Myeloid-specific SIRT1 Deletion Aggravates Hepatic Inflammation and Steatosis in High-fat Diet-fed Mice

Sirtuin 1 (SIRT1) is a mammalian NAD⁺-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-κB), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.     

Comparison of a Web-Based Dietary Assessment Tool with Software for the Evaluation of Dietary Records

Background

Dietary assessment in clinical practice is performed by means of computer support, either in the form of a web-based tool or software. The aim of the paper is to present the results of the comparison of a Slovenian web-based tool with German software for the evaluation of four-day weighted paper-and-pencil-based dietary records (paper-DRs) in pregnant women.

Methods

A volunteer group of pregnant women (n=63) completed paper-DRs. These records were entered by an experienced research dietitian into a web-based application (Open Platform for Clinical Nutrition, OPEN, http://opkp.si/en, Ljubljana, Slovenia) and software application (Prodi 5.7 Expert plus, Nutri-Science, Stuttgart, Germany, 2011). The results for calculated energy intake, as well as 45 macro- and micronutrient intakes, were statistically compared by using the non-parametric Spearman’s rank correlation coefficient. The cut-off for Spearman’s rho was set at >0.600.

Results

12 nutritional parameters (energy, carbohydrates, fat, protein, water, potassium, calcium, phosphorus, dietary fiber, vitamin C, folic acid, and stearic acid) were in high correlation (>0.800), 18 in moderate (0.600–0.799), 11 in weak correlation (0.400–0.599), while 5 (arachidonic acid, niacin, alpha-linolenic acid, fluoride, total sugars) did not show any statistical correlation.

Conclusion

Comparison of the results of the evaluation of dietary records using a web-based dietary assessment tool with those using software shows that there is a high correlation for energy and macronutrient content.     

Prognostic significance of lymphovascular or perineural invasion in patients with locally advanced colorectal cancer

Background

This study was designed to evaluate the prognostic significance of the positivity of lymphovascular (LVI) and perineural invasion (PNI) in patients with locally advanced colorectal cancer.

Methods

From January 1999 to December 2009, 1,437 consecutive patients who underwent curative surgery for stage II or III colorectal cancer were analyzed. Patients were then categorized into 4 groups: LVI−/PNI− (n = 850), LVI+ only (n = 178), PNI+ only (n = 271), and LVI+/PNI+ (n = 138).

Results

With a median follow-up period of 56 months, the 5-year overall survival rates of patients with LVI−/PNI−, LVI+ only, PNI+ only, and LVI+/PNI+ were 82%, 73%, 71%, and 56%, respectively (P < .001), and the 5-year disease-free survival rates of patients with LVI−/PNI−, LVI+ only, PNI+ only, and LVI+/PNI+ were 80%, 70%, 65%, and 46%, respectively (P < .001). In multivariate analysis, LVI+/PNI+ was an independent prognostic factor for both overall survival (P < .001) and disease-free survival (P < .001).

Conclusions

Positivity of both LVI and PNI is a strong predictor of overall and disease-free survival in patients with stages II and III colorectal cancer.     

Substituted adamantylphthalimides: Synthesis,antiviral and antiproliferative activity

In this study, three groups of adamantylphthalimides, bearing different substituents at the phthalimide moiety, N-(4′-R²)phthalimidoadamantanes ( 1 – 7 ), 3-[N-(4′-R²)phthalimido]-1-adamantanols ( 8 – 10 ), and 3-[N-(4′-R²)phthalimido]adamantane-1-carboxylic acids ( 11 – 15 ), were synthesized and screened against tumor cells and viruses. The most potent compounds are not substituted at the adamantane and bear an OH or NH₂ substituent at the phthalimide (compounds 3 and 5 ). The antiproliferative activities of compounds 3 and 5 are in the micromolar range, much higher than the one of thalidomide. A minor antiviral activity against cytomegalovirus and varicella-zoster virus was found for compounds 3 and 5 , but these compounds lacked selectivity. The results presented are important for the rational design of the next-generation compounds with anticancer and antiviral activities.     

Unfavorable hip stress distribution after Legg–Calvé–Perthes syndrome: A 25‐year follow‐up of 135 hips

To study the effect of hip and pelvis geometry on development of the hip after Perthes disease, we determined the resultant hip force and contact hip stress distribution in a population of 135 adult hips of patients who had been treated for Perthes disease in childhood. Contra‐lateral hips with no record of disease were taken as the control population. Biomechanical parameters were determined by mathematical models for resultant hip force in one‐legged stance and for contact hip stress, which use as an input the geometrical parameters assessed from anteroposterior radiographs. The mathematical model for stress was upgraded to account for the deviation of the femoral head shape from spherical. No differences were found in resultant hip force and in peak contact hip stress between the hips that were in childhood subject to Perthes disease and the control population, but a considerable (148%) and significant (p < 0.001) difference was found in the contact hip stress gradient index, expressing an unfavorable, steep decrease of contact stress at the lateral acetabular rim. This finding indicates an increased risk of early coxarthritis in hips subject to Perthes disease. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:8–16, 2014.     

Filling accuracy and imprecision of commercial evacuated sodium citrate coagulation tubes

Current recommendations advocate that blood tubes for coagulation testing should be filled not less than 90% of their nominal filling volume, since under- or over-filling >10% may generate unreliable results of some hemostasis assays. This study was hence aimed to explore filling accuracy and precision of commercial blood tubes. Between-lot variations of 3 different lots (20 tubes per lot) of 3.2% citrate blood tubes manufactured by Becton Dickinson, Greiner and Kima were studied. One additional lot from each manufacturer was assessed in triplicate (three series of 20 tubes), to assess within-lot variation. All tubes were first weighed empty and then filled with distilled water by a syringe, under ideal filling conditions. Filled tubes were weighed again, in duplicate. For each 20 tubes series, mean bias (deviation from the ideal tube filling volume) and imprecision (coefficient of variation; CV%) were calculated. All biases were within ±10%. Within-lot and between-lot variation in filling volume was acceptable, and comprised between 0.4 and 2.4%. Greiner tubes were the most accurate (bias, ?1.0 to 2.4%), followed by Kima (bias, ?7.8 to ?5.9%) and Becton Dickinson (bias, ?9.6 to 3.3%) tubes. The highest between-lot difference was noted for Becton Dickinson tubes (up to 12.9%), followed by Greiner and Kima tubes (up to 3.4 and 1.8%, respectively). Although coagulation tubes filling accuracy was within ±10% for all three tested manufacturers, the overall bias was found to be variable among manufacturers and lots. Major effort shall be made by blood tube manufacturers for improving standardization of their products.