Diagnostic Value of Serum Chitinase-3-Like Protein 1 for Liver Fibrosis: A Meta-analysis.

Background: Serum chitinase-3-like protein 1 (CHI3L1) is a promising marker for diagnosing liver fibrosis. This meta-analysis was carried out to assess the diagnostic performance of serum CHI3L1 for the estimation of liver fibrosis. Methods: Systematic searches were performed on PubMed, Embase, Web of Science, Scopus, the Cochrane Library, Google Scholar, Sinomed, the China National Knowledge Infrastructure (CNKI), the Chinese Medical Journal Database, and the Wanfang databases for available studies. The primary studies were screened strictly according to inclusion and exclusion criteria, and sensitivity, specificity, and other measures of accuracy of serum CHI3L1 for evaluating liver fibrosis were pooled with 95% confidence intervals. I 2 was calculated to assess heterogeneity, and sources of heterogeneity were explored by subgroup analysis. Deeks' test was used to assess for publication bias, and likelihood ratio was used to determine posttest probability. Results: Our research integrated 11 articles, accounting for 1897 patients older than 18 years old. The pooled sensitivity and specificity for significant fibrosis, advanced fibrosis, and cirrhosis were 0.79 and 0.82 with an area under the receiver operating characteristic curve (AUC) of 0.85, 0.81 and 0.83 with an AUC of 0.91, and 0.72 and 0.74 with an AUC of 0.85, respectively. Random-effects models were used to assess for significant heterogeneity, and subgroup analysis showed that age and aetiology of included patients were likely sources of heterogeneity. No potential publication bias was found for serum CHI3L1 in the diagnosis of significant fibrosis, advanced fibrosis, or cirrhosis, and posttest probability was moderate. Conclusion: Measurement of serum CHI3L1 is a feasible diagnostic tool for liver fibrosis.

The diagnostic value of serum creatinine and cystatin c in evaluating glomerular filtration rate in patients with chronic kidney disease: a systematic literature review and meta-analysis.

BACKGROUND: Serum biomarkers, such as serum creatinine (SCr) and serum cystatin C (SCysC), have been widely used to evaluate renal function in patients who have chronic kidney disease (CKD). OBJECTIVE: This article aims to assess the value of determining SCr and SCysC levels in patients that have long-term kidney disease. Approaches: MEDLINE, EmBase, the Cochrane Library and other databases were searched using both MeSH terms and text words to collect research that assessed the diagnostic value of using SCr and SCysC to evaluate Glomerular Filtration Rate (GFR) in patients with CKD. Data were converted into fourfold tables. Summary Receiver Operating Characteristic Curves and meta-analyses were accomplished via Meta-Disc version 1.4. RESULTS: In total, 21 relevant articles involving 3112 study subjects were included in our review. Results showed that the collective sensitivity for SCr and SCysC was 0.77 (95% CI: 0.69-0.84) and 0.87 (95% CI: 0.82-0.91), respectively. The pooled specificity for SCr and SCysC was 0.91 (95% CI: 0.86-0.94) and 0.87 (95% CI: 0.82-0.91), respectively. Subgroup analyses demonstrated that when GFR cut-off values are set to 60 (ml/min/1.73 m2), the pooled sensitivity is 0.94 (95% CI: 0.90-0.96) for SCysC and 0.75 (95% CI: 0.68-0.82) for SCr. CONCLUSIONS: The diagnostical accuracy for impaired kidney function favors SCysC. Confidence intervals for the pooled sensitivity and specificity for SCr and SCysC overlap. However, SCysC is more sensitive for estimating GFR than SCr when GFR cut-off values are set to 60 (ml/min/1.73 m2).

Evening versus morning dosing regimen drug therapy for chronic kidney disease patients with hypertension in blood pressure patterns: a systematic review and meta-analysis.

BACKGROUND: Evening dosing regimen drug therapy on blood pressure (BP) control is used widely, but its clinical benefits and preservation or re-establishment of the normal 24-h BP dipping pattern in chronic kidney disease (CKD) patients is not known. AIMS: To investigate the effect of an evening dosing regimen of antihypertensive drugs on BP patterns of CKD patients with hypertension. METHODS: A systematic review was conducted by searching PUBMED, EMBASE, ASN-ONLINE, the Cochrane Library and the reference lists of relevant articles of published papers. All trials designed to evaluate the effects of evening versus morning dosing regimen drug therapy for CKD patients with hypertension were included. Meta-analysis was performed using random or fixed effects models. RESULTS: Five randomised controlled trials and one comparative study, including 3732 patients, met the inclusion criteria. Compared with morning dosing regimen drug therapy, evening administration of antihypertensive medication was associated with a significant reduction of 40% in non-dipper BP patterns (risk ratio (RR), 95% CI, (0.43, 0.84)). We noted a significant decrease in nocturnal systolic blood pressure (SBP) (MD -3.17 mmHg, 95% CI (-5.41, -0.94)), a significant reduction in nocturnal diastolic blood pressure (DBP) (MD -1.37 mmHg, 95% CI (-2.05, -0.69)) and a significant increase in awake SBP (MD 1.15 mmHg, 95% CI (0.10, 2.19)) in patients assigned to the evening dosing regimen drug therapy group. Patients showed no significant differences for all-cause mortality and cardiovascular mortality. CONCLUSION: This review shows that evening dosing regimen drug therapy could reverse non-dipper BP patterns in hypertensive CKD patients.

EB1 promotes Aurora-B kinase activity through blocking its inactivation by protein phosphatase 2A.

EB1 (end-binding protein 1) is a key player in the regulation of microtubule dynamics. In concert with its binding partners, adenomatous polyposis coli and p150(glued), EB1 plays a crucial role in a variety of microtubule-based cellular processes. In this study we have identified in a yeast two-hybrid screen the mitotic kinase and chromosome passenger protein Aurora-B as a binding partner of EB1. GST pull-down and immunoprecipitation experiments reveal a specific interaction between Aurora-B and EB1 both in cells and in vitro. Immunofluorescence microscopy shows that these two proteins colocalize on the central spindle in anaphase and in the midbody during cytokinesis. Kinase assays using both immunoprecipitated and purified Aurora-B demonstrate that EB1 is not a substrate of Aurora-B. Rather, EB1 positively regulates Aurora-B kinase activity. EB1 overexpression remarkably enhances Aurora-B activity and knockdown of its expression impairs Aurora-B activity. Our data further show that EB1 is able to protect Aurora-B from dephosphorylation/inactivation by protein phosphatase 2A (PP2A) by blocking PP2A binding to Aurora-B. These findings establish Aurora-B as an EB1-interacting protein and suggest that EB1 stimulates Aurora-B activity through antagonizing its dephosphorylation/inactivation by PP2A.

Analysis of microtubule-mediated intracellular viral transport.

Host microtubules and motor proteins are crucial to the intracellular transport of a number of viruses. Disruption of microtubules or suppression of motor functions can remarkably inhibit the movement of viruses in host cells. It is now known that incoming viruses use motor proteins to travel along microtubules from the plasma membrane to the nuclear or perinuclear replication site, whereas progeny viruses depend on microtubules and motors to move from the assembly site to the cell periphery. Here, we describe several major methods for analyzing microtubule-mediated intracellular viral transport, using adenovirus as an example.

Inhibition of the mitotic kinesin Eg5 up-regulates Hsp70 through the phosphatidylinositol 3-kinase/Akt pathway in multiple myeloma cells.

The microtubule-dependent motor protein Eg5 plays a critical role in spindle assembly and maintenance in mitosis. Herein we show that the suppression of Eg5 by a specific inhibitor arrested mitosis, induced apoptosis, and up-regulated Hsp70 in human multiple myeloma cells. Mechanistically, Hsp70 induction occurred at the transcriptional level via a cis-regulatory DNA element in Hsp70 promoter and was mediated by the phosphatidylinositol 3-kinase/Akt pathway. Eg5 inhibitor-mediated Hsp70 up-regulation is cytoprotective because blocking Hsp70 induction directly by antisense or small interfering RNA or indirectly by inhibiting the phosphatidylinositol 3-kinase/Akt pathway significantly increased Eg5 inhibitor-induced apoptosis. Furthermore, a farnesyltransferase inhibitor interacted synergistically with the Eg5 inhibitor in inducing apoptosis through disrupting the Akt/Hsp70 signaling axis. These findings provide the first evidence for Eg5 inhibitor activity in hematologic malignancy and identify Hsp70 up-regulation as a critical mechanism responsible for modulating myeloma cell sensitivity to Eg5 inhibitors. In addition, these findings suggest that a combination of Eg5 inhibitors with agents abrogating Hsp70 induction would be useful for myeloma therapy in the clinic.

Effect of genetic variation on human cytochrome p450 reductase-mediated paraquat cytotoxicity.

Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) is a widely used herbicide and is highly toxic to human and animals. The mechanisms of paraquat toxicity involve the generation of superoxide anion through the process of redox cycling. NADPH-cytochrome P450 oxidoreductase (POR) has been reported to be a major enzyme for one-electron reduction of paraquat that initiates the redox cycling. Recently, a total of six missense variants of human POR have been identified in patients with discorded steroidogenesis. However, the effect of these genetic variations on POR-mediated paraquat toxicity is not known. Using the Flp-In Chinese hamster ovary (CHO) cells stably expressing either mouse or human POR and the cells with POR knockdown by siRNA, we confirmed that POR is responsible for paraquat-induced cytotoxicity. We further used this validated system to compare paraquat-induced toxicity among the cells that stably expressed wild-type human POR and its natural variants. While there was no difference in paraquat-induced toxicity between the cells expressing wild-type human POR and the Cys569Tyr variant, the toxicity in cells expressing all the other variants (Tyr181Asp, Ala287Pro, Arg457His, Val492Glu, and Val608Phe) was significantly decreased. Our results provide further evidence on the important role of POR in paraquat-induced toxicity and suggest that individuals carrying the functional variant POR alleles may have an altered susceptibility to paraquat exposure.

[Characterization of cry gene and broad spectrum against lepidopteran of Bacillus thuringiensis subsp. colmeri 15A3].

Bacillus thuringiensis wild type strain 15A3 belongs to subspecies colmeri serotype H-21. RFLP and PCR analysis show that it contains six types of ICP genes: cry1Aa, cry1Ac, cry1Ca, cry1D, cry1I and cry. The sequence of the 1.45 kb N-terminal fragment of cry1Aa differed from that of published. SDS-PAGE showed that the crystal consists of proteins with molecular weight about 130, 79, 70, 65, 51 and 45 kD. Strain 15A3 didn't sysnthesize heat-stable beta-exotoxins according to test of house fly aberration. The 1.2 tons fermentative production exhibited high toxicity against three lepidopteran pests: H. armigera, S. exigua and H. cunea. It was proved that wild type strain can produce a broad specturm of ICP.