Search

This paper investigates the impact of cognitive load on the formation and maintenance of cooperation within a public goods game experiment featuring a punishment option. By integrating the experimental designs of prior studies and manipulating cognitive load through the memorization of numbers with varying digits, we reveal that high cognitive load accelerates the breakdown of cooperation, irrespective of the presence of a punishment system. Furthermore, under high cognitive load, participants are more likely to engage in antisocial punishment, while the punishment of free riders remains unaffected. These findings suggest that increased cognitive load depletes the cognitive resources needed for deliberative decision-making, leading to a higher propensity for antisocial punishment. Our study contributes to the literature by demonstrating the significant influence of cognitive load on cooperative behavior and providing new insights into the causes of antisocial punishment. [ABSTRACT FROM AUTHOR]

Combining phytochemicals with chemotherapeutic drugs has demonstrated the potential to surmount drug resistance. In this paper, we explore the efficacy of pentagalloyl glucose (PGG) in modulating P-gp and reversing multidrug resistance (MDR) in drug-resistant leukemic cells (K562/ADR). The cytotoxicity of PGG was evaluated using a CCK-8 assay, and cell apoptosis was assessed using flow cytometry. Western blotting was used to analyze protein expression levels. P-glycoprotein (P-gp) activity was evaluated by monitoring the kinetics of P-gp-mediated efflux of pirarubicin (THP). Finally, molecular docking, molecular dynamics simulation, and molecular mechanics with generalized Born and surface area solvation (MM-GBSA) calculation were conducted to investigate drug–protein interactions. We found that PGG selectively induced cytotoxicity in K562/ADR cells and enhanced sensitivity to doxorubicin (DOX), indicating its potential as a reversal agent. PGG reduced the expression of P-gp and its gene transcript levels. Additionally, PGG inhibited P-gp-mediated efflux and increased intracellular drug accumulation in drug-resistant cells. Molecular dynamics simulations and MM-GBSA calculation provided insights into the binding affinity of PGG to P-gp, suggesting that PGG binds tightly to both the substrate and the ATP binding sites of P-gp. These findings support the potential of PGG to target P-gp, reverse drug resistance, and enhance the efficacy of anticancer therapies. [ABSTRACT FROM AUTHOR]

ABSTRACTInhibition of cluster of differentiation 44 (CD44), a pancreatic cancer stem cell (CSC) marker, is a potential treatment for pancreatic ductal adenocarcinoma (PDAC). In this study, we evaluated the effect of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), a gallotannin contained in various medicinal plants, on CD44 standard (CD44s) and CD44 variant 3 (CD44v3) in Mia-PaCa-2, human pancreatic cancer cells and explored the underlying mechanisms. PGG showed cytotoxic effects and inhibited the proliferation of Mia-PaCa-2 cells. It also inhibited clonogenic activity, adhesion to fibronectin, and cell migration, which are characteristics of CSCs. PGG inhibited the expression of CD44s and CD44v3 by inducing the phosphorylation of p53 and suppressing NF-κB and Foxo3. Inhibition of Foxo3 induces CD44v3 ubiquitination. Indeed, PGG increased proteasome activity and promoted CD44v3 ubiquitination. PGG downregulated the CSC regulatory factors Nanog, Oct-4, and Sox-2, which act downstream of CD44v3 signaling. These data indicate that PGG may have therapeutic effects in pancreatic cancer mediated by inhibition of CSC markers.

Inhibition of cluster of differentiation 44 (CD44), a pancreatic cancer stem cell (CSC) marker, is a potential treatment for pancreatic ductal adenocarcinoma (PDAC). In this study, we evaluated the effect of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), a gallotannin contained in various medicinal plants, on CD44 standard (CD44s) and CD44 variant 3 (CD44v3) in Mia-PaCa-2, human pancreatic cancer cells and explored the underlying mechanisms. PGG showed cytotoxic effects and inhibited the proliferation of Mia-PaCa-2 cells. It also inhibited clonogenic activity, adhesion to fibronectin, and cell migration, which are characteristics of CSCs. PGG inhibited the expression of CD44s and CD44v3 by inducing the phosphorylation of p53 and suppressing NF-κB and Foxo3. Inhibition of Foxo3 induces CD44v3 ubiquitination. Indeed, PGG increased proteasome activity and promoted CD44v3 ubiquitination. PGG downregulated the CSC regulatory factors Nanog, Oct-4, and Sox-2, which act downstream of CD44v3 signaling. These data indicate that PGG may have therapeutic effects in pancreatic cancer mediated by inhibition of CSC markers. [ABSTRACT FROM AUTHOR]

Sanctioning institutions widely exist in human society. Although these institutions play an important role in the management of social affairs, sanctions are often seen to be costly in terms of both time and money. To enable sanctioning institutions to develop effective sanctions, we propose a negative feedback punishment approach for these institutions that combines the feedback control principle and the negative correlation principle. In the negative feedback punishment approach, the punishment intensity imposed on the group is negatively correlated with the current group cooperation proportion. Through evolutionary simulation and theoretical analysis, we found that the negative feedback punishment approach facilitates more stable, time-saving and low-cost performance by sanctioning institutions than other punishment methods. This work offers a feasible solution for sanctioning institutions to solve social dilemmas and provides a possible theoretical starting point for investigating effective pool punishment measures. [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]

1,2,3,4,6-Penta-O-Galloyl-β-d-Glucose (PGG) is a hydrolysable tannin that belongs to the group of gallotannins but also participates in the formation of ellagitannins. PGG is composed of five galloyl groups with a glucose at its core and has structural characteristics that confer a high biological power. In this paper, we describe the chemistry of PGG, which is analyzed from a critical point regarding the types of synthesis, new sources of production from plants and by-products, highlighting the PGG obtaining, and its main functional properties recently reported in scientific literature. PGG has attracted attention because of its therapeutic potential and has shown functional properties as antimicrobial, anti-inflammatory, anti-carcinogenic, antidiabetic and antioxidant. Bioconversion from tannic acid can be potentialized with the use of biotechnological techniques. PGG can be obtained from natural sources as by-products. Research should continue to obtain pure molecules, in adequate quantity and with great biological activity.

Public good games are a metaphor for modeling cooperative behavior in groups in the presence of incentives to free ride. In the model presented here agents play a public good game with their neighbors in a social network structure. Agents' decision rules in our model are inspired by elementary learning observed in laboratory and online behavioral experiments involving human participants with the same amount of information, i.e., when individuals only know their own current contribution and their own cumulated payoff. In addition, agents in the model are allowed to severe links with groups in which their payoff is lower and create links to a new randomly chosen group. Reinforcing the results obtained in network scenarios where agents play Prisoner's Dilemma games, we show that thanks to this relinking possibility, the whole system reaches higher levels of average contribution with respect to the case in which the network cannot change. Our setup opens new frameworks to be investigated, and potentially confirmed, through controlled human experiments.

Our previous study showed that pentagalloylglucose (PGG), a naturally occurring hydrolyzable phenolic tannin, possesses significant anti-rabies virus (RABV) activity. In BHK-21 cells, RABV induced the overactivation of signal transducer and activator of transcription 3 (STAT3) by suppressing the expression of suppressor of cytokine signaling 3 (SOCS3). Inhibition of STAT3 by niclosamide, small interfering RNA, or exogenous expression of SOCS3 all significantly suppressed the replication of RABV. Additionally, RABV-induced upregulation of microRNA 455-5p (miR-455-5p) downregulated SOCS3 by directly binding to the 3= untranslated region (UTR) of SOCS3. Importantly, PGG effectively reversed the expression of miR-455-5p and its following SOCS3/STAT3 signaling pathway. Finally, activated STAT3 elicited the expression of interleukin-6 (IL-6), thereby contributing to RABV-associated encephalomyelitis; however, PGG restored the level of IL-6 in vitro and in vivo in a SOCS3/STAT3-dependent manner. Altogether, these data identify a new miR-455-5p/SOCS3/STAT3 signaling pathway that contributes to viral replication and IL-6 production in RABV-infected cells, with PGG exerting its antiviral effect by inhibiting the production of miR-455-5p and the activation of STAT3. [ABSTRACT FROM AUTHOR]

Abstract Penta-O-galloyl-β- d -glucose (PGG) was purified and identified from Radix Paeoniae Alba by HSCCC and HPLC/ESI-MS, and its inhibitory effects on adipogenesis and TNF-α-induced inflammation were assessed in 3T3-L1 cell line. The results showed that PGG dose-dependently reduced intracellular lipids accumulation, and this involved decrease the expression levels of major adipogenic markers, PPARγ, C/EBP α, through MAPKs inhibition. This was accompanied by a reduction of lipogenic genes, ACC, FAS, and SCD-1, involved in fatty acid synthesis. Furthermore, PGG also inhibited TNF-α-induced expression of inflammatory cytokines including IL-6 and MCP-1 in the matured 3T3-L1 adipocytes. The inhibitions were likely mediated by blocking the MAPKs and NF-κB activation. These findings highlighted that PGG could serve as a potent therapeutic agent for controlling obesity and obesity-related chronic inflammation. Graphical abstract Image 1 Highlights • An efficient method for preparing PGG from Radix Paeoniae Alba by HSCCC in a single step was established for the first time. • PGG could greatly inhibit adipogenesis of 3T3-L1 cells through MAPK signaling pathway. • PGG could attenuate TNF-α-mediated adipocyte inflammation possibly through the MAPKs, and NF-κB pathways. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Self-assembly of PDMS-E grafted gelatin (PGG) is investigated in suit. • CLSM, CD, HR-TEM and XPS reveal the structure evolution of PGG at a molecular level. • Programmed self-assembly of PGG offers a superhydrophobic coating on porcine skin. • A new mechanism is proposed for developing potential application in biomaterials. Abstract Understanding the assembly mechanisms of supramolecular architectures in nature is essential for the design and synthesis of novel biomaterials. In the work, self-assembly of gelatin-mono epoxy terminated polydimethylsiloxane polymer (PGG) controlled by electrostatic and hydrophobic interactions between gelatin and sodium dodecyl sulfate (SDS) was investigated in suit. Confocal laser scanning microscopy, circular dichroism spectroscopy, high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy were conducted to reveal the structure evolution of PGG at a molecular level with the increment of SDS concentration, including micro-sized sphere, core-shell and multi-layer structure. Notably, the multi-layer structure was formed from the large contribution of antiparallel β -sheets on the boundary and new hydrophobic aggregation driven by higher monomer conversions. The delicate supramolecular architectures preliminarily present excellent anti-water, anti-contamination and anti-radiation properties in the surface of skin. The excellent self-cleaning function of PGG indicates potential application in biomaterials. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) still remains an incurable disease, therefore discovery of novel drugs boosts the therapeutics for MM. The natural compound 1,2,3,4,6-Penta-O-galloyl-beta-D-glucopyranoside (PGG) has been shown to exhibit antitumor activities against various cancer cells. Here, we aim to evaluate antitumor effects of PGG on MM cell lines. PGG inhibited the growth of three different MM cell lines in a dose- and time-dependent manner. Cell cycle analysis revealed that PGG treatment caused cell cycle arrest in G1 phase. It also induced apoptosis which was indicated by significant increases of Annexin V positive cells, caspase 3/7 activity, and cleaved caspase 3 expression in PGG treated MM cell. Since MYC is frequently hyperactivated in MM and inhibition of MYC leads to MM cell death. We further demonstrated that PGG decreased MYC expression in protein and mRNA levels and reversed the mRNA expression of MYC target genes such as p21, p27, and cyclin D2. In addition, PGG also reduced protein expression of DEPTOR which is commonly overexpressed in MM. Unexpectedly, PGG antagonized the cytotoxic effect of bortezomib in the combination treatment. However, PGG treatment sensitized MM cells to another proteasome inhibitor MG132 induced cytotoxicity. Moreover, MYC inhibitor JQ1 enhanced the cytotoxic effect of bortezomib on MM cells. Our findings raised concerns about the combinatory use of bortezomib with particular types of chemicals. The evidence also provide useful insights into the combination of MYC and proteasome-inhibitors for MM therapy. Finally, PGG has a therapeutic potential for treatment of MM and further development is mandatory.

Multiple myeloma (MM) still remains an incurable disease, therefore discovery of novel drugs boosts the therapeutics for MM. The natural compound 1,2,3,4,6-Penta-Ogalloyl- beta-D-glucopyranoside (PGG) has been shown to exhibit antitumor activities against various cancer cells. Here, we aim to evaluate antitumor effects of PGG on MM cell lines. PGG inhibited the growth of three different MM cell lines in a dose- and time-dependent manner. Cell cycle analysis revealed that PGG treatment caused cell cycle arrest in G1 phase. It also induced apoptosis which was indicated by significant increases of Annexin V positive cells, caspase 3/7 activity, and cleaved caspase 3 expression in PGG treated MM cell. Since MYC is frequently hyperactivated in MM and inhibition of MYC leads to MM cell death. We further demonstrated that PGG decreased MYC expression in protein and mRNA levels and reversed the mRNA expression of MYC target genes such as p21, p27, and cyclin D2. In addition, PGG also reduced protein expression of DEPTOR which is commonly overexpressed in MM. Unexpectedly, PGG antagonized the cytotoxic effect of bortezomib in the combination treatment. However, PGG treatment sensitized MM cells to another proteasome inhibitor MG132 induced cytotoxicity. Moreover, MYC inhibitor JQ1 enhanced the cytotoxic effect of bortezomib on MM cells. Our findings raised concerns about the combinatory use of bortezomib with particular types of chemicals. The evidence also provide useful insights into the combination of MYC and proteasome-inhibitors for MM therapy. Finally, PGG has a therapeutic potential for treatment of MM and further development is mandatory. [ABSTRACT FROM AUTHOR]

The compound 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), a gallotannin present in various plants such as Rhus chinensis Mill and Paeonia suffruticosa, has a broad spectrum of antiviral effects. The present study investigated its potency against infection of mice with rabies virus (RABV). Results demonstrated that PGG strongly inhibited virus titers (50-fold), viral mRNA expression (up to 90%), and protein synthesis in vitro. Importantly, we found that PGG not only suppressed viral adsorption and entry, but also directly inactivated RABV through suppression of autophagy by mediating activation of the mTOR-dependent autophagy signaling pathway. In vivo, PGG (10 mg/kg) alleviated the clinical symptoms and reduced the mortality of infected mice by 27.3%. Collectively, our results indicate that PGG has potent anti-RABV effect, and merits further investigation as an anti-RABV drug.

Background: Drug resistance is one of the bottlenecks of cancer chemotherapy in the clinic. Polymeric nanomedicine is one of the most promising strategies for overcoming poor chemotherapy responses due to the multidrug resistance (MDR). Methods: In this study, a new polymer-based drug delivery system, poly(Lγ-glutamylglutamine)-doxorubicin (PGG-Dox) conjugate, was studied in both drug-induced resistant human breast cancer MDA-MB-231/MDR cells and their parent human breast cancer MDA-MB-231 cells. The effect of PGG on facilitating the growth inhibition of Dox against multidrug resistant cells were investigated by evaluating the cytotoxicity of PGG-Dox conjugate, PGG/Dox unconjugated complex and free Dox on both cells. The underlying mechanisms in resistant cells were further studied via the intracellular traffic studies. Results: Both conjugated and unconjugated PGG significantly increased Dox uptake, prolonged Dox retention and reduced Dox efflux in the MDA-MB-231/MDR cells. The PGG-Dox conjugate is taken up by tumor cells mainly by pinocytosis pathway, in which PGG-Dox conjugate-containing vesicles are formed and enter the cells. Conclusions: This study indicated that both polymer-drug conjugate and unconjugated complex are promising strategies of overcoming resistance of anti-tumor drugs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Mechanisms of the very early steps of Aβ 1-42 protofibril disassembly by PGG were studied. • The probability of β-sheet structure in Aβ 1-42 protofibril was reduced by PGG. • PGG weakened the interactions between Chain-1 and Chain-2 in Aβ 1-42 protofibril. • PGG markedly disrupted the Lys 28 -Ala 42 salt bridges network in Aβ 1-42 protofibril. Aβ peptide aggregates were the main targets to treat AD. Previous experimental study demonstrated that the 1, 2, 3, 4, 6-penta- O -galloyl-β-D-glucopyranose (PGG, containing 5 gallate moieties) dramatically destabilized the preformed Aβ fibril in vitro and in vivo. However, the mechanisms were still poorly understood. Herein, by performing molecular dynamics simulations, the detailed mechanisms of the very early steps of Aβ 1-42 pentameric protofibril disassembly by PGG were explored. It was demonstrated that the binding of PGG molecules to Aβ 1-42 pentameric protofibril disrupted the β-sheet structure, weakened the interactions between Chain-1 and Chain-2, and disturbed the Lys 28 -Ala 42 salt bridges in Aβ 1-42 pentameric protofibril. We found that the hydrophobic interactions, hydrogen bonds, pi-pi interactions and cation-pi interactions existed between PGG molecules and amino acid residues in the corner of L-shaped part (Phe 4 -Leu 17) were conducive to the disaggregation of the close interactions between Chain-1 and Chain-2. Moreover, PGG molecules disrupted the Lys 28 -Ala 42 salt bridges not only by the hydrogen bonds and cation-pi interactions with Lys 28 but also through the interactions with C-terminal hydrophobic amino acid residues. We believed that our results could provide significant insights into the mechanisms of the very early steps of Aβ 1-42 pentameric protofibril disassembly by PGG. [ABSTRACT FROM AUTHOR]

Abstract: Astringency is an organoleptic property resulting mostly from the interaction of salivary proteins with dietary polyphenols. It is of great importance to consumers but being typically measured by sensorial panels it turns out subjective and expensive. The main goal of the present work is to develop a sensory system to estimate astringency relying on protein/polyphenol interactions. For this purpose, a model protein was immobilized on a sensory gold surface and its subsequent interaction with polyphenols was measured by Surface Plasma Resonance (SPR). α-amylase and pentagalloyl glucose (PGG) were selected as model protein and polyphenol, respectively. To ensure specific binding between these, various surface chemistries were tested. Carboxylic terminated thiol decreased the binding ability of PGG and allowed covalent attachment of α-amylase to the surface. The pH 5 was the optimal condition for α-amylase immobilization on the surface. Further studies focus on Localized SPR sensor and application to wine samples, providing objectivity when compared to a trained panel. [Copyright &y& Elsevier]

• HFD consumption alteres the expression of genes involved in lipid metabolism. • PGG reduces HFD-mediated body weight gain and hepatic steatosis. • PGG reverses HDF-induced alterations in hepatic lipid metabolic gene expression. • PGG, a well tolerated natural product, holds the potential for NAFLD treatment. Non-alcoholic fatty liver disease (NAFLD) is currently the most frequently occurring liver disorder in the world. However, a specific drug for the treatment of patients with NAFLD is not available. Therefore, the discovery of novel compounds for the treatment of NAFLD and elucidation of the underlying mechanisms of therapeutic drugs that can be used to treat this disease are urgently needed. 1,2,3,4,6 penta- O -galloyl-β- d -glucose (PGG) is known to exert anti-inflammatory, antidiabetic, and hepatoprotective effects. However, little is known about the therapeutic potential of PGG in NAFLD. In this study, we investigated the effects of PGG on a high-fat diet (HFD)-induced mouse model of NAFLD. PGG was co-administered along with an HFD to C57BL/6 mice. After eight weeks of treatment, serum biochemistry, liver steatosis, and lipid metabolism-related genes were examined. The results showed that PGG treatment significantly reduced HFD-induced gain in body weight, liver steatosis, and leukocyte infiltration in a dose-dependent manner. Furthermore, PGG treatment markedly reduced serum triglyceride and glucose levels in HFD mice. Moreover, alterations in the mRNA expression of genes involved in lipid metabolism, including Hmgcr , Acc1 , Abca1 , Mttp , and Cd36 , observed in the livers of HFD-treated mice were significantly reversed by PGG treatment. PGG significantly reduced HFD-induced protein expression of CD36, which is associated with fatty acid uptake, insulin resistance, hyperinsulinemia, and increased hepatic steatosis, in the liver of HFD mice. These results suggest that PGG inhibits HFD-induced hepatic steatosis and reverses HFD-induced alterations of gene expression in lipid metabolism. PGG has been shown to be well tolerated; therefore, it has potential uses in NAFLD treatment. [ABSTRACT FROM AUTHOR]

The compound 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), a gallotannin present in various plants such as Rhus chinensis Mill and Paeonia suffruticosa, has a broad spectrum of antiviral effects. The present study investigated its potency against infection of mice with rabies virus (RABV). Results demonstrated that PGG strongly inhibited virus titers (50-fold), viral mRNA expression (up to 90%), and protein synthesis in vitro. Importantly, we found that PGG not only suppressed viral adsorption and entry, but also directly inactivated RABV through suppression of autophagy by mediating activation of the mTOR-dependent autophagy signaling pathway. In vivo, PGG (10 mg/kg) alleviated the clinical symptoms and reduced the mortality of infected mice by 27.3%. Collectively, our results indicate that PGG has potent anti-RABV effect, and merits further investigation as an anti-RABV drug. [ABSTRACT FROM AUTHOR]

Growing evidence has demonstrated that autophagy plays important and paradoxical roles in carcinogenesis, while senescence is considered to be a crucial tumor-suppressor mechanism in cancer prevention and treatment. In the present study we demonstrated that both autophagy and senescence were induced in response to penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG), a chemopreventive polyphonolic compound, in multiple types of cancer cells. Analysis of these 2 events over the experimental time course indicated that autophagy and senescence occurred in parallel early in the process and dissociated later. The long-term culture study suggested that a subpopulation of senescent cells may have the capacity to reenter the cell cycle. Inhibition of autophagy by either a chemical inhibitor or RNA interference led to a significant reduction of PGG-induced senescence, followed by induction of apoptosis. These results suggested that autophagy promoted senescence induction by PGG and that PGG might exert its anticancer activity through autophagy-mediated senescence. For the first time, these findings uncovered the relationships among autophagy, senescence, and apoptosis induced by PGG. In addition, we identified that unfolded protein response signaling played a pivotal role in the autophagy-mediated senescence phenotype. Furthermore, our data showed that activation of MAPK8/9/10 (mitogen-activated protein kinase 8/9/10/c-Jun N-terminal kinases) was an essential upstream signal for PGG-induced autophagy. Finally, the key in vitro results were validated in vivo in a xenograft mouse model of human HepG2 liver cancer. Our findings provided novel insights into understanding the mechanisms and functions of PGG-induced autophagy and senescence in human cancer cells.