The interaction between XBP1 and eNOS contributes to endothelial cell migration

Trabalho final de mestrado integrado em Medicina área científica de Urologia, apresentado á Faculdade de Medicina da Universidade de CoimbraINTRODUÇÃO: Nas últimas décadas a nefrectomia parcial tem assumido um papel de destaque no tratamento do carcinoma de células renais. Esta técnica, também denominada cirurgia poupadora de nefrónios, permite remover o tumor na totalidade, preservando o parênquima renal adjacente. As suas indicações tornaram-se mais abrangentes à medida que os resultados se mostraram cada vez mais promissores. Assim, actualmente a nefrectomia parcial é o tratamento padrão do carcinoma de células renais, em detrimento da tradicional nefrectomia radical. Discute-se agora qual das duas, nefrectomia parcial aberta ou laparoscópica, é a melhor opção. OBJECTIVOS: Rever as evidências científicas relativas ao tratamento do carcinoma de células renais pela nefrectomia parcial, aberta e laparoscópica, definindo o papel actual de cada uma delas nesta área. MÉTODOS: Pesquisa na PubMed e Medline de artigos relativos a nefrectomia radical e nefrectomia parcial aberta e laparoscópica, publicados entre 1997 e 2009. Consulta das “Guidelines” da Associação Europeia de Urologia. DESENVOLVIMENTO: A nefrectomia parcial mostra resultados oncológicos semelhantes aos da nefrectomia radical, permitindo uma menor morbilidade renal a longo prazo. A nefrectomia parcial aberta é agora o tratamento recomendado pelas “Guidelines” da Associação Europeia de Urologia para o tratamento de tumores com diâmetro inferior a 4 cm, limitados ao rim, mesmo quando o rim contralateral é normal. As indicações poderão ainda ser alargadas para tumores até 7 cm de diâmetro, dependendo das características do tumor. A nefrectomia parcial laparoscópica, embora tecnicamente mais exigente, é uma boa opção de tratamento em centros com experiência na realização da técnica, revelando bons resultados a curto prazo. CONCLUSÕES: A nefrectomia parcial aberta é actualmente o tratamento padrão do carcinoma de células renais. A nefrectomia parcial laparoscópica revela resultados a curto prazo semelhantes aos da nefrectomia parcial aberta, contudo são necessários estudos confirmando esses resultados a longo prazoINTRODUCTION: In the last decades partial nephrectomy have had an important role in the treatment of renal cell carcinoma. This surgery, also known as nephron-sparing surgery, allows to remove the tumor and to preserve the surrounding healthy renal parenchyma. Moreover, with the evolution of the technique its indications got more comprehensive. So, nowadays, partial nephrectomy is the standard treatment for renal cell carcinoma, instead of the traditional radical nephrectomy. There is now a discussion between which of the two, open or laparoscopic partial nephrectomy, is the best option. OBJECTIVES: Review the scientific evidences related to the treatment of renal cell carcinoma through open and laparoscopic partial nephrectomy, defining the actual role of both in this area. METHODS: Research articles related to radical nephrectomy, open and laparoscopic partial nephrectomies at PubMed and Medline publications between 1997 and 2009. Consult of the Guidelines of European Urology Association. DEVELOPMENT: Partial nephrectomy shows oncological outcomes similar to those of radical nephrectomy with less renal morbidity at long-term follow-up. Open partial nephrectomy is now the recommended treatment by the Guidelines of European Urology Association for the treatment of tumors less than 4 cm, limited to the kidney, even when the other kidney is normal. Indications can also include tumors less than 7 cm, depending on the characteristics of the tumor. Laparoscopic partial nephrectomy, although technically more demanding, is a good option in specialized centers and reveals similar results in a short-term. CONCLUSIONS: Nowadays open partial nephrectomy is the standard treatment of renal cell carcinoma. Laparoscopic partial shows similar results as open surgery in a short-term, however, more studies are needed to confirm this results at long-term. Key-words: Open partial nephrectomy, laparoscopic partial nephrectomy, renal cell carcinoma, indications, results

Diet-derived circulating antioxidants and risk of inflammatory bowel disease: a Mendelian randomization study and meta-analysis

BackgroundPrevious studies have shown conflicting results regarding the impact of circulating antioxidants on the risk of inflammatory bowel disease (IBD). In this study, our intent was to investigate the causal relationship between circulating antioxidants and IBD using Mendelian randomization (MR).MethodsInstrumental variables for absolute circulating antioxidants (ascorbate, retinol, lycopene, and β-carotene) and circulating antioxidant metabolites (α-tocopherol, γ-tocopherol, ascorbate, and retinol) were screened from published studies. We obtained outcome data from two genome-wide association study (GWAS) databases, including the international inflammatory bowel disease genetics consortium (IIBDGC, 14,927 controls and 5,956 cases for Crohn’s disease (CD), 20,464 controls and 6,968 cases for ulcerative colitis (UC), and 21,770 controls and 12,882 cases for IBD) and the FinnGen study (375,445 controls and 1,665 cases for CD, 371,530 controls and 5,034 cases for UC, and 369,652 controls and 7,625 cases for IBD). MR analysis was performed in each of the two databases and those results were pooled using meta-analysis to assess the overall effect of exposure on each phenotype. In order to confirm the strength of the findings, we additionally conducted a replication analysis using the UK Biobank.ResultsIn the meta-analysis of the IIBDGC and FinnGen, we found that each unit increase in absolute circulating level of retinol was associated with a 72% reduction in the risk of UC (OR: 0.28, 95% CI: 0.10 to 0.78, P=0.015). The UC GWAS data from the UK Biobank also confirmed this causal relationship (OR: 0.99, 95% CI: 0.97 to 1.00, P=0.016). In addition, there was suggestive evidence that absolute retinol level was negatively associated with IBD (OR: 0.41, 95% CI: 0.18 to 0.92, P=0.031). No other causal relationship was found.ConclusionOur results provide strong evidence that the absolute circulating level of retinol is associated with a reduction in the risk of UC. Further MR studies with more instrumental variables on circulating antioxidants, especially absolute circulating antioxidants, are needed to confirm our results

Methanol extract of Inonotus obliquus improves type 2 diabetes mellitus through modifying intestinal flora

Type 2 diabetes mellitus (T2DM) poses a significant risk to human health. Previous research demonstrated that Inonotus obliquus possesses good hypolipidemic, anti-inflammatory, and anti-tumor properties. In this research, we aim to investigate the potential treatment outcomes of Inonotus obliquus for T2DM and discuss its favourable influences on the intestinal flora. The chemical composition of Inonotus obliquus methanol extracts (IO) was analyzed by ultra-high-performance liquid chromatography-Q extractive-mass spectrometry. IO significantly improved the blood glucose level, blood lipid level, and inflammatory factor level in T2DM mice, and effectively alleviated the morphological changes of colon, liver and renal. Acetic acid, propionic acid, and butyric acid levels in the feces of the IO group were restored. 16S rRNA gene sequencing revealed that the intestinal flora composition of mice in the IO group was significantly modulated. Inonotus obliquus showed significant hypoglycemic and hypolipidemic effects with evident anti-inflammatory activity and improved the morphological structure of various organs and cells. Inonotus obliquus increased the levels of short-chain fatty acids in the environment by increasing the population of certain bacteria that produce acid, such as Alistipes and Akkermansia, which are beneficial to improve intestinal flora disorders and maintain intestinal flora homeostasis. Meanwhile, Inonotus obliquus further alleviated T2DM symptoms in db/db mice by down-regulating the high number of microorganisms that are dangerous, such as Proteobacteria and Rikenellaceae_RC9_gut_group and up-regulating the abundance of beneficial bacteria such as Odoribacter and Rikenella. Therefore, this study provides a new perspective for the treatment of T2DM by demonstrating that drug and food homologous active substances could relieve inflammation via regulating intestinal flora

Activation of synovial fibroblasts from patients at revision of their metal-on-metal total hip arthroplasty

BACKGROUND: The toxicity of released metallic particles generated in metal-on-metal (MoM) total hip arthroplasty (THA) using cobalt chromium (CoCr) has raised concerns regarding their safety amongst both surgeons and the public. Soft tissue changes such as pseudotumours and metallosis have been widely observed following the use of these implants, which release metallic by-products due to both wear and corrosion. Although activated fibroblasts, the dominant cell type in soft tissues, have been linked to many diseases, the role of synovial fibroblasts in the adverse reactions caused by CoCr implants remains unknown. To investigate the influence of implants manufactured from CoCr, the periprosthetic synovial tissues and synovial fibroblasts from patients with failed MoM THA, undergoing a revision operation, were analysed and compared with samples from patients undergoing a primary hip replacement, in order to elucidate histological and cellular changes. RESULTS: Periprosthetic tissue from patients with MoM implants was characterized by marked fibrotic changes, notably an increase in collagen content from less than 20% to 45-55%, an increase in α-smooth muscle actin positive cells from 4 to 9% as well as immune cells infiltration. Primary cell culture results demonstrated that MoM synovial fibroblasts have a decreased apoptosis rate from 14 to 6% compared to control synovial fibroblasts. In addition, synovial fibroblasts from MoM patients retained higher contractility and increased responsiveness to chemotaxis in matrix contraction. Their mechanical properties at a single cell level increased as observed by a 60% increase in contraction force and higher cell stiffness (3.3 kPa in MoM vs 2.18 kPa in control), as measured by traction force microscopy and atomic force microscopy. Further, fibroblasts from MoM patients promoted immune cell invasion by secreting monocyte chemoattractant protein 1 (MCP-1, CCL2) and induced monocyte differentiation, which could also be associated with excess accumulation of synovial macrophages. CONCLUSION: Synovial fibroblasts exposed in vivo to MoM THA implants that release CoCr wear debris displayed dramatic phenotypic alteration and functional changes. These findings unravelled an unexpected effect of the CoCr alloy and demonstrated an important role of synovial fibroblasts in the undesired tissue reactions caused by MoM THAs

Echinococcus multilocularis and Echinococcus shiquicus in a small mammal community on the eastern Tibetan Plateau : host species composition, molecular prevalence, and epidemiological implications

Background The eastern part of the Tibetan Plateau is now recognized as an endemic region with the highest reported human infection rates in the world of human alveolar echinococcosis (AE) caused by Echinococcus multilocularis. Existing epidemiological studies on AE have mainly focused on the synanthropic environment, while basic parasitological and ecological aspects in wildlife host species remain largely unknown, especially for small mammal hosts. Therefore, we examined small mammal host species composition, occurrence, and the prevalence of both E. multilocularis and E. shiquicus in Shiqu County (Sichuan Province, China), eastern Tibetan Plateau. Results In total, 346 small mammals from five rodent and one pika species were trapped from four randomly set 0.25 ha square plots. Two vole species, Lasiopodomys fuscus (n = 144) and Microtus limnophilus (n = 44), and the plateau pika (Ochotona curzoniae) (n = 135), were the three most-dominant species trapped. Although protoscoleces of E. multilocularis and E. shiquicus were only observed in L. fuscus and O. curzoniae, respectively, cox1 and nad1 gene DNA of E. shiquicus was detected in all the small mammal species except for Neodon irene, whereas E. multilocularis was detected in the three most-dominant species. The overall molecular prevalence of Echinococcus species was 5.8 (95% CI: 3.3–8.2%) ~ 10.7% (95% CI: 7.4–14.0%) (the conservative prevalence to the maximum prevalence with 95% CI in parentheses), whereas for E. multilocularis it was 4.3 (95% CI: 2.2–6.5%) ~ 6.7% (95% CI: 4.0–9.3%), and 1.5 (95% CI: 0.2–2.7%) ~ 4.1% (95% CI: 2.0–6.1%) for E. shiquicus. The prevalence of both E. multilocularis and E. shiquicus, was significantly higher in rodents (mainly voles) than in pikas. Phylogenetic analyses revealed that Echinococcus haplotypes of cox1 from small mammal hosts were actively involved in the sylvatic and anthropogenic transmission cycles of E. multilocularis in the eastern Tibetan Plateau. Conclusions In contrast to previous studies, the current results indicated that rodent species, rather than pikas, are probably more important natural intermediate hosts of E. multilocularis and E. shiquicus in the eastern Tibetan Plateau. Thus, understanding interspecific dynamics between rodents and pikas is essential to studies of the echinococcosis transmission mechanism and human echinococcosis prevention in local communities. Keywords: Echinococcus multilocularis, E. shiquicus, Small mammal Prevalence, Tibetan Platea

Cobalt (II) ions and nanoparticles induce macrophage retention by ROS-mediated down-regulation of RhoA expression

The authors are grateful to the China Scholarship Council (CSC) for the support of Jing Xu

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data