// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Qian Zhu1, *, Guo-Liang Qiao2, *, Xiao-Chuan Zeng1, *, Yun Li1, Jian-Jun Yan3, Rui Duan1, Zhi-Yong Du4 1Department of General Surgery, Jingmen First People's Hospital, Jingmen 448000, Hubei Province, China 2Department of Medical Oncology, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Beijing, 100038, China 3First Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China 4Department of Hepatobiliary Surgery, Central Hospital of Wuhan, Wuhan 430014, Hubei Province, China *These authors have contributed equally to this work Correspondence to: Zhi-Yong Du, email: duzhiyong88@163.com Rui Duan, email: duanrui@sina.com Keywords: hepatocellular carcinoma, initiation factors, microarray, prognosis, tumor progression Received: October 07, 2015 Accepted: June 04, 2016 Published: June 22, 2016

Background: Alzheimer’s disease (AD) is the most common type of neurodegenerative disorder. There are few effective medications for halting the progression of AD. Telmisartan (TEL) is a widely used anti-hypertensive drug approved by FDA. Aside from treating hypertension, TEL has been revealed to provide protection against AD. However, the underlying mechanisms remain unclear. Objective: To investigate the mechanisms underlying the beneficial effects of TEL against AD. Methods: Eight-month-old APP/PS1 mice were administered with 5 mg/kg TEL once per day for 4 successive months. Nesting test, Y-maze test, and Morris water maze test were employed to assess the cognitive and executive functions. Neuronal and synaptic markers, amyloid-β (Aβ) pathology, neuroinflammation, and oxidative stress in the brains were measured. Specifically, components involved in Aβ production and degradation pathway were analyzed to explore the mechanisms underlying the therapeutic effect of TEL against Aβ pathology. The primary microglia were used to uncover the mechanisms underlying the anti-inflammatory effects of TEL in AD. Additionally, the preventive effect of TEL against AD were investigated using 4-month-old APP/PS1 mice. Results: TEL treatment ameliorated cognitive and executive impairments, neuronal and synaptic injury, Aβ pathology, neuroinflammation, and oxidative stress in APP/PS1 mice. The favorable effects of TEL on Aβ pathology were achieved by inhibiting enzymatic Aβ production and facilitating enzymatic and autophagic Aβ degradation. Meanwhile, the anti-inflammatory effects of TEL were accomplished via microglial PPARγ/NLRP3 pathway. The administration of TEL prior to symptom onset prevented AD-related cognitive decline and neuropathologies. Conclusion: TEL represents a promising agent for AD prevention and treatment.

Hepatocellular carcinoma (HCC) is one of the dominating tumors causing death due to lack of timely discovery and valid treatment. Abnormal increase of Rac GTPase activating protein 1 (RACGAP1) has been verified to be an oncogene in plenty tumors. The profound mechanism of RACGAP1 was rarely reported in HCC. In this study, we explored the function and mechanism of RACGAP1 in HCC through multiple analysis and experiments. RACGAP1 expression was up‐regulated in HCC samples and the high expression of RACGAP1 was an independent prognostic risk factor for HCC patients. Meanwhile, RACGAP1 promoted developments of HCC both in vitro and in vivo. We verified that RACGAP1 promoted proliferation of HCC via PI3K/AKT/CDK2 and PI3K/AKT/GSK3β/Cyclin D1 signaling pathway. RACGAP1 accelerated the invasion and metastasis of HCC via phosphorylation of GSK3β and nuclear translocation of β‐catenin. Furthermore, by luciferase reporter assay and Chromatin immunoprecipitation (ChIP) assay, we confirmed Recombinant GA Binding Protein Transcription Factor Alpha (GABPA) regulated the transcription of RACGAP1. All these findings revealed that RACGAP1 promotes the progression of HCC through a novel mechanism, which might be a new therapeutic target for HCC patients.

Diabetes osteoporosis (DOP) is a chronic bone metabolic disease induced by diabetes, whose morbidity continues to increase. Epimedium brevicornum Maxim (EB), a popular Chinese traditional medicine, has been used to treat bone diseases in China for thousands of years. But its material basis and specific mechanism of action are not clear. Epimedium brevicornum crude polysaccharide (EPE) is the main component, in this research the characterized the structure of EBPC1 purified from EPE was detected and its effects on cell proliferation, differentiation, and cytoskeletal in osteoblasts induced by high glucose. The molecular weight of EBPC1 was 10.5 kDa. It was mainly comprised of glucose and galactose, and the backbone of EBPC1 was→4)-α-D-Galp-(1→4)-α-D-Galp-(1→6)-β-D-Galp-(1→6)-β-D-Galp-(1→4)-α-D-Glcp-(1→4)-α-D-Glcp-(1→. The results from in vitro experiments revealed that EBPC1 significantly increased alkaline phosphatase (ALP) activity and mineralized nodule formation in primary osteoblasts, also significantly up-regulated expression of Alp mRNA and Runx2 mRNA in the presence of EBPC1 pretreatment. Moreover, EBPC1 modulated apoptosis via the regulation of Bax/Bcl2. These results indicate that EBPC1 treatment can promote osteogenesis during DOP, which can ameliorate apoptosis by regulating Bax/Bcl2 and accelerating osteogenesis in osteoblasts.

Staphylococcus aureus is an important causative pathogen of bloodstream infections. An amplification assay such as real-time PCR is a sensitive, specific technique to detect S. aureus. However, it needs well-trained personnel, and costs are high. A literature review focusing on rapid and simple methods for diagnosing S. aureus was performed. The following methods were included: (a) Hybrisep in situ hybridization test, (b) T2Dx system, (c) BinaxNow Staphylococcus aureus and PBP2a, (d) Gram staining, (e) PNA FISH and QuickFISH, (f) Accelerate Pheno^TM system, (g) MALDI-TOF MS, (h) BioFire FilmArray, (i) Xpert MRSA/SA. These rapid and simple methods can rapidly identify S. aureus in positive blood cultures or direct blood samples. Furthermore, BioFire FilmArray and Xpert MRSA/SA identify methicillin-resistant S. aureus (MRSA), and the Accelerate Pheno^TM system can also provide antimicrobial susceptibility testing (AST) results. The rapidity and simplicity of results generated by these methods have the potential to improve patient outcomes and aid in the prevention of the emergence and transmission of MRSA.

Conventional treatments for advanced endometriosis often have limited efficacy due to chemotherapy resistance, recurrence, and metastasis. This study analyzed clinical specimens to investigate the role of NXF1 in endometrial cancer (ECa) progression. Mouse models and molecular biology assays were used to elucidate NXF1’s function and mechanisms in vitro and in vivo. Results showed NXF1 expression was negatively correlated with histological grade and poor patient prognosis. NXF1 inhibited ECa cell proliferation, colony formation, migration, and invasion in vitro, and suppressed tumor growth and metastasis in vivo. Mechanistically, NXF1 interferes with the binding of SRSF3 to exon 3 of SP4, preventing the formation of the “cancerous” long SP4 isoform (L-SP4) and promoting the “noncancerous” short SP4 isoform (S-SP4), which lacks the transactivation domain. In conclusion, NXF1 suppresses ECa tumorigenicity and progression through an SRSF3-mediated SP4 alternative splicing mechanism, and could serve as a novel prognostic biomarker for clinical intervention in ECa.