[Bacterial Meningitis as well as Suppurative Thrombophlebitis right after Induce Position Shots: In a situation Report].
  RESULTS Of 1486 enrolled patients, 637 (43%) of patients harbored high-risk endoscopic stigmata according to international consensus statements. The area under the receiver-operating characteristic curve (AUC) for the HARBINGER was 0.76 (95% confidence interval [CI], 0.72-0.79), which was significantly superior both to the GBS (AUC, 0.68; 95% CI, 0.64-0.71; p less then 0.001) and to the AIMS65 (AUC, 0.54; 95% CI, 0.50-0.58; p less then 0.001). When the HARBINGER cut-off value was set at 1 to rule out patients who needed admission and urgent endoscopy, its sensitivity and specificity was 98.8% (95% CI, 97.9-99.6) and 15.5% (95% CI, 13.1-18.0), respectively. CONCLUSION The HARBINGER, a simple 3-variable score, provides a more accurate method for triage of patients with suspected UGIB than both the GBS and the AIMS65. AIMS The activation of hepatic stellate cells (HSCs) plays a central role in liver fibrosis progression. Phospholipase D (PLD) enzymes participate in multiple cellular activities. However, whether and how PLD regulates HSCs activation remain elusive. MAIN METHODS The expression of intrahepatic PLD1 and PLD2 was determined in CCl4-induced mouse liver fibrosis models by western blot and immunohistochemistry. Cell model of liver fibrogenesis was constructed using rat HSCs line (HSC-T6) treated with recombinant transforming growth factor β1 (TGFβ1). Fibrogenesis was evaluated on the aspects of proliferation, expression of pro-fibrogenic markers and migration. The effects mediated by PLD1-mTOR axis on TGFβ1-induced fibrogenesis were evaluated using HSC-T6 treated with small-molecular PLD1 inhibitors, PLD1-SiRNA, rapamycin (mTOR inhibitor) and MHY1485 (mTOR activator). KEY FINDINGS Significant increase of PLD1, not PLD2 was documented in CCl4-induced cirrhotic compared to normal liver tissues. Suppression of PLD1 activities by PLD inhibitors or down-regulation of PLD1 expression in HSC-T6 could significantly restrain TGFβ1-induced fibrogenesis, as reflected by decreased cell proliferation and reduced expression of pro-fibrogenic markers. Besides, either PLD1 inhibitor or PLD1-SiRNA significantly inhibited mTOR activity of HSC-T6. Moreover, PLD1 inhibitors not only exhibited similar effects with rapamycin in TGFβ1-induced fibrogenesis, but also blunted MHY1485 enhanced cell proliferation of HSC-T6. SIGNIFICANCE The PLD1-mTOR axis of HSCs could be therapeutically targeted in advanced liver fibrosis. AIMS The objective of this study was to establish a more accurate analytical model and method for grip strength test of mice and to investigate the beneficial effects of lifelong exercise training to prevent functional decline of muscle during aging. MAIN METHODS Fifty randomly selected adult male BALB/c mice (24-56 week age) were used in grip strength testing periodically with short periods (3 s). Such method was used to detect a modified grip strength test. Then sixty-four male BALB/c mice (6 week age) were assigned into groups Sedentary (n = 32), Exercise (n = 32, lifelong treadmill training 3 days per week and 30 min per day). The muscle strength and morphology parameters were measured at the ages of 6, 12, 30 and 64 weeks, respectively. KEY FINDINGS The grip strength (peak value and endurance) of sedentary group monotonically decreased in adult BALB/c mice during aging, while that of exercise group remained a relatively high level even slightly increased at aged period. Meanwhile, lifelong exercise training could slow down the loss of gastrocnemius muscle mass, myofiber cross-sectional area, myonuclear number and myonuclear domain. The number of myofibers was relatively stable in adult mice. SIGNIFICANCE Modified analytical method for grip strength testing, with improved accuracy and reliability, may be an efficient substitute for conventional method in measuring the strength and endurance of mice and investigating the effect of lifelong exercise on muscle loss.  https://www.selleckchem.com/products/favipiravir-t-705.html  Lifelong exercise training helps prevent muscle loss and muscle defunctionalization while aging. BACKGROUND Arsenic trioxide (ATO) can bind directly to the human promyelocytic leukemia (PML) protein, leading to modification of PML by SUMOs. UBC9 is the only known E2-conjugating enzyme involved in SUMOylation. PML degradation via RNF4, an E3 ubiquitin ligases family member.  https://www.selleckchem.com/products/favipiravir-t-705.html  PML is key organizer of nuclear bodies (NBs) that regulate many biological processes such as senescence, and DNA damage. ATO can activate the TGFβ/Smad signaling pathway, causing liver fibrosis. However, the roles of PML Sumoylation in ATO-induced liver fibrosis remain unclear. OBJECTIVE This study aimed to investigate the role of PML Sumoylation in the ATO-induced HSCs activation and to improve the mechanism of ATO-induced liver fibrosis. METHODS Hepatic stellate cells (HSCs) were treated with 2 μmol/L ATO. Cell viability was detected by CCK-8 analysis. Immunoblot analysis and real-time quantitative PCR were used to detect the expression of IL-1β, TNF-α, TGF-β1, p-Smad2/3, α-SMA, Collagen I and PML SUMOylation after silencing PML, UBC9, and RNF4, respectively. The formation of PML-NBs was observed by immunofluorescence staining. RESULTS 2 and 5 μmol/L ATO intervention increased HSCs cell viability. ATO was able to significantly trigger PML SUMOylation and the formation of PML-NBs. Inhibition of SUMOylated PML by silencing UBC9, subsequently preventing the downregulation of HSCs activation indicators induced by ATO (P  less then  0.05). Conversely, enhancing SUMOylated PML accumulation by silencing RNF4, activating TGFβ/Smad signaling pathway, eventually promoting the induction of liver fibrosis. CONCLUSION These results indicated that PML SUMOylation plays a critical role in the development of liver fibrosis induced by ATO. AIMS β-Estradiol (β-E), one of the chemical forms of female gonad hormone exhibited antioxidant efficacy in biochemical system, in vitro. The aim of the study was to investigate whether any other mechanism of protection by β-E to hepatic mitochondria in presence of stressor agent i.e.,a combination of Cu2+ and ascorbic acid is involved. MAIN METHODS Freshly prepared goat liver mitochondria was incubated with stressors and 1 μM β-E and post incubated with the same concentration at 37 °C at pH 7.4. Mitochondrial viability, biomarkers of oxidative stress, activities of Krebs cycle enzymes, mitochondrial membrane potential, Ca2+ permeability were measured. Mitochondrial morphology and binding pattern of β-E with stressors were also studied. KEY FINDINGS Upon incubation of mitochondria with Cu, ascorbic acid and their combination there is a significant decline in activities of four of Krebs cycle enzymes in an uncompetitive manner with a concomitant increase in Ca2+ permeability and membrane potential of inner mitochondrial membrane, which is withdrawn during co-incubation with β-E, but was not reversed during post incubation with the β-E.