INFLUENCE OF SOME GROWTH SUBSTANCES AND CHEMICAL FERTILIZATION ON FLOWERING AND CHEMICAL COMPOSITION OF MATTHIOLA INCANA L. PLANT

Two field trials were conducted during two successive seasons of 2018/2019 and 2019/2020 in the Floriculture Farm of Horticulture Department, Faculty of Agriculture, Benha University, Egypt to study the effects of spraying with some growth substances (kinetin, salicylic acid, calcium thiosulfate and potassium silicate) and chemical fertilization (N.P.K) as well as their combinations on flowering and some chemical constituents of Matthiola incana L. plants to enhance flowering quality for gardens bed ornamentation. The obtained results showed that spraying plants with 100 ppm kinetin in addition to NPK fertilization at the highest level (100 N: 200 P: 200 K kg/fed) resulted in the highest values in both seasons in case of fresh and dry weights of inflorescence and flowering portion, length and diameter of the flowering portion, number, diameter and fresh weight of florets, flowering duration, leaf total chlorophylls and total indoles content. This treatment, on the other hand, recorded the lowest values of leaves total phenols content. Conclusively, it is recommended to spray Matthiola incana L. plants with kinetin at 100 ppm supplemented with NPK chemical fertilization at 100 N: 200 P: 200 K kg/fed to obtain the best flowering quality for expor

EFFECT OF SOME GROWTH SUBSTANCES AND CHEMICAL FERTILIZATION ON VEGETATIVE GROWTH AND CHEMICAL COMPOSITION OF MATTHIOLA INCANA L. PLANT

A field experiment was carried out during two successive seasons of 2018/2019 and 2019/2020 in the Floriculture Farm of the Horticulture Department, Faculty of Agriculture, Benha University, Egypt to study the effects of spraying some growth substances (kinetin, salicylic acid, calcium thiosulfate and potassium silicate as well as, N.P.K chemical fertilization) on vegetative growth and chemical composition of Matthiola incana plants to increase and improve the quality of this plant as a bed gardens ornamentation. The obtained results showed that the tallest plants and the thickest plant stems were recorded by 100 ppm kinetin combined with NPK fertilization at high level treatment in both seasons. The heaviest fresh and dry weights of leaves/plant were recorded by 100 ppm kinetin-sprayed plants enriched with NPK fertilization at the highest level in both seasons. The highest number of branches and leaves/plant were recorded by 100 ppm kinetin-sprayed plants combined with NPK fertilization at high level in both seasons. The highest leaf N and total carbohydrates % were recorded by 100 ppm kinetin- sprayed plants provided with NPK fertilization at the highest level, whereas the richest leaf P % was registered by 200 ppm salicylic-sprayed plants combined with NPK fertilization at the highest level. While, the greatest leaf K % was scored by 6 cm3 potassium silicate-sprayed plants, supplemented with NPK fertilization at the highest level in both seasons. Conclusively, spraying Matthiola incana plants with kinetin at 100 ppm in addition to chemical fertilizer at 100 N: 200 P: 200 K kg/fed produced the best vegetative growth and quality of this plan

Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents

In this article, we display on the synthesis and biological evaluation of a new series of thiazolylpyrimidine 3a-l and thiazolidinylpyrimidine derivatives 5a-e. The structures of the new compounds were confirmed by using different spectral techniques including NMR, IR, mass spectroscopy in addition to elemental analyses. The cell viability of the new compounds was assessed against normal human mammary gland epithelial (MCF-10A) cell line. Data revealed that none of the compounds examined exhibited cytotoxic effects, and the cell viability for the compounds examined at 50 µM was greater than 87%. The antiproliferative activity of 3a-l and 5a-e was evaluated against four human cancer cell lines where the compounds showed promising activity. The most potent derivatives were compounds 3a, 3c, 3f, 3i, and 5b with GI$_{50}$ values ranging from 0.90 µM to 1.70 µM against the four cancer cell lines in comparison to doxorubicin (GI$_{50}$ = 1.10 µM). Compounds 3a, 3c and 3i showed potent antiproliferative activity with dual inhibitory action against EGFR and BRAF$^{V600E}$. Compounds 3a, 3c, and 3i demonstrated promising AutoDock scores towards EGFR and BRAF$^{V600E}$ with values of − 9.1 and − 8.6, −9.0 and − 8.5, and − 8.4 and − 8.0 kcal/mol, respectively. The physicochemical and pharmacokinetic characteristics of 3a, 3c, and 3i were anticipated, demonstrating their oral bioavailability

Design, Synthesis and Biological Evaluation of Syn and Anti-like Double Warhead Quinolinones Bearing Dihydroxy Naphthalene Moiety as Epidermal Growth Factor Receptor Inhibitors with Potential Apoptotic Antiproliferative Action

Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a–e and 7a–e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a–e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal–Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a–e and 7a–e were evaluated. Compounds 4a–e and 7a–e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI50 ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI50 of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC50 values ranging from 64 nM to 97 nM. Compounds 4a, 4b, and 7d demonstrated potent apoptotic effects via their effects on caspases 3, 8, 9, Cytochrome C, Bax, and Bcl2. Finally, docking studies show the relevance of the free amino group of the quinoline moiety for antiproliferative action via hydrogen bond formation with essential amino acids

A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma

© 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the Creative Commons Attribution-Non Commercial-No Derivatives CC BY-NC-ND licence, https://creativecommons.org/licenses/by-nc-nd/4.0/Tumor microenvironment is an intricate web of stromal and immune cells creating an immune suppressive cordon around the tumor. In hepatocellular carcinoma (HCC), Tumor microenvironment is a formidable barrier towards novel immune therapeutic approaches recently evading the oncology field. In this study, the main aim was to identify the intricate immune evasion tactics mediated by HCC cells and to study the epigenetic modulation of the immune checkpoints; Programmed death-1 (PD-1)/ Programmed death-Ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT)/Cluster of Differentiation 155 (CD155) at the tumor-immune synapse. Thus, liver tissues, PBMCs and sera were collected from Hepatitis C Virus (HCV), HCC as well as healthy individuals. Screening was performed to PD-L1/PD-1 and CD155/TIGIT axes in HCC patients. PDL1, CD155, PD-1 and TIGIT were found to be significantly upregulated in liver tissues and peripheral blood mononuclear cells (PBMCs) of HCC patients. An array of long non-coding RNAs (lncRNAs) and microRNAs validated to regulate such immune checkpoints were screened. The lncRNAs; CCAT-1, H19, and MALAT-1 were all significantly upregulated in the sera, PBMCs, and tissues of HCC patients as compared to HCV patients and healthy controls. However, miR-944–5p, miR-105–5p, miR-486–5p, miR-506–5p, and miR-30a-5p were downregulated in the sera and liver tissues of HCC patients. On the tumor cell side, knocking down of lncRNAs—CCAT-1, MALAT-1, or H19—markedly repressed the co-expression of PD-L1 and CD155 and accordingly induced the cytotoxicity of co-cultured primary immune cells. On the immune side, ectopic expression of the under-expressed microRNAs; miR-486–5p, miR-506–5p, and miR-30a-5p significantly decreased the transcript levels of PD-1 in PBMCs with no effect on TIGIT. On the other hand, ectopic expression of miR-944–5p and miR-105–5p in PBMCs dramatically reduced the co-expression of PD-1 and TIGIT. Finally, all studied miRNAs enhanced the cytotoxic effects of PBMCs against Huh7 cells. However, miR-105–5p showed the highest augmentation for PBMCs cytotoxicity against HCC cells. In conclusion, this study highlights a novel co-targeting strategy using miR-105–5p mimics, MALAT-1, CCAT-1 and H19 siRNAs to efficiently hampers the immune checkpoints; PD-L1/PD-1 and CD155/TIGIT immune evasion properties in HCC.Peer reviewe

Aiming at the global elimination of viral hepatitis:challenges along the care continuum

Abstract A recent international workshop, organized by the authors, analyzed the obstacles facing the ambitious goal of eliminating viral hepatitis globally. We identified several policy areas critical to reaching elimination targets. These include providing hepatitis B birth-dose vaccination to all infants within 24 hours of birth, preventing the transmission of blood-borne viruses through the expansion of national hemovigilance schemes, implementing the lessons learned from the HIV epidemic regarding safe medical practices to eliminate iatrogenic infection, adopting point-of-care testing to improve coverage of diagnosis, and providing free or affordable hepatitis C treatment to all. We introduce Egypt as a case study for rapid testing and treatment scale-up: this country offers valuable insights to policy makers internationally, not only regarding how hepatitis C interventions can be expeditiously scaled-up, but also as a guide for how to tackle the problems encountered with such ambitious testing and treatment programs.</jats:p

Prediction of survival among patients receiving transarterial chemoembolization for hepatocellular carcinoma: A response-based approach

Background and aims: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. Approach and results: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. Conclusions: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognosticatio