Osteocyte deficiency in hip fractures

Osteocytes play a central role in the regulation of bone remodeling. The aim of this study was to explore osteocyte function, and particularly the expression of SOST, a Wnt inhibitor, in patients with hip fractures. Serum sclerostin levels were measured by ELISA. The expression of several osteocytic genes was studied by quantitative PCR in trabecular samples of the femoral head of patients with hip fractures, hip osteoarthritis and control subjects. The presence of sclerostin protein and activated caspase 3 was revealed by immunostaining. There were no significant differences in serum sclerostin between the three groups. Patients with fractures have fewer lacunae occupied by osteocytes (60 ± 5% vs. 64 ± 6% in control subjects, P = 0.014) and higher numbers of osteocytes expressing activated caspase 3, a marker of apoptosis. The proportion of sclerostin-positive lacunae was lower in patients with fractures than in control subjects (34 ± 11% vs. 69 ± 10%, P = 2 × 10(-8)). The proportion of sclerostin-positive osteocytes was also lower in patients. RNA transcripts of SOST, FGF23 and PHEX were also less abundant in fractures than in control bones (P = 0.002, 5 × 10(-6), and 0.04, respectively). On the contrary, in patients with osteoarthritis, there was a decreased expression of SOST and FGF23, without differences in PHEX transcripts or osteocyte numbers. Osteocyte activity is altered in patients with hip fractures, with increased osteocyte apoptosis and reduced osteocyte numbers, as well as decreased transcription of osteocytic genes. Therefore, these results suggest that an osteocyte deficiency may play a role in the propensity to hip fractures

A Multi-Label Predictor for Identifying the Subcellular Locations of Singleplex and Multiplex Eukaryotic Proteins

Subcellular locations of proteins are important functional attributes. An effective and efficient subcellular localization predictor is necessary for rapidly and reliably annotating subcellular locations of proteins. Most of existing subcellular localization methods are only used to deal with single-location proteins. Actually, proteins may simultaneously exist at, or move between, two or more different subcellular locations. To better reflect characteristics of multiplex proteins, it is highly desired to develop new methods for dealing with them. In this paper, a new predictor, called Euk-ECC-mPLoc, by introducing a powerful multi-label learning approach which exploits correlations between subcellular locations and hybridizing gene ontology with dipeptide composition information, has been developed that can be used to deal with systems containing both singleplex and multiplex eukaryotic proteins. It can be utilized to identify eukaryotic proteins among the following 22 locations: (1) acrosome, (2) cell membrane, (3) cell wall, (4) centrosome, (5) chloroplast, (6) cyanelle, (7) cytoplasm, (8) cytoskeleton, (9) endoplasmic reticulum, (10) endosome, (11) extracellular, (12) Golgi apparatus, (13) hydrogenosome, (14) lysosome, (15) melanosome, (16) microsome, (17) mitochondrion, (18) nucleus, (19) peroxisome, (20) spindle pole body, (21) synapse, and (22) vacuole. Experimental results on a stringent benchmark dataset of eukaryotic proteins by jackknife cross validation test show that the average success rate and overall success rate obtained by Euk-ECC-mPLoc were 69.70% and 81.54%, respectively, indicating that our approach is quite promising. Particularly, the success rates achieved by Euk-ECC-mPLoc for small subsets were remarkably improved, indicating that it holds a high potential for simulating the development of the area. As a user-friendly web-server, Euk-ECC-mPLoc is freely accessible to the public at the website http://levis.tongji.edu.cn:8080/bioinfo/Euk-ECC-mPLoc/. We believe that Euk-ECC-mPLoc may become a useful high-throughput tool, or at least play a complementary role to the existing predictors in identifying subcellular locations of eukaryotic proteins

Laparoscopic and open resection for colorectal cancer: an evaluation of cellular immunity

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer is one kind of frequent malignant tumors of the digestive tract which gets high morbidity and mortality allover the world. Despite the promising clinical results recently, less information is available regarding the perioperative immunological effects of laparoscopic surgery when compared with the open surgery. This study aimed to compare the cellular immune responses of patients who underwent laparoscopic(LCR) and open resections(OCR) for colorectal cancer.</p> <p>Methods</p> <p>Between Mar 2009 and Sep 2009, 35 patients with colorectal carcinoma underwent LCR by laparoscopic surgeon. These patients were compared with 33 cases underwent conventional OCR by colorectal surgeon. Clinical data about the patients were collected prospectively. Comparison of the operative details and postoperative outcomes between laparoscopic and open resection was performed. Peripheral venous blood samples from these 68 patients were taken prior to surgery as well as on postoperative days(POD) 1, 4 and 7. Cell counts of total white blood cells, neutrophils, lymphocyte subpopulations, natural killer(NK) cells as well as CRP were determined by blood counting instrument, flow cytometry and hematology analyzer.</p> <p>Results</p> <p>There was no difference in the age, gender and tumor status between the two groups. The operating time was a little longer in the laparoscopic group (<it>P </it>> 0.05), but the blood loss was less (<it>P </it>= 0.039). Patients with laparoscopic resection had earlier return of bowel function and earlier resumption of diet as well as shorter median hospital stay (<it>P </it>< 0.001). Compared with OCR group, cell numbers of total lymphocytes, CD4⁺T cells and CD8⁺T cells were significant more in LCR group (<it>P </it>< 0.05) on POD 4, while there was no difference in the CD45RO⁺T or NK cell numbers between the two groups. Cellular immune responds were similar between the two groups on POD1 and POD7.</p> <p>Conclusions</p> <p>Laparoscopic colorectal resection gets less surgery stress and short-term advantages compared with open resection. Cellular immune respond appears to be less affected by laparoscopic colorectal resection when compared with open resection.</p

Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery

<p>Abstract</p> <p>Background</p> <p>Despite well-studied tumor hypoxia in laboratory, little is known about the association with other pathophysiological events in the clinical view. We investigated the prognostic value of hypoxia-inducible factor-1 alpha (HIF-1alpha) in hepatocellular carcinoma (HCC), and its correlations with inflammation, angiogenesis and MYC oncogene.</p> <p>Methods</p> <p>In a random series of 110 HCC patients, the mRNA of HIF-1alpha, inflammation related factors (COX-2, MMP7 and MMP9), angiogenesis related factors (VEGF and PDGFRA) and MYC in tumor tissue were detected by real-time RT-PCR and HIF-1alpha protein was assessed by immunohistochemistry. The correlations between HIF-1alpha mRNA and the factors mentioned previously, the relationship between HIF-1alpha and clinicopathologic features, and the prognostic value were analyzed.</p> <p>Results</p> <p>The expression of both HIF-1alpha mRNA and protein in HCC were independent prognostic factors for overall survival (OS) (<it>P </it>= 0.012 and <it>P </it>= 0.021, respectively) and disease-free survival (DFS) (<it>P </it>= 0.004 and <it>P </it>= 0.007, respectively) as well. Besides, the high expression of HIF-1alpha mRNA and protein proposed an advanced BCLC stage and more incidence of vascular invasion. The mRNA of HIF-1alpha had significantly positive correlations to that of COX-2, PDGFRA, MMP7, MMP9, MYC, except VEGF. In addition to HIF-1alpha, COX-2 and PDGFRA were also independent prognosticators for OS (<it>P </it>= 0.004 and <it>P </it>= 0.010, respectively) and DFS (<it>P </it>= 0.010 and <it>P </it>= 0.038, respectively).</p> <p>Conclusion</p> <p>HIF-1alpha in HCC plays an important role in predicting patient outcome. It may influence HCC biological behaviors and affect the tumor inflammation, angiogenesis and act in concert with the oncogene MYC. Attaching importance to HIF-1alpha in HCC may improve the prognostic and therapeutic technique.</p

Genome-Wide Screening for Genetic Alterations in Esophageal Cancer by aCGH Identifies 11q13 Amplification Oncogenes Associated with Nodal Metastasis

Esophageal squamous cell carcinoma (ESCC) is highly prevalent in China and other Asian countries, as a major cause of cancer-related mortality. ESCC displays complex chromosomal abnormalities, including multiple structural and numerical aberrations. Chromosomal abnormalities, such as recurrent amplifications and homozygous deletions, directly contribute to tumorigenesis through altering the expression of key oncogenes and tumor suppressor genes.To understand the role of genetic alterations in ESCC pathogenesis and identify critical amplification/deletion targets, we performed genome-wide 1-Mb array comparative genomic hybridization (aCGH) analysis for 10 commonly used ESCC cell lines. Recurrent chromosomal gains were frequently detected on 3q26-27, 5p15-14, 8p12, 8p22-24, 11q13, 13q21-31, 18p11 and 20q11-13, with frequent losses also found on 8p23-22, 11q22, 14q32 and 18q11-23. Gain of 11q13.3-13.4 was the most frequent alteration in ESCC. Within this region, CCND1 oncogene was identified with high level of amplification and overexpression in ESCC, while FGF19 and SHANK2 was also remarkably over-expressed. Moreover, a high concordance (91.5%) of gene amplification and protein overexpression of CCND1 was observed in primary ESCC tumors. CCND1 amplification/overexpression was also significantly correlated with the lymph node metastasis of ESCC.These findings suggest that genomic gain of 11q13 is the major mechanism contributing to the amplification. Novel oncogenes identified within the 11q13 amplicon including FGF19 and SHANK2 may play important roles in ESCC tumorigenesis

Targeting Cx43 and N-Cadherin, Which Are Abnormally Upregulated in Venous Leg Ulcers, Influences Migration, Adhesion and Activation of Rho GTPases

Venous leg ulcers can be very hard to heal and represent a significant medical need with no effective therapeutic treatment currently available