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Resource-exchange-based incentive mechanisms are investigated for both selection cooperation (SC) and selection relaying (SR) networks using the cooperative bargaining game approach. Consider a user node that can act as a source as well as a potential relay for other nodes, and it is selfish to share an own resource with others only if the data rate achieved through cooperative relaying is not lower than that achieved without the cooperation by consuming the same amount of the resource. In the SC scenario, only one relay is allotted to a source. Then, a two-person SC game (SCG) is formulated to address the joint bandwidth and power allocation problem for two cooperative nodes. In the SR scenario, a set of relays is allotted to a source. Hence, we propose a one-to-many SR game (SRG) to address the multinode cooperation case. For both SCG and SRG, specific data frame structures are designed to accommodate both the bandwidth resource (in the form of transmission time) and the energy resource (in the form of transmission power) for a cooperative node. To achieve the system efficiency and per-node fairness objectives simultaneously, the Nash bargaining solution (NBS) method is used to solve both SCG and SRG. The existence and uniqueness of the NBS are proved. Moreover, theoretical analysis and simulations are provided to testify as to the effectiveness of the proposed SCG and SRG for efficient and fair resource allocation in the SC and SR scenarios, respectively. [ABSTRACT FROM PUBLISHER]

Disruption of the symbiosis of extra/intratumoral metabolism is a good strategy for treating tumors that shuttle resources from the tumor microenvironment. Here, we report a precision treatment strategy for enhancing pyruvic acid and intratumoral acidosis to destroy tumoral metabolic symbiosis to eliminate tumors; this approach is based on PEGylated gold and lactate oxidase-modified aminated dendritic mesoporous silica with lonidamine and ferrous sulfide loading (PEG-Au@DMSNs/FeS/LND@LOX). In the tumor microenvironment, LOX oxidizes lactic acid to produce pyruvate, which represses tumor cell proliferation by inhibiting histone gene expression and induces ferroptosis by partial histone monoubiquitination. In acidic tumor conditions, the nanoparticles release H 2 S gas and Fe 2+ ions, which can inhibit catalase activity to promote the Fenton reaction of Fe 2+ , resulting in massive ·OH production and ferroptosis via Fe 3+ . More interestingly, the combination of H 2 S and LND (a monocarboxylic acid transporter inhibitor) can cause intracellular acidosis by lactate, and protons overaccumulate in cells. Multiple intracellular acidosis is caused by lactate-pyruvate axis disorders. Moreover, H 2 S provides motive power to intensify the shuttling of nanoparticles in the tumor region. The findings confirm that this nanomedicine system can enable precise antitumor effects by disrupting extra/intratumoral metabolic symbiosis and inducing ferroptosis and represents a promising active drug delivery system candidate for tumor treatment.

As emerging nanosystems, nanomotors have been applied in the active treatment of many diseases. In this paper, Pt@chitosan-loaded melatonin asymmetrical nanomaterials embedded with L-serine (S, kidney injury molecule 1-targeting agent) were constructed to alleviate acute kidney injury (AKI). The Janus nanocarriers arrived at the renal injury site via the bloodstream and exhibited high permeability. Because of melatonin distribution in the kidneys combined with H 2 O 2 -stimulated O 2 release, the administration of the Janus nanosystem resulted in active treatment through the motion of nanomotors by asymmetrical O 2 release.

Patients with biliary tract cancer (BTC) were associated with poor prognosis and limited therapeutic options after first-line therapy currently. In this study, we sought to evaluate the feasibility and tolerability of sintilimab plus anlotinib as the second-line treatment for patients with advanced BTC. Eligible patients had histologically confirmed locally advanced unresectable or metastatic BTC and failed after the first-line treatment were recruited. The primary endpoint was overall survival (OS). Simultaneously, association between clinical outcomes and genomic profiling and gut microbiome were explored to identify the potential biomarkers for this regimen. Twenty patients were consecutively enrolled and received study therapy. The trail met its primary endpoint with a median OS of 12.3 months (95% CI: 10.1-14.5). Only four (20%) patients were observed of the grade 3 treatment-related adverse events (TRAEs) and no grade 4 or 5 TRAEs were detected. Mutation of AGO2 was correlated with a significantly longer OS. Abundance of Proteobacteria was associated with inferior clinical response. Therefore, sintilimab plus anlotinib demonstrated encouraging anti-tumor activity with a tolerable safety profile and deserved to be investigated in larger randomized trials for patients with advanced BTC subsequently., (© 2022 UICC.)

Background: Transient Ischemia/Reperfusion (I/R) is the main reason for brain injury and results in disruption of the Blood-Brain Barrier (BBB). It had been reported that BBB injury is one of the main risk factors for early death in patients with cerebral ischemia. Numerous investigations focus on the study of BBB injury which have been carried out., Objective: The objective of this study was to investigate the treatment function of the activation of the Hippo/Yes-Associated Protein (YAP) signaling pathway by combined Ischemic Preconditioning (IPC) and resveratrol (RES) before brain Ischemia/Reperfusion (BI/R) improves Blood-Brain Barrier (BBB) disruption in rats., Methods: Sprague-Dawley (SD) rats were pretreated with 20 mg/kg RES and IPC and then subjected to 2 h of ischemia and 22 h of reperfusion. The cerebral tissues were collected; the cerebral infarct volume was determined; the Evans Blue (EB) level, the brain Water Content (BWC), and apoptosis were assessed; and the expressions of YAP and TAZ were investigated in cerebral tissues., Results: Both IPC and RES preconditioning reduced the cerebral infarct size, improved BBB permeability, lessened apoptosis, and upregulated expressions of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) compared to the Ischemia/Reperfusion (I/R) group, while combined IPC and RES significantly enhanced this action., Conclusion: combined ischemic preconditioning and resveratrol improved blood-brain barrier breakdown via Hippo/YAP/TAZ signaling pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Aldehyde dehydrogenase-1 (ALDH1) has been shown to be a potential cancer stem cell marker in different types of cancer. However, the role of its expression in tumor cells and the microenvironment in different types of cancer is still controversial., Materials and Methods: ALDH1 protein was immunohistochemically investigated and analyzed in 157 samples of surgically dissected esophageal squamous cell carcinoma (ESCC) tissues., Results: ALDH1 protein expression in ESCC tumor cells was significantly associated with poor differentiation (p<0.05) and strongly positive ALDH1 expression in tumor cells was related with shorter overall survival (p<0.05), while the expression of ALDH1 in ESCC stromal cells had no significant relationship with clinicopathological features (p>0.05)., Conclusion: High expression of cancer stem cell marker ALDH1 in ESCC cells may thus portend a poor prognosis. However, its expression in the tumor microenvironment did not appear to have a role in ESCC behavior. More studies are warranted to find out the mechanisms to explain this., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aerobic glycolysis is one of the important hallmarks of cancer cells and eukaryotic cells. In this study, we have investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with UK5099 and the metabolic alteration as well as stemness phenotype of prostatic cancer cells. It was found that blocking pyruvate transportation into mitochondrial attenuated mitochondrial oxidative phosphorylation (OXPHOS) and increased glycolysis. The UK5099 treated cells showed significantly higher proportion of side population (SP) fraction and expressed higher levels of stemness markers Oct3/4 and Nanog. Chemosensitivity examinations revealed that the UK5099 treated cells became more resistant to chemotherapy compared to the non-treated cells. These results demonstrate probably an intimate connection between metabolic reprogram and stem-like phenotype of LnCap cells in vitro. We propose that MPC blocker (UK5099) application may be an ideal model for Warburg effect studies, since it attenuates mitochondrial OXPHOS and increases aerobic glycolysis, a phenomenon typically reflected in the Warburg effect. We conclude that impaired mitochondrial OXPHOS and upregulated glycolysis are related with stem-like phenotype shift in prostatic cancer cells.

Background: Aerobic glycolysis is an important hallmark of cancer cells. Deficiency of pyruvate dehydrogenase component α subunit (PDHE1α) leads to mitochondrial dysfunction and promotes glycolysis. Therefore, studies on the expression of PDHE1α in cancer are warranted., Patients and Methods: The PDHE1α protein was immunohistochemically investigated and analyzed in 157 samples of surgically dissected esophageal squamous cell carcinoma (ESCC) and 21 'normal' esophageal epithelia tissues., Results: PDHE1α protein expression was lower in ESCC. Absence of PDHE1α protein expression in tumor cells was found in 77.1% of cases. Negativity for PDHE1α protein in tumor cells was correlated with poor tumor differentiation (p<0.05) and shorter overall survival (p<0.05)., Conclusion: Lack of PDHE1α protein expression in ESCC is associated with poor prognosis. Our findings also verify the existence of aerobic glycolysis switch in ESCC, and strongly advocate novel therapeutic strategies in reversing the Warburg effect in tumors., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: A low quantity of mitochondrial DNA (mtDNA) is a risk factor in a variety of tumor types. However, it is unclear how mtDNA reduction influences tumor behavior., Material and Methods: mtDNA-deficient ovarian cancer cells were established by ethidium bromide (EtBr) treatment with additive combination of pyruvate and uridine., Results: The mtDNA-deficient cells had a low growth and colony-forming efficiency compared to the control cells. RNA sequencing revealed down-regulation of mitochondrion-related genes and up-regulation of genes related to cell proliferation and anti-apoptosis. The expression of genes involved in cancer metastasis, proliferation, angiogenesis, drug resistance and cancer cell stemness were also up-regulated. Intriguingly, cancer stem cell markers CD90 and CD117 were both up-regulated by EtBr dose-dependently in both cell lines., Conclusion: MtDNA deficiency may induce ovarian cancer stem cell-like properties through different ways in vitro, therefore contributing to different tumor behaviors., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)