Association of circulating calprotectin with lipid profile in axial spondyloarthritis

Calprotectin (CPT) is released during inflammation, also in the context of atherosclerosis. The link between CPT and the atherosclerotic process was evaluated in several diseases. However, studies in axial spondyloarthritis (axSpA), associated with a high incidence of subclinical atherosclerosis, are scarce. Therefore, we assessed the association of CPT with subclinical atherosclerosis and metabolic risk factors in axSpA. CPT serum levels were measured by enzyme-linked immunosorbent assay in 163 axSpA patients and 63 controls. Subclinical atherosclerosis was determined in patients by carotid ultrasonography (assessing the presence/absence of carotid plaques and carotid intima-media thickness [cIMT]). Data on inflammation, disease activity, lipid profile and treatment were collected to evaluate its relationship with CPT. axSpA patients evidenced lower CPT levels than controls. CPT showed no association with plaques or cIMT in axSpA. CPT and HDL-cholesterol negatively correlated, while a positive association of CPT with the atherogenic index was disclosed. Additionally, axSpA patients with C-reactive protein values at diagnosis higher than 3?mg/L displayed higher CPT levels. Our study shows no relationship between CPT and markers of subclinical atherosclerosis in axSpA. Nevertheless, it demonstrates an association of CPT with adverse lipid profiles and inflammatory biomarkers, which could further influence on the development of atherosclerosis.We wish to thank all the patients and controls that participated in this study and Begoña Ubilla for technical assistance. FG is a recipient of a Sara Borrell post-doctoral fellowship from the Instituto de Salud Carlos III (ISCIII) (Spain), co-funded by the European Social Fund (ESF, “Investing in your future”) (grant CD15/00095). SR-M is supported by funds of the RETICS Program (RIER) RD16/0012/0009 (ISCIII, co-funded by the European Regional Development Fund, ERDF). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ERDF). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the ESF (grant CP16/00033). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

Identification of N-Glycosylation in Hepatocellular Carcinoma Patients’ Serum with a Comparative Proteomic Approach

AIM: This study is to explore the different expressions of serum N-glycoproteins and glycosylation sites between hepatocellular carcinoma (HCC) patients and healthy controls. METHOD: We combined high abundant proteins depletion and hydrophilic affinity method to enrich the glycoproteins. Through liquid chromatography-tandem mass spectrometry (LC-MS/MS), we extensively surveyed different expressions of glycosylation sites and glycoproteins between the two groups. RESULT: This approach identified 152 glycosylation sites and 54 glycoproteins expressed differently between HCC patients and healthy controls. With the absolute values of Pearson coefficients of at least 0.8, eight proteins were identified significantly up or down regulated in HCC serum. Those proteins are supposed to be involved in several biological processes, cellular components and molecular functions of hepatocarcinogenesis. Several of them had been reported abnormally regulated in several kinds of malignant tumors, and may be promising biomarkers of HCC. CONCLUSION: Our work provides a systematic and quantitative method of glycoproteomics and demonstrates some key changes in clinical HCC serum. These proteomic signatures may help to unveil the underlying mechanisms of hepatocarcinogenesis and may be useful for the exploration of candidate biomarkers

SIRT3 protects from hypoxia and staurosporine-mediated cell death by maintaining mitochondrial membrane potential and intracellular pH

Mitochondrial sirtuin 3 (SIRT3) mediates cellular resistance toward various forms of stress. Here, we show that in mammalian cells subjected to hypoxia and staurosporine treatment SIRT3 prevents loss of mitochondrial membrane potential (ΔΨ(mt)), intracellular acidification and reactive oxygen species accumulation. Our results indicate that: (i) SIRT3 inhibits mitochondrial permeability transition and loss of membrane potential by preventing HKII binding to the mitochondria, (ii) SIRT3 increases catalytic activity of the mitochondrial carbonic anhydrase VB, thereby preventing intracellular acidification, Bax activation and apoptotic cell death. In conclusion we propose that, in mammalian cells, SIRT3 has a central role in connecting changes in ΔΨ(mt), intracellular pH and mitochondrial-regulated apoptotic pathways

Skeletal muscle metastasis from the most common carcinomas orthopedic surgeons deal with. A systematic review of the literature

There is scarce information in the literature dealing with the clinical presentation, management and oncologic outcomes of skeletal muscle metastases (SMM). We sought to perform a systematic review of the literature to investigate: (1) tumor characteristics of SMM, (2) therapeutic approach, and (3) oncological outcomes. A systematic review of the literature was performed using PubMed and EMBASE search engines. A total of 3231 references were reviewed and 49 studies were included. Demographic data, presentation characteristics, and oncological outcomes were recorded. Statistical analysis was performed using SPSS 22.0 software (IBM; Armonk, New York) and Comprehensive Meta-Analysis software version 3 (Biostat, Inc.), with p < 0.05 as statistically significant. A total of 231 patients were included. These tumors presented more commonly on males 58.4% (135/231), with a mean age of 60.08 ± 10.6 years, and in the axial area 39.6% (88/222). The most common carcinoma type was lung 41.1% (95/231). Resection of a single metastases did not change survival significantly (p = 0.992). LRR was higher within the group of patients that underwent WLE compared with non-WLE [31.3% (23/74) vs. 8.7% (2/23), p ≤ 0.001]. Kaplan-Meier survival analysis for the entire cohort showed an estimate of 15.3 months [95% confidence interval (CI) 11.6-19; standard error (SE) 0.432], with lung carcinoma carrying the worst prognosis 6.7 months (95% CI 5.4-8.07; SE 0.68). Patients with a single SMM showed a worse estimate mean survival time compared to patients with multiple metastases limited to muscles [8.6 months (95% CI 4.7-12.5; SE 2.0) vs 25.4 months (95% CI 19.8-31.05; SE 2.8; p ≤ 0.001)]. Overall survival is poor and is driven mainly by the type of carcinoma. An Increased LRR might be present due to the systemic nature of the condition, and degree of control of the primary carcinoma