SARM1 participates in axonal degeneration and mitochondrial dysfunction in prion disease.

Prion disease represents a group of fatal neurogenerative diseases in humans and animals that are associated with energy loss, axonal degeneration, and mitochondrial dysfunction. Axonal degeneration is an early hallmark of neurodegeneration and is triggered by SARM1. We found that depletion or dysfunctional mutation of SARM1 protected against NAD+ loss, axonal degeneration, and mitochondrial functional disorder induced by the neurotoxic peptide PrP106-126. NAD+ supplementation rescued prion-triggered axonal degeneration and mitochondrial dysfunction and SARM1 overexpression suppressed this protective effect. NAD+ supplementation in PrP106-126-incubated N2a cells, SARM1 depletion, and SARM1 dysfunctional mutation each blocked neuronal apoptosis and increased cell survival. Our results indicate that the axonal degeneration and mitochondrial dysfunction triggered by PrP106-126 are partially dependent on SARM1 NADase activity. This pathway has potential as a therapeutic target in the early stages of prion disease.

ONS resolution prediction based on Rasch model.

IoT (Internet of Things) involves a wide range of fields, and its application scenarios are complex and diverse. Failure of security defense in any link of IoT may lead to huge information leakage and immeasurable losses. IoT security problem is affecting and restricting its application prospect, and has become one of the hotspots in the field of IoT. ONS (Object Naming Service) is responsible for mapping function from EPC code information to URI (Uniform Resource Identifier). The security mechanism of ONS has been extensively studied by more and more scholars in recent years. The purpose of this paper is to apply Rasch, a famous psychological model, to ONS resolution security technology. Through observing the past resolution result, the ability of ONS resolution and the difficulty of EPC code can be calculated. With the difference between the ability of ONS resolution and the difficulty of EPC code, this model can predict the probability of the ONS future resolution to achieve the purpose of privacy protection in IoT addressing. Through simulation and Ministep software, the feasibility of the model is verified.

Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition.

PURPOSE: Jatrorrhizine (JAT) is a natural protoberberine alkaloid, possesses detoxification, bactericidal and hypoglycemic activities. However, its anti-cancer mechanism is not clear. This study aimed to investigate the mechanism of JAT through which inhibits colorectal cancer in HCT-116 and HT-29 cells. METHODS: MTT assay and colony formation assay were used to check the cell proliferation ability. Cell apoptosis and cell cycle were measured by Hoechst 33342 staining and flow cytometry, respectively. Cell migration and invasion were detected by scratch wound healing assay and trans-well assay, respectively. Further, expression of related proteins was examined via Western blotting and the in vivo anti-cancer effect of JAT was confirmed by nude mice xenograft model. RESULTS: The research showed that JAT inhibited the proliferation of HCT-116 and HT-29 cells with IC50 values of 6.75±0.29 µM and 5.29±0.13 µM, respectively, for 72 hrs. It has also showed a time dependently, cell cycle arrested in S phase, promoted cell apoptosis and suppressed cell migration and invasion. In addition, JAT inhibited Wnt signaling pathway by reducing ß-catenin and increasing GSK-3ß expressions. Increased expression of E-cadherin, while decreased N-cadherin, indicating that JAT treatment suppressed the process of cell epithelial-mesenchymal transition (EMT). In HCT-116 nude mice xenograft model, JAT inhibited tumor growth and metastasis, and induced apoptosis of tumor cells. CONCLUSION: This study demonstrated that JAT efficiently inhibited colorectal cancer cells growth and metastasis, which provides a new point for clinical treatment of colorectal cancer.

[Analysis on medication rules of modern traditional Chinese medicines in treating palpitations based on traditional Chinese medicine inheritance support system].

To analyze the prescription and medication rules of Chinese medicines in the treatment of palpitations in the Chinese journal full text database(CNKI) by using traditional Chinese medicine inheritance system, and provide a reference for further research and development of modern traditional Chinese medicines(TCMs) in treatment of palpitations. In order to give better guidance for clinical mediation, prescriptions used for treatment of palpitations in CNKI were collected, and then were input to the TCM inheritance support system for establishing a Chinese medicine prescription database for palpitations. The software's revised mutual information, complex system entropy clustering and other data mining methods were adopted to analyze the prescriptions according to the frequencies of herbs, "four natures", "five flavors" and "meridians" of the high-frequency medicines in the database, identify the core herbs and application characteristics, and analyze the prescription rules and medication experience. Totally, 545 prescriptions used for palpitation were included in this study and involved 247 Chinese herbs. The analysis results showed that the herbs in prescriptions for palpitation mostly had the warm property, and the herbs in heart and spleen meridian accounted for a larger proportion, indicating that the treatment was mainly to nourish heart and strengthen spleen. The top 11 herbs in usage frequency were consistent with the high-frequency medicines in medication patterns of common herbal pairs; therefore, we considered that these 11 herbs were the core herbs; the core herbal combination included Cassia Twig, Licorice, fossil fragments, Ostreae decoction, and evolved into 9 new prescriptions for treating palpitation. Our results objectively presented the prescription and medication rules for treating palpitation and provided extremely effective guidance for the clinical therapy.

[Effect of IL-1ß on inflammatory factors synthesis of human gingival fibroblasts attached to different titaniums].

PURPOSE: To evaluate the effects of IL-1ß on inflammatory factors synthesis of human gingival fibroblasts on different surfaces of titaniums in vitro. METHODS: Human gingival fibroblasts were cultured on 3 different kinds of titaniums. The cells were stimulated with IL-1ß, and the IL-6 and IL-8 production was detected by polymerase chain reaction (PCR) after 3, 6 and 24 h. The date was statistically analyzed with SPSS13.0 software package. RESULTS: A significant increase of the expression of gingival fibroblasts to inflammatory factors (IL-6, IL-8) after IL-1ß was noted; PCR results of the production of inflammatory factors in gingival fibroblasts with the intervention of IL-1ß showed that the production of inflammatory factors (IL-6, IL-8) on titanium and titanium alloy were less than that on the titanium nitride. CONCLUSIONS: IL-1ß can stimulate high expression of inflammatory factors; The production of IL-6 and IL-8 on titanium and titanium alloy are less, suggesting that implant made of titanium and titanium alloy can reduce the incidence of peri-implant inflammation, and improve the successful rate of implantation.

SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo.

Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent.