Fixed-Time Synchronization of Coupled Oscillator Networks with a Pacemaker.

This paper investigates the fixed-time synchronization problem of a Kuramoto-oscillator network in the presence of a pacemaker. Based on the framework of the cyber-physical system (CPS), fixed-time synchronization criteria of such network are presented respectively for identical and non-identical oscillators. In virtue of Lyapunov stability analyses, sufficient conditions are deduced for achieving phase agreement and frequency synchronization for arbitrary initial phases and/or frequencies under distributed control strategies. Theoretical analysis shows that synchronization can be achieved in a fixed time, which is unrelated to initial phases/frequencies. Furthermore, the upper bounds of synchronization time are also obtained. Finally, the numerical simulations also verify the effectiveness of the derived results.

Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in triple-negative breast cancer cells.

Although tetraarsenic hexoxide is known to exert an anti-tumor effect by inducing apoptosis in various cancer cells, its effect on other forms of regulated cell death remains unclear. Here, we show that tetraarsenic hexoxide induces the pyroptotic cell death through activation of mitochondrial reactive oxygen species (ROS)-mediated caspase-3/gasdermin E (GSDME) pathway, thereby suppressing tumor growth and metastasis of triple-negative breast cancer (TNBC) cells. Interestingly, tetraarsenic hexoxide-treated TNBC cells exhibited specific pyroptotic characteristics, including cell swelling, balloon-like bubbling, and LDH releases through pore formation in the plasma membrane, eventually suppressing tumor formation and lung metastasis of TNBC cells. Mechanistically, tetraarsenic hexoxide markedly enhanced the production of mitochondrial ROS by inhibiting phosphorylation of mitochondrial STAT3, subsequently inducing caspase-3-dependent cleavage of GSDME, which consequently promoted pyroptotic cell death in TNBC cells. Collectively, our findings highlight tetraarsenic hexoxide-induced pyroptosis as a new therapeutic strategy that may inhibit cancer progression of TNBC cells.

Effect of weimaining on apoptosis and Caspase-3 expression in a breast cancer mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Weimaining (WMN) is a condensed Tannin compound extracted from Fagopyrum cymosum (Trevir.) Meisn., which comes from the roots of buckwheat, a type of Chinese herbal medicine, was first recorded in "Bencao Shiyi". WMN has inhibitory effects on multiple cancer types and is widely used in clinical practice; however, the mechanism underlying the anti-tumor effect of WMN is still unclear. AIM OF THE STUDY: To investigate the effect of WMN on the cellular activity and apoptosis of mouse breast cancer 4T1-luc2 cells, and caspase-3 and cleaved-caspase-3 expression. MATERIALS AND METHODS: Luciferase-labeled mouse breast cancer 4T1-luc2 cells were inoculated into the mouse breast pad to establish a luciferase-labeled mouse breast cancer cell model. BALB/C-nu mice were randomly divided into model, WMN, and low-molecular-weight heparin (LMWH) groups (n = 10). Another 10 mice served as the normal control group (no cancer cell injection). The WMN group was administered WMN 250 mg/kg per day for 14 days, the LMWH group was given LMWH (1500 U/kg) daily for 14 days by intraperitoneal injection, and the model and normal control groups were given an equal dose of 0.9% NaCl. The number and distribution of transplanted tumors in 4T1-luc2 breast cancer cells were observed in nude mice by an in vivo imaging system at the time of inoculation after successful modeling, and on days 7 and 14 after drug administration. Tumor cell apoptosis was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method; caspase-3 mRNA expression was detected by RT-PCR and Western blotting was applied to detect the levels of caspase-3 and cleaved-caspase-3 protein expression. RESULTS: The apoptosis index (AI) of the WMN group was detected by the TUNEL method, and the AI increased with the increase of treatment time. Compared with the model group, the mRNA expression of caspase-3 and the protein levels of caspase-3 and cleaved-caspase-3 were notably elevated in the WMN group. After in vivo bioluminescent imaging, the total photon number of the WMN group was found to be lower than that of the LWMH group on day 14 after administration. Additionally, the AI and expression levels of caspase-3 mRNA, caspase-3, and cleaved-caspase-3 protein of the WMN group were higher than those of the LWMH group. CONCLUSION: WMN can effectively suppress the growth of 4T1-luc2 breast cancer xenografts in mice, and promote the apoptosis of breast cancer cells by upregulating the expression of caspase-3.

Anti-Cancer Activity of As4O6 and its Efficacy in a Series of Patient-Derived Xenografts for Human Cervical Cancer.

PURPOSE: To investigate the anti-cancer effects of tetraarsenic hexoxide (TAO, As4O6) in cervical cancer cell lines and in a series of patient-derived xenograft (PDX) mouse models. METHODS: Human cervical cancer cell lines, including HeLa, SiHa and CaSki, and human umbilical vein endothelial cells (HUVECs), were used to evaluate the anti-cancer activity of TAO. Cellular proliferation, apoptosis, and enzyme-linked immunosorbent assay (ELISA) for matrix metallopeptidase 2 (MMP-2) and 9 (MMP-9) were assessed. The tumor weights of the PDXs that were given TAO were measured. The PDXs included primary squamous cell carcinoma, primary adenocarcinoma, recurrent squamous cell carcinoma, and recurrent adenocarcinoma. RESULTS: TAO significantly decreased cellular proliferation and increased apoptosis in cervical cancer cell lines and HUVEC. The functional studies on the cytotoxicity of TAO revealed that it inhibited the activation of Akt and vascular endothelial growth factor receptor 2 (VEGFR2). It also decreased the concentrations of MMP-2 in both cervical cancer cell lines and HUVECs. Active caspase-3 and p62 were both increased by the treatment of TAO, indicating increased rates of apoptosis and decreased rates of autophagy, respectively. In vivo studies with PDXs revealed that TAO significantly decreased tumor weight for both primary squamous cell carcinoma and adenocarcinoma of the cervix. However, this anti-cancer effect was not seen in PDXs with recurrent cancers. Nevertheless, the combination of TAO with cisplatin significantly decreased tumor weight in PDX models for both primary and recurrent cancers. CONCLUSIONS: TAO exerted inhibitory effects on angiogenesis, cellular migration, and autophagy, and it showed stimulatory effects on apoptosis. Overall, it demonstrated anti-cancer effects in animal models for human cervical cancer.

Niu-Huang-Shen suppresses hepatocellular carcinoma cell growth and metastasis by regulating Yap1 expression.

Hepatocellular carcinoma (HCC) is one of the most common cancers types. Niu-Huang-Shen (NHS), a Chinese medicine, has been reported to exert antipyretic, anti-inflammatory and vasodilatation effects. However, whether NHS has inhibitory effects on HCC cell phenotypes has remained elusive. In the present study, Cell Counting Kit-8, colony formation, fluorescence-activated cell sorting and Transwell assays were used to evaluate the effect of NHS on cell proliferation, migration and invasion. The results indicated that NHS suppressed cell proliferation and invasion, inhibited cell apoptosis, and induced cell cycle arrest. In addition, NHS significantly suppressed the mRNA and protein expression of Yes-associated protein (YAP). It was concluded that NHS downregulated YAP expression and inhibited the Hippo signaling pathway as well as HCC cell growth and invasion. NHS may be a novel potential therapeutic for HCC patients.

Neuroprotective effects of autophagy induced by rapamycin in rat acute spinal cord injury model.

BACKGROUND/AIMS: To explore the effects of rapamycin-induced autophagy on apoptosis in a rat model of acute spinal cord injury (SCI), and to explore the effect of rapamycin on apoptosis in primary spinal cord cell culture. METHODS: SCI was induced at T10 in female adult Sprague-Dawley rats. After injury was induced, the rats were injected with rapamycin and/or methylprednisolone and were sacrificed at various days after injury. Apoptosis and autophagy were examined with TUNEL staining and electron microscopy. Hind limb function was assessed by the Gale scale. RESULTS: The expression of the apoptosis-related protein caspase-3 did not significantly increase until 21 days following injury, while increases in LC3II and LC3I began 10 days after injury, but then declined. TUNEL staining and electron microscopy confirmed that following injury autophagy occurred before apoptosis, but by 14 days after the injury, the level of autophagy had decreased significantly while the level of apoptosis showed a continued increase. Following treatment with rapamycin, apoptosis was significantly higher than in the vehicle control group, but significantly lower than in the sham-operated group, showing a protective effect of rapamycin. Gale scale grades in rats treated with rapamycin were significantly higher compared with the vehicle control group, suggesting a functional effect of rapamycin-induced inhibition of apoptosis. CONCLUSIONS: The results indicate that rapamycin significantly improved the prognosis of acute SCI in rats by inhibiting cell apoptosis. Rapamycin might be useful as a therapeutic agent for acute SCI.

Synchronization of a network coupled with complex-variable chaotic systems.

In this paper, synchronization of a network coupled with complex-variable chaotic systems is investigated. Adaptive feedback control and intermittent control schemes are adopted for achieving adaptive synchronization and exponential synchronization, respectively. Several synchronization criteria are established. In these schemes, the outer coupling matrix is not necessarily assumed to be symmetric or irreducible. Further, for a class of networks with an irreducible and balanced outer coupling matrix, a pinning control scheme is adopted for achieving synchronization. Numerical simulations are demonstrated to verify the effectiveness of the theoretical results.

[Effects of multi-nutrients supplementation on the nutritional status and antioxidant capability of healthy adults].

OBJECTIVE: To determine whether daily multivitamins/minerals supplement can improve nutrient status, plasma, antioxidant enzymes activity and total antioxidant capacity in healthy adults. METHODS: One hundred and fifty-one healthy adults living in a normal lifestyle with a mean age of 28 (20 - 50) years were recruited from Guangzhou. The subjects were divided into the supplement group and the control ineral supplements. METHODS: One hundred and fifty-one healthy adults living in a normal lifestyle with a mean age of 28 (20 - 50) years were recruited from Guangzhou. The subjects were divided into the supplement group and the control group carefully matched with age and gender. Supplement pellets (consisted of multivitamins/minerals, including VitA, VitC, VitE,Ca, Zn, Fe, Se, etc.) and placebo pellets (consisted of only dextrin with the same color, shape and size as the supplement pellets) were administrated in a double-blinded manner for 8 week. The nutrients intake data of the research subjects were collected daily by a 24-hour dietary recall method. Blood samples were collected at the beginning and the end of the intervention period for determining the nutritional status, the activities of antioxidant enzymes and the products of oxidative damage. RESULTS: The dietary intake of nutrients was insufficient in these subjects. The levels of plasma VitC, alpha-tocopherol, beta-carotene, Zn, Fe and Se in the supplement group were increased in comparison with the control group by 46%, 28%, 116%, 7%, 30% and 28% respectively (P < 0.05), indicating that the nutritional status regarding antioxidant nutrients had largely been improved. But levels of plasma gamma-tocopherol were decreased by 25% in comparison with the control group (P < 0.05). The activities of GPX, CAT and T-AOC were increased in comparison with the control group and before the supplementation (P < 0.05), while the activities of SOD and the level of 8-isoprostanes remained steady. CONCLUSION: Supplementation of multiple micronutrients could effectively increase the levels of plasma VitC, alpha-tocopherol, beta-carotene, Zn, Fe and Se and the activities of GPX, CAT and T-AOC.

Adaptive synchronization and pinning control of colored networks.

A colored network model, corresponding to a colored graph in mathematics, is used for describing the complexity of some inter-connected physical systems. A colored network is consisted of colored nodes and edges. Colored nodes may have identical or nonidentical local dynamics. Colored edges between any pair of nodes denote not only the outer coupling topology but also the inner interactions. In this paper, first, synchronization of edge-colored networks is studied from adaptive control and pinning control approaches. Then, synchronization of general colored networks is considered. To achieve synchronization of a colored network to an arbitrarily given orbit, open-loop control, pinning control and adaptive coupling strength methods are proposed and tested, with some synchronization criteria derived. Finally, numerical examples are given to illustrate theoretical results.