Search

This paper presents a control strategy synthesis method for dynamical systems with differential constraints, emphasizing the prioritization of specific rules. Special attention is given to scenarios where not all rules can be simultaneously satisfied to complete a given task, necessitating decisions on the extent to which each rule is satisfied, including which rules must be upheld or disregarded. We propose a learning-based Model Predictive Control (MPC) method designed to address these challenges. Our approach integrates a learning method with a traditional control scheme, enabling the controller to emulate human expert behavior. Rules are represented as Signal Temporal Logic (STL) formulas. A robustness margin, quantifying the degree of rule satisfaction, is learned from expert demonstrations using a Conditional Variational Autoencoder (CVAE). This learned margin is then applied in the MPC process to guide the prioritization or exclusion of rules. In a track driving simulation, our method demonstrates the ability to generate behavior resembling that of human experts and effectively manage rule-based dilemmas. [ABSTRACT FROM AUTHOR]

Herein, the apoptotic mechanism of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) was examined in cisplatin-resistant lung cancer cells. PGG significantly reduced viability; increased sub-G1 accumulation and the number of terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL)-positive cells; induced the cleavage of poly (ADP-ribose) polymerase (PARP), caspases (8,9,3,7), B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN); and attenuated the expression of p-AKT, X-linked inhibitor of apoptosis protein (XIAP), Bcl-2, Bcl-xL and survivin in A549/cisplatin-resistant (CR) and H460/CR cells. Notably, PGG activated p53, p-checkpoint kinase 2 (CHK2) and p-H2A histone family member X (p-H2AX), with increased levels of DNA damage (DSBs) evaluated by highly expressed pH2AX and DNA fragmentation registered on comet assay, while p53 knockdown reduced the ability of PGG to reduce viability and cleave caspase 3 and PARP in A549/CR and H460/CR cells. Additionally, PGG treatment suppressed the growth of H460/CR cells in Balb/c athymic nude mice with increased caspase 3 expression compared with the cisplatin group. Overall, PGG induces apoptosis in cisplatin-resistant lung cancer cells via the upregulation of DNA damage proteins such as γ-H2AX, pCHK2 and p53. [ABSTRACT FROM AUTHOR]

Herein, apoptotic mechanism of Moracin D was explored in prostate cancer cells in association with peroxisome proliferator‐activated receptor gamma (PPAR‐γ)‐related signaling involved in lipid metabolism. Moracin D augmented cytotoxicity and sub G1 population in PC3 and DU145 prostate cancer cells, while DU145 cells were more susceptible to Moracin D than PC3 cells. Moracin D attenuated the expression of caspase‐3, poly (ADP‐ribose) polymerase (PARP), B‐cell lymphoma 2 (Bcl‐2), and B‐cell lymphoma‐extra‐large (Bcl‐xL) in DU145 cells. Consistently, Moracin D significantly augmented the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)‐positive cells in DU145 cells. Interestingly, Moracin D activated PPAR‐γ and phospho‐protein kinase C delta (p‐PKC‐δ) and inhibited phospho‐protein kinase C alpha (p‐PKC‐α) in DU145 cells. Furthermore, STRING bioinformatic analysis reveals that PPAR‐γ interacts with nuclear factor‐κB (NF‐κB) that binds to PKC‐α/PKC‐δ or protein kinase B (AKT) or extracellular signal–regulated kinase (ERK). Indeed, Moracin D decreased phosphorylation of NF‐κB, ERK, and AKT in DU145 cells. Conversely, PPAR‐γ inhibitor GW9662 reduced the apoptotic ability of Moracin D to activate caspase 3 and PARP in DU145 cells. Taken together, these findings provide a novel insight that activation of PPAR‐γ/p‐PKC‐δ and inhibition of p‐PKC‐α are critically involved in Moracin D–induced apoptosis in DU145 prostate cancer cells. [ABSTRACT FROM AUTHOR]

Though Sanggenon G (SanG) from root bark of Morus alba was known to exhibit anti‐oxidant and anti‐depressant effects, its underlying mechanisms still remain unclear. Herein SanG reduced the viability of A549 and H1299 non‐small lung cancer cells (NSCLCs). Also, SanG increased sub‐G1 population via inhibition of cyclin D1, cyclin E, CDK2, CDK4 and Bcl‐2, cleavages of poly (ADP‐ribose) polymerase (PARP) and caspase‐3 in A549 and H1299 cells. Of note, SanG effectively inhibited c‐Myc expression by activating ribosomal protein L5 (RPL5) and reducing c‐Myc stability even in the presence of cycloheximide and 20% serum in A549 cells. Furthermore, SanG enhanced the apoptotic effect with doxorubicin in A549 cells. Taken together, our results for the first time provide novel evidence that SanG suppresses proliferation and induces apoptosis via caspase‐3 activation and RPL5 mediated inhibition of c‐Myc with combinational potential with doxorubicin. [ABSTRACT FROM AUTHOR]

Since heat shock protein (HSP27) is a prognostic marker in cervical cancer, in the present study, the apoptotic mechanism of lambertianic acid (LA) was investigated in human cervical cancers in association with HSP27/STAT3/AKT signaling axis. LA exerted significant cytotoxicity, induced sub‐G1 population, and increased the cleavage of Poly (ADP‐ribose) polymerase (PARP) and cysteine aspartyl‐specific protease 3 (caspase3) in HeLa and Caski cancer cells. Consistently, LA downregulated anti‐apopotic genes such as B‐cell lymphoma 2 (Bcl‐2) and inhibitors of apoptosis proteins (c‐IAP) in HeLa and Caski cells. Furthermore, LA‐inhibited phosphorylation of HSP27, signal transducer, and activator of transcription 3 (STAT3) and Protein kinase B (AKT) through disturbing the binding of HSP27 with STAT3 or AKT in HeLa cells. Notably, LA upregulated the level of miR216b in HeLa and Caski cells. Consistently, miR216b mimic suppressed phosphorylation of HSP27 and reduced the expression of pro‐PARP, while miR216b inhibitor reversed the ability of LA to attenuate phosphorylation of AKT, HSP27, and STAT3 and to reduce the expression of pro‐PARP in HeLa cells. Overall, our findings suggest that miRNA216b mediated inhibition of HSP27/STAT3/ AKT signaling axis is critically involved in LA‐induced apoptosis in cervical cancers. [ABSTRACT FROM AUTHOR]

Though honokiol, derived from the Magnolia tree, was known to suppress renal fibrosis, pulmonary fibrosis, non‐alcoholic steatoheptitis, inflammation and cancers, the underlying antifibrotic mechanisms of honokiol are not fully understood in hepatic stellate cells until now. Thus, in the present study, inhibitory mechanism of honokiol on liver fibrosis was elucidated mainly in hepatic stellate cells (HSCs) by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, cell cycle analysis and western‐blotting. Honokiol exerted cytotoxicity in LX‐2, HSC‐T6 and Hep‐G2 cells. Honokiol increased sub G1 population and activated caspase 3 and cleaved poly (ADP‐ribose) polymerase (PARP) in HSCs. Moreover, honokiol attenuated the expression of alpha smooth muscle actin (α‐SMA), transforming growth factor beta 1 (TGF‐β1), phospho‐Smad3, phospho‐AKT, cyclin D1, c‐Myc, Wnt3a, β‐catenin, and activated phosphorylation of glycogen synthase kinase 3 beta (GSK3β) in HSCs. Conversely, GSK3β inhibitor SB216763 reversed the effect of honokiol on PARP, α‐SMA, phospho‐GSK3β, β‐catenin and sub G1 population in LX‐2 cells. Overall, honokiol exerts apoptotic and antifibrotic effects via activation of GSK3β and inhibition of Wnt3a/β‐catenin signalling pathway. [ABSTRACT FROM AUTHOR]

In the current study, the function of long noncoding RNA (LncRNA) RAB5IF was elucidated in hepatocellular carcinoma (HCCs) in association with LGR5 related signaling. Here TCGA analysis revealed that LncRNA RAB5IF was overexpressed in HCC, and its overexpression level was significantly (p < 0.05) correlated with poor prognosis in patients with HCC. Furthermore, LncRNA RAB5IF depletion suppressed cell proliferation and colony formation, increased sub G1 population, cleavage of poly ADP-ribose polymerase (PARP) and cysteine aspartyl-specific protease (caspase 3) and attenuated the expression of procaspase 3, pro-PARP and B-cell lymphoma 2 (Bcl-2) in HepG2 and Hep3B cells. Furthermore, LncRNA RAB5IF depletion reduced the expression of LGR5 and its downstreams such as β-catenin and c-Myc in HepG2 and Hep3B cells. Notably, LGR5 depletion also attenuated the expression of pro-PARP, pro-caspase3, β-catenin and c-Myc in HepG2 and Hep3B cells. Conversely, LGR5 overexpression upregulated β-catenin and c-Myc in Alpha Mouse Liver 12 (AML-12) normal hepatocytes. Overall, these findings provide novel evidence that LncRNA RAB5IF promotes the growth of hepatocellular carcinoma cells via LGR5 mediated β-catenin and c-Myc signaling as a potent oncogenic target. [ABSTRACT FROM AUTHOR]