, Pterachaenia stewartii (endemic to Afghanistan and Pakistan), and Xylanthemum macropodum (endemic to Baluchistan). Light and scanning electron microscopy were employed for the visualization of pollen photomicrographs. The data was analyzed statistically via SPSS, PAST, and Origin. Significant diagnostic qualitative and quantitative palynological traits were explored for discrimination down to the species level within the tribes. All the investigated taxa possessed radial symmetry, isopolarity, and monad form (characters for distinction at the subdivision level). The aperture types were trizonocolporate, tetrazonocolporate, and tricolporate with number position and character (NPC) formulas N3P4C5, N4P4C5, and N3P4C3. Goniotreme, peritreme, and ptychotreme types of amb were recognized. Echinate, echinate lophate, scabrate, and gemmate sculpturing were present with and without perforated surface patterns. Variations in the shapes in polar and equatorial views and lacuna shapes further assisted the separation of taxa. The observed shape classes were perprolate, prolate spheroidal, prolate, subprolate, oblate spheroidal, suboblate, and oblate. Principal component analysis, correlation, standard probability plots, and ridge line paired features plot for quantitative variables determined the positive correlation between the length and width of colpi in equatorial and polar view with polar axis and equatorial diameter and number of spines between colpi with the number of spines per pollen. The number of spines per pollen was negatively correlated with the width and length of colpi in the polar view. Multiple sample analysis of variance (ANOVA) concluded that a high statistically significant difference exists among the means of analyzed traits. The examined qualitative and quantitative palynological traits revealed noticeable variations, thus providing the source for species discrimination in Asteraceous tribes.

Hazardous waste management (Buxus papillosa) investment for the prosperity of environment and circular economy: Response surface methodology-based simulation.

Dealing with the current defaults of environmental toxicity, heating, waste management, and economic crises, exploration of novel non-edible, toxic, and waste feedstock for renewable biodiesel synthesis is the need of the hour. The present study is concerned with Buxus papillosa with seeds oil concentration (45% w/w), a promising biodiesel feedstock encountering environmental defaults and waste management; in addition, this research performed simulation based-response surface methodology (RSM) for Buxus papillosa bio-diesel. Synthesis and application of novel Phyto-nanocatalyst bimetallic oxide with Buxus papillosa fruit capsule aqueous extract was advantageous during transesterification. Characterization of sodium/potassium oxide Phyto-nanocatalyst confirmed 23.5 nm nano-size and enhanced catalytic activity. Other characterizing tools are FTIR, DRS, XRD, Zeta potential, SEM, and EDX. Methyl ester formation was authenticated by FTIR, GC-MS, and NMR. A maximum 97% yield was obtained at optimized conditions i.e., methanol ratio to oil (8:1), catalyst amount (0.37 wt%), reaction duration (180 min), and temperature of 80 °C. The reusability of novel sodium/potassium oxide was checked for six reactions. Buxus papillosa fuel properties were within the international restrictions of fuel. The sulphur content of 0.00090% signified the environmental remedial nature of Buxus papillosa methyl esters and it is a highly recommendable species for biodiesel production at large scale due to a t huge number of seeds production and vast distribution.

Phytochemicals, Health-Promoting Effects, and Enzyme Inhibition Traits of Phlomis stewartii Extracts.

Phlomis stewartii is a wild, perennial woody plant used for diverse therapeutic targets. The present work evaluated the influence of independent variables such as extraction time, solvent concentration, and speed in the range of (100 mL, 150 mL, and 200 mL), (2 h, 5 h, and 8 h), and (100 rpm, 150 rpm, and 200 rpm), respectively, on extraction yields, phytochemical components, total phenolic contents (TPC), and total flavonoid contents (TFC) of P. stewartii extract. In the present work, response surface methodology (RSM) was applied to optimize the extraction yield. High-performance liquid chromatography (HPLC) was performed to detect the bioactive constituents of the extracts. The potent extracts were analyzed to study α-amylase and α-glucosidase inhibitory activities. Under the optimized conditions of solvent concentration (200 mL), extraction time (8 h), and speed (150 rpm), the whole plant methanol extract (WPME) showed a maximum extraction yield of 13.5%, while the leaves methanol extract (LME) showed a maximum TPC of 19.5 ± 44 mg of gallic acid equivalent (GAE) per gram of extract and a maximum TFC of 4.78 ± 0.34 mg of quercetin equivalent (QE) per gram of extract. HPLC analysis showed the presence of p-coumaric, gallic acid, quercetin, salicylic acid, sinapic acid, and vanillic acid. LME showed the highest α-amylase inhibitory activity (IC50 = 46.86 ± 0.21 µg/mL) and α-glucosidase inhibitory activity (IC50 value of 45.81 ± 0.17 µg/mL). Therefore, in conclusion, LME could be considered to fix the α-amylase and α-glucosidase-mediated disorders in the human body to develop herbal phytomedicine.

Clinicopathological significance of protein disulphide isomerase A3 and phosphorylated signal transducer and activator of transcription 3 in cervical carcinoma.

Introduction: Death in cervical cancer patients is usually due to invasion and metastasis due to the aggressive nature of the tumour. Therefore, it is critical to identify potent therapeutic targets and prognostic markers to detect high-risk patients. Material and methods: We assessed the immunohistochemical expression of protein disulphide isomerase A3 (PDIA3) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in 50 cases of cervical carcinoma, and we investigated their association with clinicopathological characteristics. Results: High PDIA3 was detected in 50% of cases, and statistical analysis revealed a positive correlation between high PDAI3 expression and tumour grade (p < 0.001) and large tumour size (p = 0.010), depth of stromal invasion (p = 0.017), lymph-vascular invasion (p = 0.005), parametrial invasion (p < 0.001), nodal metastasis (p < 0.001), and higher International Federation of Gynaecology and Obstetrics stages (p < 0.001). Positive nuclear expression of p-STAT3 was detected in 44% of cases and showed significant association with histological grade (p = 0.036), tumour stage (p = 0.021), nodal metastasis (p = 0.020), and parametrial invasion (p = 0.045); statistical analysis of the patient's survival data revealed that shorter overall survival and disease-free survival, S, were associated with high PDIA3 expression and positive p-STAT3 immunoexpression. Conclusions: The high expression of PDIA3 and p-STAT3 was related to highly aggressive cervical carcinoma with poor prognosis, and high risk of recurrence after the standardised protocol of treatment. Hence, both PDIA3 and p-STAT3 could be considered as novel biomarkers for tumour progression and promising targets in the management of cervical carcinoma patients.

Synthesis and Antiproliferative Potential of Thiazole and 4-Thiazolidinone Containing Motifs as Dual Inhibitors of EGFR and BRAFV600E.

Thiazole and thiazolidinone recur in a wide range of biologically active compounds that reach different targets within the context of tumors and represent a promising starting point to access potential candidates for treating metastatic cancer. Therefore, searching for new lead compounds that show the highest anticancer potency with the fewest adverse effects is a major drug-discovery challenge. Because the thiazole ring is present in dasatinib, which is currently used in anticancer therapy, it is important to highlight the ring. In this study, cycloalkylidenehydrazinecarbothioamides (cyclopentyl, cyclohexyl, cyclooctyl, dihydronapthalenylidene, flurine-9-ylidene, and indolinonyl) reacted with 2-bromoacetophenone and diethylacetylenedicarboxylate to yield thiazole and 4-thiazolidinone derivatives. The structure of the products was confirmed by using infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and single-crystal X-ray analyses. The antiproliferative activity of the newly synthesized compounds was evaluated. The most effective inhibitory compounds were further tested in vitro against both epidermal growth factor receptor (EGFR) and B-Raf proto-oncogene, serine/threonine kinase (BRAFV600E) targets. Additionally, molecular docking analysis examined how these molecules bind to the active sites of EGFR and BRAFV600E.

Mechanism underlying the anti-diabetic potential of bee venom as compared to bone marrow mesenchymal stem cells in the diabetic rat tongue.

BACKGROUND: Diabetes mellitus (DM) is a critical chronic metabolic disease. Several treatment modalities are currently under investigation. Both bee venom (BV) and bone marrow mesenchymal stem cells (BMSCs) can possibly offer an approach for treating type I diabetes. OBJECTIVES: The aim of the present study was to investigate the mechanism underlying the anti-diabetic effect of BV as compared to BMSCs on the tongue mucosa of diabetic rats. MATERIAL AND METHODS: A total of 52 male albino rats were used in the current study. The rats were randomly assigned into 4 groups: group 1 (control); group 2 (streptozocin (STZ)); group 3 (BV-treated); and group 4 (BMSC-treated). Diabetes mellitus was induced via an intraperitoneal (IP) injection of STZ in the rats from groups 2, 3 and 4. Following the diagnosis of DM, the rats in group 3 were injected with a daily dose of 0.5 mg/kg of BV, while the rats in group 4 were treated with a single injection of BMSCs. All rats were euthanized after 4 weeks, and their tongues were dissected and divided into halves. The right halves of the tongues were utilized for the histological examination, followed by morphometric analysis. In contrast, the left halves were used to detect the local gene expression of transforming growth factor beta 1 (TGF-ß1) and vascular endothelial growth factor (VEGF). RESULTS: Group 2 revealed marked disruption in the morphology of the fungiform and filiform papillae, and atrophic epithelial changes in both dorsal and ventral surface epithelium as compared to other groups. Group 4 showed a significantly larger number of taste buds, and a higher gene expression of TGF-ß1 and VEGF as compared to groups 2 and 3. Additionally, BV and BMSCs effectively increased the thickness of dorsal and ventral surface epithelium as compared to group 2. CONCLUSIONS: Treatment with BMSCs was associated with significant improvement in the morphology and number of lingual epithelial cells and taste buds in the tongues of diabetic rats as compared to BV-treated rats, which was due to the local upregulation of TGF-ß1 and VEGF gene expression.

Evaluation of dental pulp stem cells response to flowable nano-hybrid dental composites: A comparative analysis.

BACKGROUND: Flowable resin composites (FRC) are tooth-colored restorative materials that contain a lower filler particle content, and lower viscosity than their bulk counterparts, making them useful for specific clinical applications. Yet, their chemical makeup may impact the cellular population of the tooth pulp. This in-vitro study assessed the cytocompatibility and odontogenic differentiation capacity of dental pulp stem cells (DPSCs) in response to two recent FRC material extracts. METHODS: Extracts of the FRC Aura easyflow (AEF) and Polofil NHT Flow (PNF) were applied to DPSCs isolated from extracted human teeth. Cell viability of DPSCs was assessed using MTT assay on days 1, 3 and 7. Cell migration was assessed using the wound healing assay. DPSCs' capacity for osteo/odontogenic differentiation was assessed by measuring the degree of mineralization by Alizarin Red S staining, alkaline phosphatase enzyme (ALP) activity, and monitoring the expression of osteoprotegerin (OPG), RUNX Family Transcription Factor 2 (RUNX2), and the odontogenic marker dentin sialophosphoprotein (DSPP) by RT-PCR. Monomer release from the FRC was also assessed by High-performance liquid chromatography analysis (HPLC). RESULTS: DPSCs exposed to PNF extracts showed significantly higher cell viability, faster wound closure, and superior odontogenic differentiation. This was apparent through Alizarin Red staining of calcified nodules, elevated alkaline phosphatase activity, and increased expression of osteo/odontogenic markers. Moreover, HPLC analysis revealed a higher release of TEDGMA, UDMA, and BISGMA from AEF. CONCLUSIONS: PNF showed better cytocompatibility and enhancement of odontogenic differentiation than AEF.

Machine learning base models to predict the punching shear capacity of posttensioned UHPC flat slabs.

The aim of this research is to present correction factors for the punching shear formulas of ACI-318 and EC2 design codes to adopt the punching capacity of post tensioned ultra-high-performance concrete (PT-UHPC) flat slabs. To achieve that goal, the results of previously tested PT-UHPC flat slabs were used to validate the developed finite element method (FEM) model in terms of punching shear capacity. Then, a parametric study was conducted using the validated FEM to generate two databases, each database included concrete compressive strength, strands layout, shear reinforcement capacity and the aspect ratio of the column besides the correction factor (the ratio between the FEM punching capacity and the design code punching capacity). The first considered design code in the first database was ACI-318 and in the second database was EC2. Finally, there different "Machine Learning" (ML) techniques manly "Genetic programming" (GP), "Artificial Neural Network" (ANN) and "Evolutionary Polynomial Regression" (EPR) were applied on the two generated databases to predict the correction factors as functions of the considered parameters. The results of the study indicated that all the developed (ML) models showed almost the same level of accuracy in terms of the punching ultimate load (about 96%) and the ACI-318 correction factor depends mainly on the concrete compressive strength and aspect ratio of the column, while the EC2 correction factor depends mainly on the concrete compressive strength and the shear reinforcement capacity.

Eco-friendly extraction of antibacterial compounds from enriched olive pomace: a design-of-experiments approach to sustainability.

The increasing interest in utilizing olive pomace bioactive molecules to advance functional elements and produce antioxidant and antimicrobial additives underscores the need for eco-friendly extraction and purification methods. This study aims to develop an eco-friendly extraction method to evaluate the effect of extraction parameters on the recovery of bioactive molecules from enriched olive pomace. The effects were identified based on total phenolic and flavonoid contents and antioxidant activity, employing a design of experimental methodology. The positive and the negative simultaneous effects showed that among the tested enrichments, those incorporating Nigella Sativa, dates, and coffee demonstrated superior results in terms of the measured responses. Furthermore, chromatographic analysis unveiled the existence of intriguing compounds such as hydroxytyrosol, tyrosol, and squalene in distinct proportions. Beyond this, our study delved into the structural composition of the enriched pomace through FTIR analysis, providing valuable insights into the functional groups and chemical bonds present. Concurrently, antimicrobial assays demonstrated the potent inhibitory effects of these enriched extracts against various microorganisms, underscoring their potential applications in food preservation and safety. These findings highlight enriched olive pomace as a valuable reservoir of bioactive molecules for food products since they can enhance their anti-oxidative activity and contribute to a sustainable circular economy model for olive oil industries.

Optimized spray-dried conditions' impact on fatty acid profiles and estimation of in vitro digestion of spray-dried chia/fish oil microcapsules.

Long-chain polyunsaturated fatty acids (LCPUFA) are of interest due to their potential health properties and have a significant role in reducing the risk of various chronic diseases in humans. It is commonly used as a supplement. However, lipid oxidation is an important negative factor caused by environmental, processing, and limited water solubility of LCPUFA, making them difficult to incorporate into food products. The objective of this research work was to prevent oxidation, extend shelf life, enhance the stability of fatty acids, and to achieve controlled release by preparing spray-dried powder (SDM). For spray-drying, aqueous emulsion blends were formulated using a 1:1 ratio of chia seed oil (CSO) and fish oil (FO) and using a laboratory-scale spray-dryer with varying conditions: inlet air temperature (IAT, 125-185 °C), wall material (WM, 5-25%), pump speed (PS, 3-7 mL/min), and needle speed (NS, 3-11 s). The maximum alpha-linolenic acid (ALA) content was 33 ± 1%. The highest values of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the microcapsules were 8.4 ± 0.4 and 13 ± 1%, respectively. Fourier transform infrared and X-Ray diffraction analysis results indicated that SDM was successfully formulated with Gum Arabic and maltodextrin (MD). The blending without encapsulation of CSO and FO was digested more efficiently and resulted in more oil being released with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and SGF + SIF conditions without heating. No significant changes were observed for saturated, monounsaturated, and LCPUFA, whether exposed or not to gastrointestinal conditions. However, compared to the release of SDM, it can be useful for designing delivery systems for the controlled release of essential fatty acids.

Towards the preparation of sustainable superplasticizers for geopolymeric pastes via radiation-induced grafting of sulfonic group-bearing monomers onto corn starch.

To address escalating environmental and sustainability concerns of petroleum-based superplasticizers (SPs), this work aims to develop sustainable and eco-friendly starch-based SPs using gamma radiation for maintaining the desired workability of geopolymeric pastes. Specifically, two green SPs were prepared from starch via radiation-induced grafting of two sulfonic group-bearing monomers, namely 2-acrylamido-2-methylpropane sulfonic acid (AMPS) and 4-styrene sulfonic acid sodium salt (Na4SS). The grafting reaction was improved by initial modification of starch with glycidyl methacrylate to insert vinyl groups into the starch backbone. The modified starch samples were characterized by a variety of analytical techniques such as FTIR, 1H NMR, EDX, SLS, and viscometry. The prepared SPs exhibited high stability in aqueous 5 % NaOH. The effect of the prepared SPs on the fresh properties of GGBFS/MK geopolymer was studied using the mini slump test, zeta potential, adsorption capacity, and setting time. They significantly improved the paste flowability and dispersion compared to the control. Notably, the aromatic Na4SS-grafted starch displayed a comparable enhancement to the commercial PNS, while outperforming the aliphatic AMPS-grafted sample. This emphasizes the potential of these green SPs to address the challenges posed by the petroleum-based SPs and maximize the benefit of using starch as a green renewable resource.

Insecticidal Activities of Securidaca longepedunculata Fresen Extracts and Feeding Behavior of Schizaphis graminum Rondani: Electropenetrography Approach.

The aphid, Schizaphis graminum Rondani (Hemiptera: Aphididae), is one of the most destructive pests of wheat. It is responsible for significant economic losses in the agricultural sector, with an estimated 45% of wheat fields affected. Plant-based insecticides have seen a rapid increase in popularity in recent years due to their efficacy, cost-effectiveness, biodegradability, and lower toxicity compared to synthetic pesticides. The study aimed to evaluate the toxic potential of S. longipedunculata extracts against S. graminum and investigate the insect's feeding behavior on wheat. Initially macerated in methanol, the different extracts of S. longipedunculata organs were fractionated using n-hexane, chloroform, ethyl acetate, and butanol. The feeding behavior was analyzed by comparing the waveforms generated by the EPG with the control. After 72 h of treatment, the ethyl acetate fraction extracted from root had the highest toxicity against aphids, with mean 26 mortality of S. graminum at LC50 of 330 ppm; 25 mortality S. graminum at LC50 of 400 ppm for leaves; and mean 24.5 mortality S. graminum at LC50 of 540 ppm in stem bark. EPG analysis indicated that the extract fractions enhanced plant tissue resistance by significantly preventing aphid access to the phloem. The toxic effect of the botanical extracts significantly enhanced the chemical composition of the leaf medium, resulting in a drastic reduction in the number of tissue attacks by S. graminum. In summary, besides their toxicity to S. graminum, extracts of S. longipedunculata reinforce the plant's defense mechanisms, significantly reducing the S. graminum population. They also reinforce wheat's defense mechanisms. S. longipedunculata can, therefore, be used as a promising agent in the biological control of S. graminum.

Sedative and muscle relaxant activities of diterpenoids from Phlomidoschema parviflorum

Abstract Phlomidoschema parviflorum (Benth.) Vved. (Basionym: Stachys parviflora Benth.) Lamiaceae, have significance medicinal importance as it is used in number of health disorders including diarrhea, fever, sore mouth and throat, internal bleeding, weaknesses of the liver and heart genital tumors, sclerosis of the spleen, inflammatory tumors and cancerous ulcers. The present contribution deals with the sedative and muscle relaxant like effects of diterpenoids trivially named stachysrosane and stachysrosane, isolated from the ethyl acetate soluble fraction of P. parviflorum. Both compounds (at 5, 10 and 15 mg/kg, i.p) were assessed for their in vivo sedative and muscle relaxant activity in open field and inclined plane test, respectively. The geometries of both compounds were optimized with density functional theory. The molecular docking of both compounds were performed with receptor gamma aminobutyric acid. Both compounds showed marked activity in a dose dependent manner. The docking studies showed that both compounds interact strongly with important residues in receptor gamma aminobutyric acid. The reported data demonstrate that both compounds exhibited significant sedative and muscle relaxant-like effects in animal models, which opens a door for novel therapeutic applications.