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Purpose The aim of this study was to determine the expression of Bak, Bax, Bcl-2, Bcl-xl and procaspase-3 proteins in colorectal tumor and regional lymph nodes, as well as to investigate the correlation between them and with clinicopathologic parameters. Methods Expression of the examined proteins was evaluated by immunohistochemical study. Results No significant correlation was revealed between Bcl-2, Bcl-xl, Bak, Bax and procaspase-3 expressions and age, gender, location or size of primary tumor and grade in the main tumor mass or in lymph nodes. Additionally, the only association we found was between Bak protein in primary tumor and in adjacent metastatic lymph nodes. Conclusion Bcl-2 protein seems to exert substantial effects prevention of apoptosis in pT3 CRC with positive lymph node involvement, while lower expressions of Bcl-xl proteins suggest that it does not play a significant part in the inhibition of apoptosis. [ABSTRACT FROM AUTHOR]

In this paper a scenario-based Distributed Model Predictive Control (DMPC) approach based on a reduced scenario tree is developed for large-scale freeway networks. In the new scenario-based DMPC approach, uncertainties in a large-scale freeway network are distinguished into two categories: global uncertainties for the overall network and local uncertainties applicable to subnetworks only. We propose to use a reduced scenario tree instead of using a complete scenario tree. A complete scenario tree is defined as a scenario tree consisting of global scenarios and all the combinations of the local scenarios for all subnetworks, while a reduced scenario tree is defined as a scenario tree consisting of global scenarios and a reduced local scenario tree in which local scenarios are combined within each subnetwork, not among subnetworks. Moreover, an expected-value setting and a min–max setting are considered for handling uncertainties in scenario-based DMPC. In the expected-value setting, the expected-value of the cost function values for all considered uncertainty scenarios is optimized by scenario-based DMPC. However, in the min–max setting, the worst-case of the cost function values for all considered uncertainty scenarios is optimized by scenario-based DMPC. The results for a numerical experiment show that the new scenario-based DMPC approach is effective in improving the control performance while at the same time satisfying the queue constraints in the presence of uncertainties. Additionally, the proposed approach results in a relatively low computational burden compared to the case with the complete scenario tree. [ABSTRACT FROM AUTHOR]

Isorhapontigenin (ISO), a naturally-occurring stilbene derivative, has garnered significant attention due to its potent anticancer and anti-inflammatory properties. This review synthesizes current knowledge regarding the mechanisms of action, efficacy, and potential therapeutic applications of Isorhapontigenin acquired in vitro and in vivo. It systematically analyzes its effects on various cancer cell lines, tumor models, and inflammatory conditions, examining its impact on cell proliferation, apoptosis, metastasis, and inflammatory mediators. In vitro studies reveal that Isorhapontigenin induces cell cycle arrest, promotes apoptosis, and inhibits cancer cell migration through modulation of key signaling pathways, including EGFR-PI3K-Akt and NF-κB. It also demonstrates potent antioxidant and anti-inflammatory effects by enhancing Nrf2 signaling and suppressing pro-inflammatory cytokine production. These findings are corroborated by in vivo studies confirming its ability to inhibit tumor growth in xenograft models and attenuate inflammatory responses in various disease models. Notably, Isorhapontigenin exhibits superior pharmacokinetic profiles then resveratrol, with higher oral bioavailability. Isorhapontigenin demonstrates multi-target actions, including epigenetic modulation through microRNA regulation, which highlight its potential as a versatile therapeutic agent. This review also identifies current limitations in Isorhapontigenin research that require further investigation. Overall, Isorhapontigenin offers promise as a multi-faceted compound for the treatment of cancer, inflammatory diseases, and metabolic disorders, providing a solid foundation for future research and potential clinical applications. [Display omitted] • Isorhapontigenin (ISO), a naturally occurring stilbene derivative with multifunctional activity. • ISO induces apoptosis of cancer cells through modulation of key signaling pathways. • ISO shows anti-inflammatory properties by inhibiting cytokine production. • ISO shows biological effect in vitro and in vivo model. [ABSTRACT FROM AUTHOR]

[Display omitted] In the study, we aimed to investigate the activity of nanoformulations containing 5-fluorouracil and polymer-magnetic hybrids bearing membrane-penetrating and ligand-receptor-recognizing agents against colorectal cancer cells. The formation and characterization of iron oxide particles covered with polymeric shells comprising lithocholic acid and folic acid moieties are presented. The efficiency of nanoformulations combined by the simple mixing of low doses of 5-fluorouracil with the obtained hybrids was demonstrated against DLD-1 and HT-29 colon cancer cells. The most pronounced cytotoxic potential against HT-29 cells was observed in the cases of particles based on block and randomly arranged copolymers functionalized by FA motifs with depletion of viable cells by approximately 50 % compared to control cells and cells treated by 5-FU applied in free form. In the case of the DLD-1 cell line, the percentage of viable DLD-1 cells decreased by about 30 to 40% after treatment with the block and randomly arranged copolymer decorated by FA-moiety, when compared to 5-FU at the free form and the untreated control. The induction of apoptosis associated with PS-translocation was determined to be the main mechanism of their cytotoxic effects. Moreover, the safety profiles of the nanoformulations were established through hemolysis assay and the analysis of the viability of human colorectal fibroblasts. It was indicated that all tested nanoparticles met the compatibility requirements at the in vitro level. It should be emphasized that in many cases, there was a significant improvement in the compatibility of hybrids with the FA motif compared to non-functionalized hybrids with the addition of 5-FU. These findings suggest that the presence of FA might modulate the toxicity of chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

The Plectranthus genus is often cited for its medicinal properties. Plectranthus ornatus Codd. is traditionally used in Africa for the treatment of gastric and liver diseases and their leaves are used for their antibiotic action. The main constituent of P. ornatus is the halimane compound, 11 R ∗−acetoxyhalima−5,13 E −dien−15−oic acid (Hal), described for its antimicrobial and anticancer properties. The objective of this work was to improve the activity of the halimane lead molecule. Further physiochemical characterisation was performed on Hal. To the best of our knowledge, this work constitutes the first published data of the absolute configurations by SCXRD and thermal stability of Hal. Using Hal , reactions with different amines were carried out to afford novel semi-synthetic derivatives and their structural elucidation was completed. The cytotoxicity of the derivatives was assessed against three leukaemia cancer cell lines (CCRF-CEM, K562 and HL-60). The antioxidant activity was investigated using H 2 O 2 -induced HGF-1 cells and their anti-inflammatory activity was studied using RT-PCR and ELISA. Our data showed that amide derivatives of Hal presented moderate cytotoxicity and more potent activity when compared to the parent molecule, giving insight into the SAR of Hal. The derivatives also displayed protection against oxidative damage to DNA. Finally, the derivatives possessed anti-inflammatory properties at the level of gene and protein expression for the cytokines IL-1β , TNF-α and IL-6 , induced by LPS in normal HGF-1 cells. Overall, our study provides useful insight into the enhanced biological activities of semi-synthetic Hal derivatives, as a starting point for novel drug formulations in cancer therapy. [Display omitted] • Plectranthus ornatus Codd. traditionally used for its medicinal properties. • Halimane diterpene (Hal) from P. ornatus shows biological activity in cancer cell lines. • Semi-synthetic amide derivatives of Hal demonstrate improved cytotoxicity. • Amide derivatives also showed anti-oxidant and anti-inflammatory activity. • Analogues of Hal diterpene exhibit potential for novel therapeutic drug leads. [ABSTRACT FROM AUTHOR]

Three new arene ruthenium(II) complexes have been obtained. Their cytotoxic studies showed them to display moderate activity, however evaluation of their DNA damage percentage in NALM-6 cells by a comet assay indicated that the analyzed ruthenium(II) complexes triggered DNA damage. A series of arene ruthenium(II) complexes, 1a - 3a , with the general formula [(η6-arene)Ru(L)Cl 2 ] (where arene = p- cymene, hexamethylbenzene and benzene, respectively, and L = 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridyl)-1 H -pyrazole-4-carboxylic acid methyl ester) were synthesized and characterized by elemental analysis, MS, IR and 1H NMR spectroscopy. The stability of selected complexes was assessed by UV–Vis spectroscopy over 24 and 48 hour periods. The synthesized complexes were evaluated for in vitro experiments using HL-60, NALM-6, WM-115 and COLO-205, and they showed low cytotoxic activity. The most active compound, 2a , possesses IC 50 = 41.17 ± 3.68 µM, which is comparable to the reference compound quercetin. X-ray crystallographic analysis of compound 1a found that the ruthenium complex adopts a piano-stool type of geometry, with crystal packing stabilized by a 3-D net of O H...Cl and C H...Cl type hydrogen bonds, the latter forming dimers in the crystal lattice. The most active complexes in the cytotoxicity experiments were selected for evaluation of the damage percentage in NALM-6 cells by a comet assay: the extent of DNA fragmentation in the lymphoblastic leukemia cells indicated that the analyzed ruthenium(II) complexes triggered DNA damage. [ABSTRACT FROM AUTHOR]

Model Predictive Control (MPC) is one of the most advanced real-time control techniques that has been widely applied to Water Resources Management (WRM). MPC can manage the water system in a holistic manner and has a flexible structure to incorporate specific elements, such as setpoints and constraints. Therefore, MPC has shown its versatile performance in many branches of WRM. Nonetheless, with the in-depth understanding of stochastic hydrology in recent studies, MPC also faces the challenge of how to cope with hydrological uncertainty in its decision-making process. A possible way to embed the uncertainty is to generate an Ensemble Forecast (EF) of hydrological variables, rather than a deterministic one. The combination of MPC and EF results in a more comprehensive approach: Multi-scenario MPC (MS-MPC). In this study, we will first assess the model performance of MS-MPC, considering an ensemble streamflow forecast. Noticeably, the computational inefficiency may be a critical obstacle that hinders applicability of MS-MPC. In fact, with more scenarios taken into account, the computational burden of solving an optimization problem in MS-MPC accordingly increases. To deal with this challenge, we propose the Adaptive Control Resolution (ACR) approach as a computationally efficient scheme to practically reduce the number of control variables in MS-MPC. In brief, the ACR approach uses a mixed-resolution control time step from the near future to the distant future. The ACR-MPC approach is tested on a real-world case study: an integrated flood control and navigation problem in the North Sea Canal of the Netherlands. Such an approach reduces the computation time by 18% and up in our case study. At the same time, the model performance of ACR-MPC remains close to that of conventional MPC. [ABSTRACT FROM AUTHOR]