Protective Effects of Salvia miltiorrhizae on Multiple Organs of Rats with Obstructive Jaundice

Purpose. we aim to explore the protective effects of Salvia miltiorrhizae injection on multiple organs of obstructive jaundice (OJ) rats through observing the impact of this injection on the pathological alterations in these organs and the contents of endotoxin, PLA2, and TNF-α in the blood. Methods. A total of 90 mice were randomly divided into sham-operated group, model-control group, and Salvia miltiorrhizae-treated group (n = 30). According to the duration of postoperative administration, each group was further divided into two subgroups, namely, 21 d subgroup (consecutive administration for 21 d, n = 15) and 28 d subgroup (consecutive administration for 28 d, n = 15). After administration, the pathological alterations in multiple organs were observed and the contents of endotoxin, PLA2, and TNF-α in the blood were determined. Results. Compared to model control group, the number of dead rats in treated group decreased though there was no statistical difference between the two groups. The pathological alterations in the liver, kidney, and spleen in treated group showed varying degrees of mitigation. At all time points, the contents of plasma endotoxin declined significantly. On day 28, plasma PLA2 content in treated group was significantly lower than that in model-control group. Conclusion. Salvia miltiorrhizae injection is able to obviously reduce the contents of inflammatory mediators in the blood of OJ rats and exert some protective effects on multiple organs of these rats

Study on the Rough-set-based Clustering Algorithm for Sensor Networks

The traditional clustering algorithm is a very typical level routing algorithm in wireless sensor networks (WSN). On the basis of the classical LEACH (Low Energy Adaptive Clustering Hierarchy) algorithm, this paper proposes an energy efficient clustering algorithm in WSN. Through the introduction of rough set, the new algorithm mainly introduces how to confirm an optimized strategy to choose the cluster head effectively by the simplified decision table. That is to say, by discrete normalized data preprocessing of attribute value, getting discretization decision table. Finally, the results from simulated experiments show that the clustering algorithm based on rough set theory can optimize the clustering algorithm in network data. That is to say, the rough-set-based clustering algorithm can effectively choose the cluster head, balance the energy of the nodes in the cluster and prolong the lifetime of sensor networks

New Approach to Develop Ultra-High Inhibitory Drug Using the Power Function of the Stoichiometry of the Targeted Nanomachine or Biocomplex

AIMS: To find methods for potent drug development by targeting to biocomplex with high copy number. METHODS: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui\u27s Triangle [Formula: see text], where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population. RESULTS: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals q(z), demonstrating the multiplicative effect of stoichiometry on inhibition with stoichiometry 1000 \u3e 6 \u3e 1. Complete inhibition of virus replication was found when Z = 6. CONCLUSION: Drug inhibition potency depends on the stoichiometry of the targeted components of the biocomplex or nanomachine. The inhibition effect follows a power function of the stoichiometry of the target biocomplex

Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model

<p>Abstract</p> <p>Background</p> <p>Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model.</p> <p>Results</p> <p>Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord.</p> <p>Conclusions</p> <p>These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain.</p

Security Proof of JAMBU under Nonce Respecting and Nonce Misuse Cases

JAMBU is an AEAD mode of operation which entered the third round of CAESAR competition. However, it does not have a security proof like other modes of operation do, and there was a cryptanalysis result that has overthrown the security claim under nonce misuse case by the designers. In this paper, we complement the shortage of the scheme by giving security proofs of JAMBU both under nonce respecting case and nonce misuse case. We prove that JAMBU under nonce respecting case has a slightly lower security than the birthday bound of $n$ bits, and JAMBU under nonce misuse case has a tight security bound of $n/2$ bits

VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU

Cell cycle checkpoint kinases play a pivotal role in protecting against replicative stress. In this study, valproic acid (VPA), a histone deacetylase inhibitor (HDACi), was found to promote breast cancer MCF-7 cells to traverse into G2/M phase for catastrophic injury by promoting PPP2R2A (the B-regulatory subunit of Phosphatase PP2A) to facilitate the dephosphorylation of Chk1 at Ser317 and Ser345. By contrast, VPA protected normal 16HBE cells from HU toxicity through decreasing PPP2R2A expression and increasing Chk1 phosphorylation. The effect of VPA on PPP2R2A was at the post-transcription level through HDAC1/2. The in vitro results were affirmed in vivo. Patients with lower PPP2R2A expression and higher pChk1 expression showed significantly worse survival. PPP2R2A D197 and N181 are essential for PPP2R2A-Chk1 signaling and VPA-mediated bidirectional effect on augmenting HU-induced tumor cell death and protecting normal cells

Inhibition of Glucose-6-Phosphate Dehydrogenase Could Enhance 1,4-Benzoquinone-Induced Oxidative Damage in K562 Cells

Benzene is a chemical contaminant widespread in industrial and living environments. The oxidative metabolites of benzene induce toxicity involving oxidative damage. Protecting cells and cell membranes from oxidative damage, glucose-6-phosphate dehydrogenase (G6PD) maintains the reduced state of glutathione (GSH). This study aims to investigate whether the downregulation of G6PD in K562 cell line can influence the oxidative toxicity induced by 1,4-benzoquinone (BQ). G6PD was inhibited in K562 cell line transfected with the specific siRNA of G6PD gene. An empty vector was transfected in the control group. Results revealed that G6PD was significantly upregulated in the control cells and in the cells with inhibited G6PD after they were exposed to BQ. The NADPH/NADP and GSH/GSSG ratio were significantly lower in the cells with inhibited G6PD than in the control cells at the same BQ concentration. The relative reactive oxygen species (ROS) level and DNA oxidative damage were significantly increased in the cell line with inhibited G6PD. The apoptotic rate and G2 phase arrest were also significantly higher in the cells with inhibited G6PD and exposed to BQ than in the control cells. Our results suggested that G6PD inhibition could reduce GSH activity and alleviate oxidative damage. G6PD deficiency is also a possible susceptible risk factor of benzene exposure

Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages

Polycyclic aromatic hydrocarbons (PAHs) are common persistent organic pollutants that are carcinogenic, teratogenic and mutagenic, causing a variety of harm to human health. In this study, we investigated the mechanism of how valproic acid (VPA) interferes with the carcinogenesis of PAHs protect normal tissues via the regulation of macrophages’ function. Using the established model of transformed malignant breast cancer by 7,12-dimethylbenz[a]anthracene (DMBA), a representative PAH carcinogen, we discovered VPA induces the polarization of macrophages toward the M1 phenotype in the tumor tissues, facilitates the expression of pro inflammatory cytokines such as IFN-γ, IL-12 and TNF-α, activates CD8+ T cells to secret Granzyme B thus to promote the apoptosis of tumor cells and suppresses the viability of vascular endothelial cells in tissue stroma of tumor. Surprisingly, VPA selectively induces macrophages to polarize towards the M2 phenotype in normal tissues and promotes the expression of anti-inflammatory cytokines such as IL-10 to enhance cell proliferation. Additionally, at the cellular level, VPA can directly regulate the polarization of macrophages to affect the growth of vascular endothelial cells by simulating the living conditions of tumor and normal cells. Collectively, VPA exerts an interventional effect on tumor growth and a protective effect on normal tissues by regulation of selective macrophages’ polarization in their microenvironment