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The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C28-steroid with an unusual β- and γ-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC50 value of 2.61 ± 0.05 μmol·L-1. The β-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 μg·mL-1. Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 μg·mL-1, respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC50 values of 9.2 ± 0.03 and 13.3 ± 0.01 μmol·L-1, respectively.
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Humans , Acetylcholinesterase , Molecular Docking Simulation , Anti-Bacterial Agents , Glycosides , Lactones , PainABSTRACT
Objective To evaluate the role of silent information regulator 1 (SIRT1) signaling pathway in endotoxin-induced acute lung injury (ALI) in rats.Methods Ninety-six clean-grade healthy male Sprague-Dawley rats,aged 4 weeks,weighing 160-180 g,were divided into 4 groups (n=24 each) using a random number table method:control group (group C),ALI group,ALI + SIRT1 agonist SRT1720 group (group SRT),and ALI + SIRT1 inhibitor EX527 group (group EX).ALI was induced by injecting lipopolysaccharide (LPS) 5 mg/kg (diluted to 0.5 ml with 0.9％ normal saline) in ALI,SRT and EX groups.SRT1720 10 mg/kg was injected via the tail vein,and 30 min later ALI model was established in group SRT.EX527 1 μg/kg was injected via the tail vein,and 30 min later ALI model was established in group EX.Blood samples were collected from the abdominal aorta at 6,24 and 48 h after LPS injection for blood gas analysis,rats were then sacrificed and lungs were removed for determination of wet to dry weight ratio (W/D ratio) and expression of SIRT1,nuclear factor kappa B p65 (NF-κB p65),interleukin-6 (IL-6) and IL-1β protein and mRNA (by Western blot or real-time polymerase chain reaction) and for examination of pathological changes of lung tissues (with a light microscope).Results Compared with groups C,PaO2 was significantly decreased,and PaCO2 and W/D ratio were increased at each time point after LPS injection in ALI,SRT and EX groups,the expression of SIRT1 protein and mRNA was significantly down-regulated,and the expression of NF-κB p65,IL-6 and IL-1β protein and mRNA was upregulated at each time point after LPS injection in ALI and EX groups,and the expression of SIRT1,NFκB p65,IL-6 and IL-1β was significantly up-regulated at each time point after LPS injection in group SRT (P＜0.05).Compared with group ALI,PaO2 was significantly increased,PaCO2 and W/D ratio were decreased,the expression of SIRT1 protein and mRNA was up-regulated,the expression of NF-κB p65,IL-6 and IL-1β protein and mRNA was down-regulated at each time point after LPS injection (P＜0.05),and the pathological changes were significantly attenuated in group SRT,and no significant change was found in the parameters mentioned above at each time point after LPS injection in group EX (P＞0.05).Conclusion Inhibited SIRT1/NF-κB signaling pathway is involved in endotoxin-induced ALI in rats.
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<p><b>OBJECTIVE</b>To explore the role of silent information regulator 1 (SIRT1) signaling pathway in mediating the effect of dexmedetomidine (DEX) to alleviate postoperative cognitive dysfunction (POCD) in aged rats.</p><p><b>METHODS</b>Seventy-two healthy male Sprague-Dawley rats aged 18-20 months (weighing 500-700 g) were randomized equally into normal control group, POCD model group, DEX pretreatment group, and DEX and SIRT1 inhibitor (EX527) pretreatment group. In the latter 2 groups, DEX (25 μg/kg) was injected intraperitoneally in the rats 30 min before the operation, and normal saline was injected instead in the other 2 groups; in EX527 group, EX527 (1 μg/kg) was injected intravenously 5 min before the operation. In all but the control group, the rats were subjected to laparotomy lasting 30 min, and on days 1, 3, and 5 following the operation, 6 rats were randomly selected from each group for Morris water maze test to evaluate their cognitive functions. Immediately after the test, the rats were sacrificed and the hippocampus was collected for determination of the levels of tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) using ELISA; Western blotting was used to detect the expression of SIRT1 and nuclear factor- κB (NF-κB) in the hippocampal neurons.</p><p><b>RESULTS</b>Compared with the control rats, the rats in POCD group and EX527 group showed significantly prolonged escape latency, decreased frequency of crossing the original platform, increased TNF- and IL-6 levels, lowered SIRT1 expression in the hippocampal neurons, and increased NF-κB expression ( < 0.05), and these parameters were comparable between POCD group and EX527 group ( > 0.05). DEX pretreatment significantly alleviated cognitive dysfunction and attenuated the changes in TNF-, IL-6, SIRT1, and NF-κB expressions induced by the operation ( < 0.05), and EX527 pretreatment of the rats obviously blocked the effects of DEX ( < 0.05).</p><p><b>CONCLUSIONS</b>DEX alleviates POCD in aged rats probably via SIRT1 signaling pathway.</p>
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Objective To observe the diagnostic value of high-sensitivity C-reactive protein/albumin ratio (hs-CRP/ALB) in early-onset infection in premature and its clinical significance. Methods Clinical data of premature patients with high risk factors of intrauterine infection admitted to neonatal intensive care unit (NICU) of Liaocheng People's Hospital in Shandong Province from July 2013 to July 2015 were analyzed retrospectively. They were divided into infection and non-infection groups, as well as survival and death groups according to the outcome of the premature babies. The pre-albumin (PA), ALB, white blood cell count (WBC), platelet count (PLT), and hs-CRP at the moment of NICU admission (0 hour) and 24, 48 and 72 hours after NICU admission were compared. The receiver operating characteristic (ROC) curve was plotted for evaluation of the predictive value of serum hs-CRP/ALB ratio for the babies during hospitalization. Results A total of 214 cases of premature infants were enrolled, with 102 cases in infection group, and 112 in non-infection group. In infection neonates, 97 of them survived, and 5 died. ① The level of hs-CRP after NICU admission was increased in infection and non-infection groups, and it was significantly higher at 48 hours in infection group than that of the non-infection group [mg/L: 22.0 (7.6, 40.4) vs. 18.3 (12.9, 23.4),Z = 5.257, P = 0.038]. Then hs-CRP was decreased in non-infection, but it was persistently increased in infection group, and it was significantly higher at 72 hours in infection group than that of the non-infection group [mg/L: 25.5 (9.8, 43.5) vs. 12.2 (1.9, 22.1), Z = 5.879, P = 0.042]. The levels of ALB and WBC in infection group was significantly lower than those of the non-infection group [ALB (g/L): 27.9±2.7 vs. 29.1±2.9, t = 5.178, P = 0.026; WBC (×109/L): 13.7±7.1 vs. 16.1±7.9, t = 4.368, P = 0.037], and at 48 hours hs-CRP/ALB in infection group was significantly higher than that of non-infection group [0.16 (0.08, 0.57) vs. 0.07 (0.00, 0.23), Z = 3.436, P = 0.042]. There was no significant difference in PA and PLT between infection and non-infection groups. ② In premature patients with infection, ALB in non-survival group was decreased (g/L: 20.4±6.9 vs. 29.6±7.5, t = 7.859, P = 0.003), and 48-hour hs-CRP and hs-CRP/ALB ratio was significantly increased when compared with that of survival group [hs-CRP (mg/L): 25.8 (15.6, 54.8) vs. 18.2 (12.9, 36.2), Z = 4.067, P = 0.043; hs-CRP/ALB: 0.31 (0.28, 0.76) vs. 0.06 (0.00, 0.21), Z = 6.102, P = 0.011].③ It was shown by ROC curve analysis that the area under ROC curve (AUC) of 48-hour hs-CRP/ALB ratio for evaluating infection was 0.765, when the cut-off of 48-hour hs-CRP/ALB ratio was 0.08, the sensitivity was 84.2%, and the specificity was 76.3%. Conclusions The values of hs-CRP and ALB can be used as effective indexes in early diagnosis of intrauterine bacterial infection, and increase in 48-hour hs-CRP/ALB can improve the sensitivity of the diagnosis. Hs-CRP/ALB can be combined to guide rational use of antibiotics.
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Objective To study the value of serum albumin ( ALB ) level for the prognosis of late-preterm infants infection. Methods Late-preterm infants admitted to the neonatal intensive care unit ( NICU) from July 2012 to July 2013 were recruited and their clinical data retrospectively reviewed, including the laboratory examination results, neonatal critical illness scores ( NCIS ) , perinatal complications and prognosis. The infants were assigned into three groups based on ALB levels (＞30 g/L, 25-30 g/L, ＜25 g/L). Results A total of 257 cases were recruited and 122 cases (47. 4％) had ALB levels ＜25 g/L. 32 had neonatal sepsis ( sepsis group) , 190 neonatal infection ( infection group) and 35 without infection ( no-infection group ) . The incidences of hypoalbuminemia among these groups were 84. 4％, 50. 0％ and 28. 6％, with the mortality rate 15. 6％, 0. 5％ and 0％. The incidence of hypoalbuminemia and mortality rate in sepsis group were significantly higher than the other groups ( P＜0. 05 ) , and no statistically significant differences between infection group and no-infection group ( P＜0. 05). The ALB level in survived infants [(29. 6±7. 5)g/L] was statistically higher than the deceased ones [(20. 4±6. 9)g/L](P＜0. 05). The incidence of critically ill newborns was 65. 5％ in ALB ＜25 g/L group, significantly higher than the other groups (P＜0. 05). 26. 2％ in ALB ＜25 g/L group had more than 4 organs injuries, significantly higher than ALB ＞30 g/L group ( P＜0. 05 ) . Conclusions Hypoalbuminemia is common among neonates with sepsis. The ALB level had predictive value for the prognosis of neonatal infection.
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BACKGROUND:The umbilical cord blood is rich in hematopoietic stem/progenitor cel s that have strong proliferation and differentiation ability as wel as ability to form colonies, and exert important roles in stimulating bone marrow function, improving blood cel viability and quantity, promoting immune cel maturation, and maintaining immune balance. OBJECTIVE:To evaluate the clinical effects of autologous umbilical cord blood mononuclear cel transplantation on the immunologic function and prognosis for premature infants. METHODS:Sixty-two preterm infants who entered into NICU immediately after birth, weighing ≤ 1 500 g, were divided into treatment group and control group according to parent’s wil ingness. In the treatment group, the umbilical cord blood was extracted from the umbilical vein and re-infused into the preterm infants after density gradient centrifugation within 4 hours. The cel ular immunity levels, humoral immunity levels and clinical parameters were monitored before and after treatment. RESULTS AND CONCLUSION:After 1 week of treatment, the CD4, CD4/CD8 levels were significantly increased compared with the control group (P=0.01, 0.03), but CD8 level had no changes. At 1 week after treatment, IgM levels were both increased in the two groups, especial y in the control group (P=0.00);IgA levels had no changes;IgG levels were decreased, especial y in the control group (P=0.02). The incidence of severe infection during hospitalization was 13%in the treatment group, which was lower than the control group (16%), but there was no difference between the two groups. The proportion of infants undergoing mechanical ventilation and average length of stay had significant differences between the two groups (P<0.05). After 12 months, the incidence of recurrent respiratory tract infections was zero in the treatment group and one case in the control group, and there was a significant difference between the two groups. These findings indicate that autologous umbilical cord blood mononuclear cel transplantation can improve the immunologic function, slower the reduction of IgG levels, reduce the usage of breathing machine, shorten the length of stay, and reduce the incidence of recurrent respiratory tract infections in preterm infants.
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Objective To investigate the clinical features,treatment and the causes of death in severe infectious disease complicated with capillary leak syndrome(CLS)in neonates.Methods The clinical data,laboratory finding,treatmand clinical outcome of 11 neonates who had severe infectious disease complicated with CLS in our NICU from Jan 2009 to Jul 2010 were collected and analysed retrospectively.Results Among the 11neonates,five had pneumonia and the other six had sepsis.All the 11 cases appeared progressive edema on skin and mucosa,dyspnoea,infective shock,oliguria and hypoalbuminemia(10～20 g/L).We treated the 11cases with hydroxyethyl starch(10～15 ml/kg,every 8 to 12 h)at early stage on the basis of infection control,anti-shock treatment,mechanical ventilation,symptomatic treatment and a stable internal environment.At last,6 cases were rescued,in whom 4 cases were well-developed,had normal intelligence and athletic ability,the other two cases had hydrocephalus or muscle tone high of both lower extremities.Five cases died.Conelusion CLS is a severe complication of neonatal severe infection,and had high mortality.Treating with hydroxvethvl starch at an early stage can increase the survival rate.