Effluent Markers Related to Epithelial Mesenchymal Transition with Adjusted Values for Effluent Cancer Antigen 125 in Peritoneal Dialysis Patients

Objectives. Epithelial mesenchymal transition (EMT) is important for peritoneal deterioration. We evaluated the association between peritoneal solute transport rate (PSTR) and effluent markers related to EMT with adjusted values for effluent cancer antigen 125 (CA125). Methods. One hundred five incident peritoneal dialysis (PD) patients on PD for 25 (12–68) months with biocompatible solutions were included in the study. Fast peritoneal equilibration test was used to evaluate PSTR. Effluent hepatocyte growth factor (HGF), bone morphogenic protein-7 (BMP-7), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and CA125 at 4 h were measured. Results. Patients with dialysate/plasma creatinine ≧0.82 showed significantly higher effluent HGF (240 versus 133 pg/mL, P < .001), VEGF, IL-6, and IL6/CA125 levels than the others but no significant differences in effluent HGF/CA125, BMP-7, and BMP7/CA125 were observed. Conclusion. Increase in the effluent HGF levels as a compensatory mechanism is a marker of peritoneal deterioration, but controversy remains regarding adjusted value for CA125

CRISPR Inhibition of Prophage Acquisition in Streptococcus pyogenes

Streptococcus pyogenes, one of the major human pathogens, is a unique species since it has acquired diverse strain-specific virulence properties mainly through the acquisition of streptococcal prophages. In addition, S. pyogenes possesses clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems that can restrict horizontal gene transfer (HGT) including phage insertion. Therefore, it was of interest to examine the relationship between CRISPR and acquisition of prophages in S. pyogenes. Although two distinct CRISPR loci were found in S. pyogenes, some strains lacked CRISPR and these strains possess significantly more prophages than CRISPR harboring strains. We also found that the number of spacers of S. pyogenes CRISPR was less than for other streptococci. The demonstrated spacer contents, however, suggested that the CRISPR appear to limit phage insertions. In addition, we found a significant inverse correlation between the number of spacers and prophages in S. pyogenes. It was therefore suggested that S. pyogenes CRISPR have permitted phage insertion by lacking its own spacers. Interestingly, in two closely related S. pyogenes strains (SSI-1 and MGAS315), CRISPR activity appeared to be impaired following the insertion of phage genomes into the repeat sequences. Detailed analysis of this prophage insertion site suggested that MGAS315 is the ancestral strain of SSI-1. As a result of analysis of 35 additional streptococcal genomes, it was suggested that the influences of the CRISPR on the phage insertion vary among species even within the same genus. Our results suggested that limitations in CRISPR content could explain the characteristic acquisition of prophages and might contribute to strain-specific pathogenesis in S. pyogenes

Кераміка «terra sigillata» з с. Зимне на Волині

Стаття присвячена публікації чотирьох керамічних посудин типу «terra sigillata», знайдених на дні р. Луги у с. Зимне Володимир-Волинського району Волинської області. Попередній аналіз цих знахідок дозволяє віднести їх до Понтійського центру виробництва такого посуду. Вірогідним шляхом потрапляння цієї колекції на Волинь була готська експансія у Північне Причорномор’я

Dimerization of sortilin regulates its trafficking to extracellular vesicles

Extracellular vesicles (EVs) play a critical role in intercellular communication by transferring microRNAs, lipids, and proteins to neighboring cells. Sortilin, a sorting receptor that directs target proteins to the secretory or endocytic compartments of cells, is found in both EVs and cells. In many human diseases, including cancer and cardiovascular disorders, sortilin expression levels are atypically high. To elucidate the relationship between cardiovascular disease, particularly vascular calcification, and sortilin expression levels, we explored the trafficking of sortilin in both the intracellular and extracellular milieu. We previously demonstrated that sortilin promotes vascular calcification via its trafficking of tissue-nonspecific alkaline phosphatase to EVs. Although recent reports have noted that sortilin is regulated by multiple post-translational modifications, the precise mechanisms of sortilin trafficking still need to be determined. Here, we show that sortilin forms homodimers with an intermolecular disulfide bond at the cysteine 783 (Cys783) residue, and because Cys783 can be palmitoylated, it could be shared via palmitoylation and an intermolecular disulfide bond. Formation of this intermolecular disulfide bond leads to trafficking of sortilin to EVs by preventing palmitoylation, which further promotes sortilin trafficking to the Golgi apparatus. Moreover, we found that sortilin-derived propeptide decreased sortilin homodimers within EVs. In conclusion, sortilin is transported to EVs via the formation of homodimers with an intermolecular disulfide bond, which is endogenously regulated by its own propeptide. Therefore, we propose that inhibiting dimerization of sortilin acts as a new therapeutic strategy for the treatment of EV-associated diseases, including vascular calcification and cancer

Relationship between blood pressure and body composition in chronic kidney disease patients: dry mass index and ratio of total body water to estimate total body water

Obesity and hypervolemic status are mainly one of causes of hypertension in chronic kidney disease (CKD) patients. However, it is difficult to assess these factors because changes in body weight (BW) in CKD patients are affected not only by muscle and fat, but also by fluid status. The objective of this study is to assess the relationship between blood pressure (BP) and body composition using dry mass index (DMI), which subtracts total body water (TBWBIA) from BW, and a ratio of TBWBIA to estimated TBWwatson by anthropometric formula (Watson). In 40 randomly selected CKD patients, body composition and BP measured by bioelectrical impedance analysis (BIA) and by 24 hour ambulatory BP monitoring, respectively. Based on DMI and TBWBIA/TBWwatson ratio, participants were categorized into 3 of obese, 15 of overweight, 21 of optimal weight, and one of underweight, or into 13 with hypovolemia, 19 with euvolemia, and 8 hypervolemia. DMI TBWBIA/TBWwatson r p r p Daytime sBP -0.005 0.998 0.429 0.006 Night-time sBP -0.086 0.588 0.534 <0.001 Non-dipping status 0.095 0.558 0.413 <0.001 Ambulatory BP was associated with the ratio of TBWBIA to TBWwatson. In conclusion, the ratio of TBWBIA to TBWwatson is a reliable marker of fluid status, which is of practical use to assess cause of hypertension in CKD patients

External Beam Radiotherapy for Focal Lymphoepithelioma-Like Carcinoma in the Urinary Bladder: A Case Report and Literature Review

Lymphoepithelioma is a malignant epithelial tumor in the nasopharynx characterized by prominent lymphoid infiltration. Carcinomas that resemble lymphoepitheliomas have been called lymphoepithelioma-like carcinomas and have been reported in other organs. A tumor in the bladder is categorized by the percentage of the total area occupied by the lymphoepithelioma-like carcinoma pattern, with the prognosis dependent on the percentage. We present an 81-year-old man with stage 3 chronic obstructive pulmonary disease and a history of aortic aneurysm repair. The computed tomography scans indicated thickening and irregularity of the bladder wall, with left external iliac lymph node metastasis. His diagnosis was bladder cancer, and the clinical stage was evaluated as T3N1M0. Transurethral resection of the bladder tumor was performed, and the pathological specimen showed that the tumor was composed of undifferentiated malignant cells with sheets and nests arranged in a syncytial pattern, as well as an urothelial carcinoma lesion. A prominent lymphoid reaction accompanied the tumor. The pathological diagnosis was focal-type lymphoepithelioma-like carcinoma containing a component of urothelial carcinoma G3>G2. His general condition was such that he could not tolerate radical cystectomy or systemic chemotherapy. External beam radiotherapy (total 60 Gy) was given to the bladder, including the lymph node metastatic lesion. No cancer recurrence was detected by regular follow-up computed tomography and cystoscopy. He eventually died of other causes 48 months later. Although treatment for focal lymphoepithelioma-like carcinoma generally requires multifocal therapies, in the present case, the bladder became tumor free. We also summarize previously reported lymphoepithelioma-like carcinoma cases treated with radiotherapy

Stepwise Introduction of Different Substituents to α-Chloro-ω-hydrooligosilanes: Convenient Synthesis of Unsymmetrically Substituted Oligosilanes

A series of unsymmetrically substituted oligosilanes were synthesized via stepwise introduction of different substituents to &alpha;-chloro-&omega;-hydrooligosilanes. The reactions of &alpha;-chloro-&omega;-hydrooligosilanes with organolithium or Grignard reagents gave hydrooligosilanes having various alkyl, alkenyl, alkynyl and aryl groups. Thus-obtained hydrooligosilanes were converted into alkoxyoligosilanes by ruthenium-catalyzed dehydrogenative alkoxylation with alcohols