RNase L: Its Biological Roles and Regulation

2\u27-5\u27oligoadenylate-dependent ribonuclease L (RNase L) is one of the key enzymes involved in the function of interferons (IFNs), a family of cytokines participating in innate immunity against viruses and other microbial pathogens. Upon binding with its activator, 5\u27-phosphorylated, 2\u27-5\u27 linked oligoadenylates (2-5A), RNase L degrades single-stranded viral and cellular RNAs and thus plays an important role in the antiviral and antiproliferative functions of IFNs. In recent years, evidence has revealed that RNase L displays a broad range of biological roles which are summarized in this review

RNase L: Its Biological Roles and Regulation

2\u27-5\u27oligoadenylate-dependent ribonuclease L (RNase L) is one of the key enzymes involved in the function of interferons (IFNs), a family of cytokines participating in innate immunity against viruses and other microbial pathogens. Upon binding with its activator, 5\u27-phosphorylated, 2\u27-5\u27 linked oligoadenylates (2-5A), RNase L degrades single-stranded viral and cellular RNAs and thus plays an important role in the antiviral and antiproliferative functions of IFNs. In recent years, evidence has revealed that RNase L displays a broad range of biological roles which are summarized in this review

Tumour Suppressor Function of RNase L in A Mouse Model

RNase L is one of the key enzymes involved in the molecular mechanisms of interferon (IFN) actions. Upon binding with its activator, 5′-phosphorylated, 2′-5′ oligoadenylates (2-5A), RNase L plays an important role in the antiviral and anti-proliferative functions of IFN, and exerts proapoptotic activity independent of IFN. In this study, we have found that RNase L retards proliferation in an IFN-dependent and independent fashion. To directly measure the effect of RNase L on tumour growth in the absence of other IFN-induced proteins, human RNase L cDNA was stably expressed in P-57 cells, an aggressive mouse fibrosarcoma cell line. Three clonal cell lines were isolated in which the overexpression of RNase L was 15–20-fold of the endogenous level. Groups of five nude mice were injected subcutaneously with either the human RNase L overexpressing clones (P-RL) or control cells transfected with an empty vector (P-Vec). Tumour growth by the two cell lines was monitored by measuring tumour volumes. In the P-RL group, tumour formation was significantly delayed and the tumours grew much slower compared to the control group. Morphologically, the P-RL tumour appeared to have more polygonal cells and increased single cell tumour necrosis. Interestingly, P-RL tumours eventually started to grow. Further analysis revealed, however, that these tumours no longer expressed ectopic RNase L. Our findings suggest that RNase L plays a critical role in the inhibition of fibrosarcoma growth in nude mice

Comparison of Sterile and Clean Dressing Techniques in Post-operative Surgical Wound Infection in a Chinese Healthcare Facility

Purpose: To investigate the effect of sterile and clean dressing techniques on wound management in a Chinese hospital, and to compare their impact on wound healing and the cost of the dressing materials with respect to postoperative surgical wounds.Methods: A total of 130 patients, comprising 70 (53.8 %) males and 60 (46.2 %) females, who had undergone surgery in The Affiliated Hospital of Changchun Traditional Chinese Medicine University, Changchun, China in 2012 – 2014 were enrolled in the study. Of these, 65 (50 %) received sterile dressings and 65 (50 %) clean dressings. A control group comprising 25 patients, 15 (60 %) males and 10 (40 %) females, who attended the clinic for change dressings only, was also included. The patients’ dressings were changed four times daily with 2x sterile and 2x clean dressings. Details of all the changes, including the nutritional status of the patients, were recorded. The patients were followed-up up to the time of their discharge.Results: Twelve (18.5 %) patients out of those who received sterile or clean dressings were found to have acquired an infection. The size of the wounds was approximately 1.8 to 32.4 cm3 (mean: 5.2 ± 6.4 cm3) in size at the start of the study and 0.6 to 4.2 cm3 at the end of the study. A significant difference was identified between the sterile and clean dressing groups at the beginning of the study (U = 72.5; p < 0.12). A decrease in wound size was observed in both of these groups but was not statistically significant, while the change in wound volume, was significantly different (U = 84.5; p < 0.25). When the cost of the two dressing types was compared, the sterile items were more expensive than that of the clean items; thus, sterile dressing procedure was significantly more costly than clean dressing procedure (p < 0.01).Conclusion: With mounting concern regarding antimicrobial resistance and hospital-acquired infections, suitable wound dressing techniques are required to prevent infection and reduce the duration of wound healing after surgery without compromising patient safety.Keywords: Wound dressing, Postoperative, Antimicrobial resistance, Hospital acquired infection

Progressive decay of Ca2+ homeostasis in the development of diabetic cardiomyopathy

BACKGROUND: Cardiac dysfunction in diabetic cardiomyopathy may be associated with abnormal Ca(2+) homeostasis. This study investigated the effects of alterations in Ca(2+) homeostasis and sarcoplasmic reticulum Ca(2+)-associated proteins on cardiac function in the development of diabetic cardiomyopathy. METHODS: Sprague–Dawley rats were divided into 4 groups (n = 12, each): a control group, and streptozotocin-induced rat models of diabetes groups, examined after 4, 8, or 12 weeks. Evaluations on cardiac structure and function were performed by echocardiography and hemodynamic examinations, respectively. Cardiomyocytes were isolated and spontaneous Ca(2+) spark images were formed by introducing fluorescent dye Fluo-4 and obtained with confocal scanning microscopy. Expressions of Ca(2+)-associated proteins were assessed by Western blotting. RESULTS: Echocardiography and hemodynamic measurements revealed that cardiac dysfunction is associated with the progression of diabetes, which also correlated with a gradual but significant decline in Ca(2+) spark frequency (in the 4-, 8- and 12-week diabetic groups). However, Ca(2+) spark decay time constants increased significantly, relative to the control group. Expressions of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca(2+)-2ATPase (SERCA) and Na(+)/Ca(2+) exchanger (NCX1) were decreased, together with quantitative alterations in Ca(2+)regulatory proteins, FKBP12.6 and phospholamban progressively and respectively in the diabetic rats. CONCLUSIONS: Ca(2+) sparks exhibited a time-dependent decay with progression of diabetic cardiomyopathy, which may partly contribute to cardiac dysfunction. This abnormality may be attributable to alterations in the expressions of some Ca(2+)-associated proteins

Comparison of bicarbonate values from venous blood gas and chemistry panels measured at the time of diagnosis and resolution of diabetes ketoacidosis

Objective: To determine if bicarbonate values from venous blood gas (VBG) and plasma chemistry samples provided agreement in determining the bicarbonate criteria for the diagnosis and/or resolution of diabetic ketoacidosis (DKA). Methods: A retrospective chart review of data from patients admitted to a tertiary care hospital with a diagnosis of DKA over a four year period was performed. Paired bicarbonate values from a VBG and chemistry panel, if drawn within 60minutes of each other, were compared. Results: At the time of diagnosis of DKA, 197 paired bicarbonate values were available for analysis with the mean difference between the two methods of testing of 2.5mmol/L. 16 of the 197 (8%) paired values were discordant in meeting criteria for diagnosis of DKA. At the time of resolution of DKA, 83 paired bicarbonate samples were compared. The mean difference was 2.3mmol/L. 20 of the 83 (24%) paired bicarbonate values showed discordance with regards to meeting the bicarbonate criteria for resolution of DKA. Conclusion: Discordance between bicarbonate results from different analysis methods may lead to different determinations as to whether or not a patient meets the biochemical definition for diagnosis and resolution of DKA

Expanded CURB-65: A new score system predicts severity of community-acquired pneumonia with superior efficiency

Aim of this study was to develop a new simpler and more effective severity score for communityacquired pneumonia (CAP) patients. A total of 1640 consecutive hospitalized CAP patients in Second Affiliated Hospital of Zhejiang University were included. The effectiveness of different pneumonia severity scores to predict mortality was compared, and the performance of the new score was validated on an external cohort of 1164 patients with pneumonia admitted to a teaching hospital in Italy. Using age≥ 65 years, LDH>230u/L, albumin<3.5g/dL, platelet count<100×109/L, confusion, urea>7mmol/L, respiratory rate≥30/min, low blood pressure, we assembled a new severity score named as expanded-CURB-65. The 30-day mortality and length of stay were increased along with increased risk score. The AUCs in the prediction of 30-day mortality in the main cohort were 0.826 (95%CI, 0.807–0.844), 0.801 (95%CI, 0.781–0.820), 0.756 (95%CI, 0.735–0.777), 0.793 (95%CI, 0.773–0.813) and 0.759 (95%CI, 0.737–0.779) for the expanded-CURB-65, PSI, CURB-65, SMART-COP and A-DROP, respectively. The performance of this bedside score was confirmed in CAP patients of the validation cohort although calibration was not successful in patients with health care-associated pneumonia (HCAP). The expanded CURB-65 is objective, simpler and more accurate scoring system for evaluation of CAP severity, and the predictive efficiency was better than other score systems

Recombinant VP1, an Akt Inhibitor, Suppresses Progression of Hepatocellular Carcinoma by Inducing Apoptosis and Modulation of CCL2 Production

BACKGROUND: The application of viral elements in tumor therapy is one facet of cancer research. Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus has previously been demonstrated to induce apoptosis in cancer cell lines. Here, we aim to further investigate its apoptotic mechanism and possible anti-metastatic effect in murine models of hepatocellular carcinoma (HCC), one of the most common human cancers worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with rVP1 inhibited cell proliferation in two murine HCC cell lines, BNL and Hepa1-6, with IC₅₀ values in the range of 0.1-0.2 µM. rVP1 also induced apoptosis in these cells, which was mediated by Akt deactivation and dissociation of Ku70-Bax, and resulted in conformational changes and mitochondrial translocation of Bax, leading to the activation of caspases-9, -3 and -7. Treatment with 0.025 µM rVP1, which did not affect the viability of normal hepatocytes, suppressed cell migration and invasion via attenuating CCL2 production. The production of CCL2 was modulated by Akt-dependent NF-κB activation that was decreased after rVP1 treatment. The in vivo antitumor effects of rVP1 were assessed in both subcutaneous and orthotopic mouse models of HCC in immune-competent BALB/c mice. Intratumoral delivery of rVP1 inhibited subcutaneous tumor growth as a result of increased apoptosis. Intravenous administration of rVP1 in an orthotopic HCC model suppressed tumor growth, inhibited intra-hepatic metastasis, and prolonged survival. Furthermore, a decrease in the serum level of CCL2 was observed in rVP1-treated mice. CONCLUSIONS/SIGNIFICANCE: The data presented herein suggest that, via inhibiting Akt phosphorylation, rVP1 suppresses the growth, migration, and invasion of murine HCC cells by inducing apoptosis and attenuating CCL2 production both in vitro and in vivo. Recombinant protein VP1 thus has the potential to be developed as a new therapeutic agent for HCC

Love Postoperative ECG Shell (I)

Ongoing cutting-edge multidisciplinary research in textile fibers, biomedical sensors, and wireless and mobile telecommunications integrated with telemedicine, aims at developing intelligent biomedical clothing (IBC). This ECG shell design is a functional garment offering, health benefits, improved appearance and increased comfort. The garment is more comfortable because the high adhesive factor of current commercial hydrogel used in ECG monitoring causes patients skin allergies and pruritus from wearing the hydrogel for a long time

Love Postoperative ECG T-shirt (II)

This ECG T-shirt is a functional garment offering, health benefits, improved appearance and increased comfort. The garment is more comfortable because the high adhesive factor of current commercial hydrogel used in ECG monitoring causes patients skin allergies and pruritus from wearing the hydrogel for a long time. Additionally, since the sensors are attached to the lining of this two-layer raglan T-shirt, the exterior is smooth and makes the user tracking device inconspicuous