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Preoperative elevations in the levels of serum amyloid A ( SAA) or C-reactive protein ( CRP) have been reported to be prognostic indicators in several malignancies. The aim of this study is to evaluate the serum levels of SAA and CRP in the prognosis of esophageal squamous cell carcinoma ( ESCC). In total, 252 patients with ESCC who had undergone surgery with curative-intent were retrospectively recruited. The specificity, sensitivity, and prognostic value of SAA or CRP levels were measured as the area under the receiver operating characteristic ( ROC) curve ( AUC). The clinical value of SAA and CRP levels as prognostic indicators was evaluated using Cox's proportional hazards model. The 1-, 3-, and 5-year overall survival ( OS) rates for the entire cohort of patients with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the levels of SAA and CRP was significant ( r2 = 0. 685, P < 0.001). The ROC analysis showed that the levels of CRP were associated with a significantly lower overall accuracy than were the SAA levels ( AUC, 0.615 vs. 0.880; P < 0.001). For the complete cohort, the median OS was 52.0 months longer in patients with low preoperative serum levels of SAA (72.0 months) compared with patients who had high SAA levels (20.0 months, P < 0.001). The median OS among patients with low CRP levels was also longer compared with the patients who had high CRP levels (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that the preoperative elevated levels of SAA could find significant differences in OS for stage I, stage II, and stage III ( P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the increased levels of CRP could only find a difference in OS for stage II cancers. After a multivariate analysis, preoperative elevated level of SAA was found to be an independently and significant prognostic factor ( P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can act as prognostic factors, and that elevated levels of these proteins are associated with negative effects on the survival of patients with ESCC. SAA showed a higher prognostic value than CRP in both cohort and subgroup analysis. [ABSTRACT FROM AUTHOR]

Background Psoriasis is a chronic, recurrent skin disease that affects approximately 2-3% of the world's population, and can significantly impair patients' wellbeing and their physical and mental functioning. Aim To systematically evaluate the efficacy and safety of ustekinumab versus placebo for psoriasis. Methods We performed a systematic review of all the relevant published literature relating to randomized controlled trials ( RCTs) of ustekinumab from 1990 to August 2013. Relative ratios ( RRs) and 95% confidence intervals ( CIs) were calculated, and meta-analysis was conducted with Revman5.2.6 software, while GRADE Profile 3.6 was used to evaluate the quality of the evidence. Results In total, 9 RCTs involving 11 381 patients were included. The meta-analysis results were as follows. (i) At the end of 12 weeks, the ustekinumab group had a larger number of patients with improvement in Psoriasis Area and Severity Index ( PASI) of at least 50% ( PASI50), at least 75% ( PASI75) and at least 90% ( PASI90); a larger number with improvement in Physician's Global Assessment ( PGA), and a larger number with improvement in Dermatology Life Quality Index ( DLQI) to a score of 0 or 1 (no effect at all on patient's life). (ii) There was no significant difference in efficacy between 45 mg and 90 mg ustekinumab at the end of 12 weeks. (iii) There was no obvious difference between the ustekinumab and placebo groups in the incidence of adverse events over 5 years. There was also no obvious difference between the two doses of ustekinumab after 5 years. Conclusion Our results indicate that ustekinumab is safe for patients with moderate to severe plaque psoriasis over a period of 5 years, and it is effective after 12 weeks. There was no significant superiority in efficacy between the 45 mg and 90 mg doses for short-term therapy. Results of the long-term safety evaluation are consistent with short-term reports of ustekinumab safety. More long-term studies and RCTs are needed to validate these results. [ABSTRACT FROM AUTHOR]

Recombinant glucose oxidase from Aspergillus niger expressed in Pichia pastoris by fed-batch fermentation was purified and assessed with 1·26 purification fold to homogeneity using Q- Sepharose F. F. chromatography. The enzyme was determined by SDS- PAGE and gradient PAGE, which showed a dimeric form of 150 kDa. The purified r GOD was proved to be a glycoprotein, and the content of which was estimated to be 36·7 and 25·14% by phenol-sulfuric acid and anthrone-sulfuric acid methods. Characteristics demonstrated that the highest activity was in pH 6·0 at 40°C and was stable at a broad pH range from 4·0 to 9·0 at 55°C or below. The optimum substrate for this enzyme was d-glucose, and the Km was 21·06 mmol l−1 as well as the Vmax was 359 μmol min−1 mg−1. r GOD possessed high resistance to various chemicals except for Hg2+, Fe2+, Ag+, Cu2+, 1,4-dithiothreitol, sodium dodecyl sulfate and ascorbic acid. In addition, the inhibitors also exhibited intensive fluorescence quenching effect on r GOD. Significance and Impact of Study Glucose oxidase is a very important enzyme produced by several species. However, large-scale applications have always been postponed by its complexity in fermentation and purification. Our research focused on developing new purification strategy of recombinant GOD from A. niger expressed in P. pastoris. Here, we described this novel one-step purification method and subsequent research in the characteristics of r GOD which showed different results from previous work. These can open new opportunities to increase its application. [ABSTRACT FROM AUTHOR]

Collagenase Clostridium Histolyticum (CCH) is the first medical therapy approved by the FDA to treat Peyronie's Disease (PD). CCH men were older than the IFN cohort (56.9 vs 54.7 years, p=0.03), had a shorter duration of PD (2.3 vs 2.7, p<0.0001), and had a larger pre-treatment curvature (62.3 vs 48.3, p<0.0001). These data would suggest that CCH should be considered preferentially over IFN as an injection therapy for PD. [Extracted from the article]

Transforming growth factor β (TGFβ) signaling has been recently shown to reduce antitumor response to PD-L1 blockade, leading to a renewed enthusiasm in developing anti-TGFβ therapies for potential combination with cancer immunotherapy agents. Inhibition of TGFβ signaling in nonclinical toxicology species is associated with serious adverse toxicities including cardiac valvulopathies and anemia. Previously, cardiovascular toxicities have been thought to be limited to small molecule inhibitors of TGFβ receptor and not considered to be a liability associated with pan-TGFβ neutralizing monoclonal antibodies (mAbs). Here, we report the toxicity findings associated with a potent pan-TGFβ neutralizing mAb (pan-TGFβ mAb; neutralizes TGFβ1, 2, and 3) after 5 weekly intravenous doses of 10, 30, and 100 mg/kg, followed by a 4-week recovery period, in mice and cynomolgus monkeys. Mortality was observed due to acute bleeding and cardiovascular toxicity in mice at ≥ 30 mg/kg and prolonged menstruation in female monkeys at 100 mg/kg. Additional findings considered to be on-target exaggerated pharmacology included generalized bleeding and cardiovascular toxicity in mice and monkeys; histopathologic changes in the teeth, tongue, and skin in mice; and abnormal wound healing and microscopic pathology in the bone in monkeys. Importantly, our data indicate that the cardiovascular toxicities associated with the inhibition of TGFβ signaling are not limited to small molecule inhibitors but are also observed following administration of a potent pan-TGFβ inhibiting mAb. [ABSTRACT FROM AUTHOR]

Aims The study aims to demonstrate the antimicrobial and disinfectant resistance phenotypes and genotypes of Escherichia coli isolates obtained from giant pandas ( Ailuropoda melanoleuca). Methods and Results Antimicrobial testing was performed according to the standard disk diffusion method. The minimal inhibitory concentrations ( MICs) of disinfectants were determined using the agar dilution method. All isolates were screened for the presence of antimicrobial and disinfectant resistance genes and further analysed for genetic relatedness by pulse-field gel electrophoresis ( PFGE). Results showed that 46·6% of the isolates were resistant to at least one antimicrobial. Escherichia coli isolates showed resistance to fewer antimicrobials as panda age increased. Among antimicrobial-resistant E. coli isolates, the antimicrobial resistance genes bla CTX-M (88·2%) and sul1 (92·3%) were most prevalent. The disinfectant resistance genes emrE, ydgE/ydgF, mdfA and sugE(c) were commonly present (68·2-98·9%), whereas qac and sugE(p) were relatively less prevalent (0-21·3%). The frequencies of resistance genes tended to be higher in E. coli isolated in December than in July, and PFGE profiles were also more diverse in isolates in December. The qacEΔ1 and sugE(p) genes were higher in adolescent pandas than in any other age groups. PFGE revealed that antimicrobial resistance correlated well with sampling time and habitat. Conclusions This study demonstrated that antimicrobial and disinfectant resistance was common in giant panda-derived E. coli, and the antimicrobial resistance was associated with sampling time and habitat. Escherichia coli could serve as a critical vector in spreading disinfectant and antimicrobial resistance. Significance and Impact of the Study This is the first study that demonstrated the phenotypic and genetic characterizations of antimicrobial and disinfectant resistance in E. coli isolates from more than 60 giant pandas. Frequent transfer of pandas to other cages may lead to the dissemination of antimicrobial resistance. The study highlights the need for regularly monitoring the antimicrobial and disinfectant resistance in bacteria from giant pandas. [ABSTRACT FROM AUTHOR]

Background: A systematic review and network meta-analysis was undertaken to consider the evidence for the efficacy and tolerability of placebo, cilostazol, naftidrofuryl oxalate and pentoxifylline in patients with intermittent claudication due to peripheral arterial disease (PAD). Methods: MEDLINE, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings, BIOSIS, National Research Register and MetaRegister databases were searched. Eligible studies were randomized controlled trials (RCTs) and published systematic reviews of patients with intermittent claudication due to PAD and whose symptoms persisted despite a period of conservative management. Study selection was conducted by one reviewer with involvement from a clinician. Data were extracted by one reviewer with no blinding to authors or journal, and checked by a second reviewer. Outcome measures were maximum walking distance (MWD) and pain-free walking distance (PFWD). Results: The review identified 1876 citations; 26 RCTs met the inclusion criteria for the systematic review. Eleven trials provided data relevant for the meta-analysis. Naftidrofuryl oxalate was ranked first for both MWD and PFWD (probability of 0·947 and 0·987, respectively, of being the best treatment) followed by cilostazol and pentoxifylline. For naftidrofuryl oxalate, cilostazol and pentoxifylline, MWD increased by 60 (95 per cent credible interval 20 to 114) per cent, 25 (11 to 40) per cent and 11 (−1 to 24) per cent respectively relative to placebo, and PFWD increased by 49, 13 and 9 per cent. Conclusion: Naftidrofuryl oxalate and cilostazol are both effective treatments for claudication; naftidrofuryl oxalate is likely to be the most effective, with minimal serious adverse events. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a study on three novel mutations of the ectodysplasin A (EDA) gene in Chinese patients with X-linked hypohidrotic ectodermal dysplasia (XLHED). The researchers believe that a pathogenic mutation located in the introns or other regulatory regions might be responsible for the disease phenotype. Furthermore, the study revealed evidence for an unequal homologous recombination between two LINE-1 elements as the molecular mechanism in the pathogenesis of XLHED.

Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-κB (NF-κB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-κB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-κB-dependent gene, intercellular adhesion molecule-1. The NF-κB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-κB activity. The enhanced activation of NF-κB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-κB inhibitor, IκBβ, but not IκBα. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-κB, was not involved in the regulation of NF-κB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-κB under certain circumstances. [ABSTRACT FROM AUTHOR]

T cell immunity to lytic proteins of herpesviruses is important in host control of infection. We have characterized the cytotoxic T lymphocyte (CTL) response to 5 human herpesvirus 8 (HHV-8) homologues of lytic proteins in HHV-8-seropositive individuals. HLA class I-restricted, CD8(+) CTL responses to >/=1 HHV-8 lytic protein were detected in all 14 HHV-8-seropositive study subjects tested, with or without human immunodeficiency virus type 1 (HIV-1) infection, but not in any of 5 HHV-8-seronegative individuals. Seven of these study subjects with both HHV-8 and HIV-1 infection had greater anti-CTL reactivity to glycoprotein H (open-reading frame 22) than did the 7 study subjects infected only with HHV-8. Moreover, there was a strong, inverse correlation between HIV-1 load and glycoprotein H-specific CTL lysis in the study subjects infected with both viruses. CTL reactivity to HHV-8 lytic proteins may be involved in host control of HHV-8-related diseases, such as Kaposi's sarcoma. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Systematic review and economic evaluation of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease" in a 2011 issue is presented.