Interferon-gamma inducible protein 10 (IP10) induced cisplatin resistance of HCC after liver transplantation through ER stress signaling pathway.

Tumor recurrence remains an obstacle after liver surgery, especially in living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC). The acute-phase liver graft injury might potentially induce poor response to chemotherapy in recurrent HCC after liver transplantation. We here intended to explore the mechanism and to identify a therapeutic target to overcome such chemoresistance. The associations among graft injury, overexpression of IP10 and multidrug resistant genes were investigated in a rat liver transplantation model, and further validated in clinical cohort. The role of IP10 on HCC cell proliferation and tumor growth under chemotherapy was studied both in vitro and in vivo. The underlying mechanism was revealed by detecting the activation of endoplasmic reticulum (ER) stress signaling pathways. Moreover, the effect of IP10 neutralizing antibody sensitizing cisplatin treatment was further explored. In rat liver transplantation model, significant up-regulation of IP10 associated with multidrug resistant genes was found in small-for-size liver graft. Clinically, high expression of circulating IP10 was significant correlated with tumor recurrence in HCC patients underwent LDLT. Overexpression of IP10 promoted HCC cell proliferation and tumor growth under cisplatin treatment by activation of ATF6/Grp78 signaling. IP10 neutralizing antibody sensitized cisplatin treatment in nude mice. The overexpression of IP10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway. IP10 neutralizing antibody could be a potential adjuvant therapy to sensitize cisplatin treatment

A metaheuristic-based framework for index tracking with practical constraints

Recently, numerous investors have shifted from active strategies to passive strategies because the passive strategy approach affords stable returns over the long term. Index tracking is a popular passive strategy. Over the preceding year, most researchers handled this problem via a two-step procedure. However, such a method is a suboptimal global-local optimization technique that frequently results in uncertainty and poor performance. This paper introduces a framework to address the comprehensive index tracking problem (IPT) with a joint approach based on metaheuristics. The purpose of this approach is to globally optimize this problem, where optimization is measured by the tracking error and excess return. Sparsity, weights, assets under management, transaction fees, the full share restriction, and investment risk diversification are considered in this problem. However, these restrictions increase the complexity of the problem and make it a nondeterministic polynomial-time-hard problem. Metaheuristics compose the principal process of the proposed framework, as they balance a desirable tradeoff between the computational resource utilization and the quality of the obtained solution. This framework enables the constructed model to fit future data and facilitates the application of various metaheuristics. Competitive results are achieved by the proposed metaheuristic-based framework in the presented simulation

An investigation of the effectiveness of human resource management in the Hong Kong police

In the literature, there is the increasing trend to link human resource planning with strategic planning giving greater importance to, and greater involvement of, human resource management in organization strategy. Also the Hong Kong Police is a manpower oriented discipline force and the human resource management functions play a critical role in the effective management of these human resources. Therefore, the critical nature of the human resource management of the Hong Kong Police justifies a management report orientation where the focus is on the production of positive and practical recommendations. The objectives of the report are to evaluate the effectiveness of the existing human resource management system of the Hong Kong Police and also if and where appropriate to make recommendations designed to enhance the present system. In order to achieve the objectives, four aspects were evaluated. The first aspect is the human resource management goals of the Hong Kong Police. It was evaluated against the criteria of the extent to which it is consistent with the ii Vision, Statement of the Common Purposes and Values of the Police. The second aspect is its policies and practices of the each of the functions, which include 1. human resource planning (HRP), 2. recruitment and selection, 3. training and career development, 4. compensation and benefits management, 5. performance evaluation, 6. employee and labor relations, 7. counseling and 8. termination of the existing human resource management. It was evaluated through the comparison between the policies and practices of the each of the functions mentioned above and the corresponding theoretical functional goals. The third aspect is outcomes of human resource management, including complaints from the public, and opinions to it from the general public. It was evaluated against the overall goals of human resource management of the Hong Kong Police. The last but not the least, others, which are the things other than the above, factors viewed as relevant including what it has done during 1996 to 1999. Peters and Waterman Model was used as a framework for evaluating how well the Police was doing during this period. After considering all the aspects, we concluded that the Hong Kong Police did well in the planning process of the human resource management, as theoretically, the effectiveness of the human resource management was achieved. However, further improvement is needed in certain areas concerning the actual performance during the implementation, which may imply there are some problems that may affect the effectiveness of the human resource management of the Hong Kong Police. Based on the evaluation, we suggest that Competency Assessment Methods can be used as a framework for the Hong Kong Police to develop a set of competency for evaluating the performance of the employees. Also, a number of ways were suggested to improve the existing promotion mechanism. The supervisor’s recommendation involved in it can be improved by giving guidelines to the supervisors and having a group of supervisors to evaluate the performance of the employee. Also the recommendations should base on credible information. Moreover, feedback channels should be given to the employees to raise their opinions towards the decision in the promotion mechanism. In order to improve the competency of the supervisors, training should be given to strengthen their accountability for handling their work. Also a flexible and cafeteria benefits package was recommended to increase the flexibility of the existing benefits package iv for motivating the employees by giving autonomy to choose the benefits they need

Hepatoprotective effects of berberine on carbon tetrachloride-induced acute hepatotoxicity in rats

Background: Berberine is an active compound in Coptidis Rhizoma (Huanglian) with multiple pharmacological activities including antimicrobial, antiviral, anti-inflammatory, cholesterol-lowering and anticancer effects. The present study aims to determine the hepatoprotective effects of berberine on serum and tissue superoxide dismutase (SOD) levels, the histology in tetrachloride (CCl 4)-induced liver injury.Methods: Sprague-Dawley rats aged seven weeks were injected intraperitoneally with 50% CCl 4 in olive oil. Berberine was orally administered before or after CCl 4 treatment in various groups. Twenty-four hours after CCl 4 injection, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, serum and liver superoxide dismutase (SOD) activities were measured. Histological changes of liver were examined with microscopy.Results: Serum ALT and AST activities significantly decreased in a dose-dependent manner in both pre-treatment and post-treatment groups with berberine. Berberine increased the SOD activity in liver. Histological examination showed lowered liver damage in berberine-treated groups.Conclusion: The present study demonstrates that berberine possesses hepatoprotective effects against CCl 4-induced hepatotoxicity and that the effects are both preventive and curative. Berberine should have potential for developing a new drug to treat liver toxicity. © 2010 Feng et al; licensee BioMed Central Ltd.published_or_final_versio

Genome-Wide Association Study of Hepatocellular Carcinoma in Southern Chinese Patients with Chronic Hepatitis B Virus Infection

One of the most relevant risk factors for hepatocellular carcinoma (HCC) development is chronic hepatitis B virus (HBV) infection, but only a fraction of chronic HBV carriers develop HCC, indicating that complex interactions among viral, environmental and genetic factors lead to HCC in HBV-infected patients. So far, host genetic factors have incompletely been characterized. Therefore, we performed a genome-wide association (GWA) study in a Southern Chinese cohort consisting of 95 HBV-infected HCC patients (cases) and 97 HBV-infected patients without HCC (controls) using the Illumina Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs) were then validated in an independent cohort of 500 cases and 728 controls. 4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12 showed consistent association in both the GWA and replication phases (ORcombined = 1.31–1.39; pcombined = 2.71×10−5–5.19×10−4; PARcombined = 26–31%). We found a 2.3-kb expressed sequence tag (EST) in the region using in-silico data mining and verified the existence of the full-length EST experimentally. The expression level of the EST was significantly reduced in human HCC tumors in comparison to the corresponding non-tumorous liver tissues (P<0.001). Results from sequence analysis and in-vitro protein translation study suggest that the transcript might function as a long non-coding RNA. In summary, our study suggests that variations at chromosome 8p12 may promote HCC in patients with HBV. Further functional studies of this region may help understand HBV-associated hepatocarcinogenesis

Hybrid split-arc partial-field volumetric modulated arc therapy: an improved beam arrangement for linear accelerator-based hippocampal-avoidance whole brain radiation therapy

Background: This technical note aims to verify the hippocampus and adjacent organs at risk (OARs) sparing ability of an improved beam arrangement, namely hybrid split-arc partial-field volumetric modulated arc therapy (VMAT) (Hsapf-VMAT) during whole brain radiation therapy (WBRT). Materials and methods: Computed tomography simulation images of 22 patients with brain metastases were retrieved in this retrospective planning study. The hippocampus was manually delineated according to the criterion of RTOG 0933. Plans delivering 30 Gy in 10 fractions were generated for each patient using split-arc partial-field VMAT (sapf-VMAT) and Hsapf-VMAT. The sapf-VMAT plans consisted of 4 arc fields of 179.9° each with reduced field size. The Hsapf-VMAT consisted of 4 arc fields similar to sapf-VMAT in addition to 2 lateral opposing static fields. Statistical comparisons between treatment plans of both techniques were performed using the paired t-test at 5% level significance. Results: The results demonstrated that Hsapf-VMAT can achieve superior dose sparing in hippocampus which is comparable to sapf-VMAT (p &gt; 0.05). In both eyes, Hsapf-VMAT had significantly lower Dmean and Dmax compared to sapf-VMAT (p &lt; 0.005). Decrease in Dmax of both lenses using Hsapf-VMAT (p &lt; 0.005) were statistically significant when compared to sapf-VMAT. Hsapf-VMAT demonstrated significant reduction of Dmean and Dmedian to the optic nerves (p &lt; 0.05). Whole brain planning target volume (PTV) coverage was not compromised in both techniques. Conclusion: The present study adopts a hybrid technique, namely Hsapf-VMAT, for hippocampal sparing WBRT. Hsapf-VMAT can achieve promising dose reduction to the hippocampus, both eyes and lenses. Therefore, Hsapf-VMAT can be considered an improved version of sapf-VMAT

Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism

<p>Abstract</p> <p>Background</p> <p>Two active compounds, baicalein and its glycoside baicalin were found in the dried root of <it>Scutellaria baicalensis </it>Georgi, and reported to be neuroprotective <it>in vitro </it>and <it>in vivo</it>. This study aims to evaluate the protective effects of baicalein on the rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to parkinsonism.</p> <p>Methods</p> <p>Cell viability and cytotoxicity were determined by MTT assay. The degree of nuclear apoptosis was evaluated with a fluorescent DNA-binding probe Hoechst 33258. The production of reactive oxidative species (ROS) and loss of mitochondrial membrane potential (ΔΨm) were determined by fluorescent staining with DCFH-DA and Rhodanmine 123, respectively. The expression of Bax, Bcl-2, cleaved caspase-3 and phosphorylated ERK1/2 was determined by the Western blots.</p> <p>Results</p> <p>Baicalein significantly increased viability and decreased rotenone-induced death of SH-SY5Y cells in a dose-dependent manner. Pre- and subsequent co-treatment with baicalein preserved the cell morphology and attenuated the nuclear apoptotic characteristics triggered by rotenone. Baicalein antagonized rotenone-induced overproduction of ROS, loss of ΔΨm, the increased expression of Bax, cleaved caspase-3 and phosphorylated ERK1/2 and the decreased expression of Bcl-2.</p> <p>Conclusion</p> <p>The antioxidative effect, mitochondrial protection and modulation of anti-and pro-apoptotic proteins are related to the neuroprotective effects of baicalein against rotenone induced cell death in SH-SY5Y cells.</p

The psychophysiological effects of Tai-chi and exercise in residential Schizophrenic patients: a 3-arm randomized controlled trial

BACKGROUND: Patients with schizophrenia are characterized by high prevalence rates and chronicity that often leads to long-term institutionalization. Under the traditional medical model, treatment usually emphasizes the management of psychotic symptoms through medication, even though anti-psychotic drugs are associated with severe side effects, which can diminish patients’ physical and psychological well-being. Tai-chi, a mind-body exercise rooted in Eastern health philosophy, emphasizes the motor coordination and relaxation. With these potential benefits, a randomized controlled trial (RCT) is planned to investigate the effects of Tai-chi intervention on the cognitive and motor deficits characteristic of patients with schizophrenia. METHODS/DESIGN: A 3-arm RCT with waitlist control design will be used in this study. One hundred and fifty three participants will be randomized into (i) Tai-chi, (ii) exercise or (iii) waitlist control groups. Participants in both the Tai-chi and exercise groups will receive 12-weeks of specific intervention, in addition to the standard medication and care received by the waitlist control group. The exercise group will serve as a comparison, to delineate any unique benefits of Tai-chi that are independent of moderate aerobic exercise. All three groups will undergo three assessment phases: (i) at baseline, (ii) at 12 weeks (post-intervention), and (iii) at 24 weeks (maintenance). All participants will be assessed in terms of symptom management, motor coordination, memory, daily living function, and stress levels based on self-perceived responses and a physiological marker. DISCUSSION: Based on a promising pilot study conducted prior to this RCT, subjects in the Tai-chi intervention group are expected to be protected against deterioration of motor coordination and interpersonal functioning. They are also expected to have better symptoms management and lower stress level than the other treatment groups. TRIAL REGISTRATION: The trail has been registered in the Clinical Trials Center of the University of Hong Kong (HKCTR-1453)

FTY720 Suppresses Liver Tumor Metastasis by Reducing the Population of Circulating Endothelial Progenitor Cells

Background: Surgical procedures such as liver resection and liver transplantation are the first-line treatments for hepatocellular carcinoma (HCC) patients. However, the high incidence of tumor recurrence and metastasis after liver surgery remains a major problem. Recent studies have shown that hepatic ischemia-reperfusion (I/R) injury and endothelial progenitor cells (EPCs) contribute to tumor growth and metastasis. We aim to investigate the mechanism of FTY720, which was originally applied as an immunomodulator, on suppression of liver tumor metastasis after liver resection and partial hepatic I/R injury. Methodology/Principal Findings: An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777. Two weeks after orthotopic liver tumor implantation, the rats underwent liver resection for tumor-bearing lobe and partial hepatic I/R injury. FTY720 (2 mg/kg) was administered through the inferior caval vein before and after I/R injury. Blood samples were taken at days 0, 1, 3, 7, 14, 21 and 28 for detection of circulating EPCs (CD133+CD34+). Our results showed that intrahepatic and lung metastases were significantly inhibited together with less tumor angiogenesis by FTY720 treatment. The number of circulating EPCs was also significantly decreased by FTY720 treatment from day 7 to day 28. Hepatic gene expressions of CXCL10, VEGF, CXCR3, CXCR4 induced by hepatic I/R injury were down-regulated in the treatment group. Conclusions/Significance: FTY720 suppressed liver tumor metastasis after liver resection marred by hepatic I/R injury in a rat liver tumor model by attenuating hepatic I/R injury and reducing circulating EPCs. © 2012 Li et al.published_or_final_versio

Development of a multi-locus sequence typing scheme for Laribacter hongkongensis, a novel bacterium associated with freshwater fish-borne gastroenteritis and traveler's diarrhea

<p>Abstract</p> <p>Background</p> <p>Laribacter hongkongensis is a newly discovered, facultative anaerobic, Gram-negative, motile, sea gull-shaped rod associated with freshwater fish borne gastroenteritis and traveler's diarrhea. A highly reproducible and discriminative typing system is essential for better understanding of the epidemiology of <it>L. hongkongensis</it>. In this study, a multilocus sequence typing (MLST) system was developed for <it>L. hongkongensis</it>. The system was used to characterize 146 <it>L. hongkongensis </it>isolates, including 39 from humans and 107 from fish.</p> <p>Results</p> <p>Fragments (362 to 504 bp) of seven housekeeping genes were amplified and sequenced. Among the 3068 bp of the seven loci, 332 polymorphic sites were observed. The median number of alleles at each locus was 34 [range 22 (<it>ilvC</it>) to 45 (<it>thiC</it>)]. All seven genes showed very low <it>d</it>_<it>n</it>/<it>d</it>_{<it>s </it>}ratios of < 0.04, indicating that no strong positive selective pressure is present. A total of 97 different sequence types (STs) were assigned to the 146 isolates, with 80 STs identified only once. The overall discriminatory power was 0.9861. eBURST grouped the isolates into 12 lineages, with six groups containing only isolates from fish and three groups only isolates from humans. Standardized index of association (<it>I</it>^<it>S</it>_<it>A</it>) measurement showed significant linkage disequilibrium in isolates from both humans and fish. The <it>I</it>^<it>S</it>_{<it>A </it>}for the isolates from humans and fish were 0.270 and 0.636, indicating the isolates from fish were more clonal than the isolates from humans. Only one interconnected network (<it>acnB</it>) was detected in the split graphs. The P-value (P = 0) of sum of the squares of condensed fragments in Sawyer's test showed evidence of intragenic recombination in the <it>rho, acnB </it>and <it>thiC </it>loci, but the P-value (P = 1) of maximum condensed fragment in these gene loci did not show evidence of intragenic recombination. Congruence analysis showed that all the pairwise comparisons of the 7 MLST loci were incongruent, indicating that recombination played a substantial role in the evolution of <it>L. hongkongensis</it>. A website for <it>L. hongkongensis </it>MLST was set up and can be accessed at <url>http://mlstdb.hku.hk:14206/MLST_index.html</url>.</p> <p>Conclusion</p> <p>A highly reproducible and discriminative MLST system was developed for <it>L. hongkongensis</it>.</p