ABSTRACT
Background: Testosterone deficiency is reportedly correlated with an elevation of cholesterol in plasma, but the mechanism remains unclear. Our objective was to investigate the effects of testosterone deficiency on cholesterol metabolism and the corresponding molecular changes in vivo and in vitro. Methods: SD rats were randomized into three groups: sham-operated (SHAM), subtotal orchiectomized (SO), and orchiectomized (ORX) and fed for 8 weeks. HepG2 cells were cultured with medium containing testosterone with the final concentrations of 0, 10, 30, and 300 nM. Method of isotope tracing and fluorescence labelling was adopted to investigate cholesterol metabolism. Several key molecules of cholesterol metabolism were also analyzed. Results: SO and ORX rats displayed dysfunctional liver uptake of cholesterol. HepG2 cells incubated with testosterone of lower and excessive level exhibited reduced capacity of cholesterol uptake. Further investigation revealed that lack of testosterone induced increased proprotein convertase subtilisin/kexin type 9 (PCSK9) and decreased low-density lipoprotein receptor (LDLR) both in vivo and in vitro. Moreover, the androgen receptor (AR) antagonist flutamide mimicked the effects of testosterone deficiency on PCSK9 and LDLR indicating the role of AR as a mediator in triggering attenuating liver cholesterol uptake in which testosterone instead of dihydrotestosterone (DHT) is the major functional form of androgen. Conclusion: Testosterone deficiency attenuated cholesterol liver uptake mediated by the PCSK9-LDLR pathway, in which AR and testosterone without transforming to DHT play important roles.
ABSTRACT
Pentraxin 3 (PTX3) is a soluble pattern recognition receptor (PRR), which is produced by severalkinds of cells, such as neutrophils, dendritic cells, macrophages, and epithelial cells.PTX3 is known to play an important protective effect against Aspergillus. Genetic linkage ingene-targeted mice and human PTX3 plays a non-redundant role in the immune protectionagainst specific pathogens, especially Aspergillus. Recent studies have shown that the polymorphismof PTX3 is associated with increased susceptibility to invasive aspergillosis (IA). Inthis review, we provide an overview of these studies that underline the potential of PTX3 indiagnosis and therapy of IA.
ABSTRACT
Pentraxin 3 (PTX3) is a soluble pattern recognition receptor (PRR), which is produced by severalkinds of cells, such as neutrophils, dendritic cells, macrophages, and epithelial cells.PTX3 is known to play an important protective effect against Aspergillus. Genetic linkage ingene-targeted mice and human PTX3 plays a non-redundant role in the immune protectionagainst specific pathogens, especially Aspergillus. Recent studies have shown that the polymorphismof PTX3 is associated with increased susceptibility to invasive aspergillosis (IA). Inthis review, we provide an overview of these studies that underline the potential of PTX3 indiagnosis and therapy of IA.
ABSTRACT
Objective To investigate the potential role of soluble triggering receptor expressed on ayeloid cells-1(sTREM-1) expression in serum,endotracheal aspiration (ETA),bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC) as early biomarkers for the diagnosis of ventilator-associated pneumonia (VAP) in patients with acute ischemic stroke.Methods One hundred and thirty-two patients with clinically suspected VAP were prospectively included in this multicenter study.The levels of sTREM-1 in serum,ETA,BALF and EBC were analyzed for diagnostic evaluation at the time of VAP clinically suspected.The bacterial count over 104/CFU as a gold standard for VAP,and the receiver operating characteristic curves were used to identify the ideal cutoff values.Results VAP was confirmed in 76 patients (57.58％).In VAP patients (VAP group) and non-VAP patients (non-VAP group),the level of sTREM-1 in BALF was 32.35 (30.08-41.72) and 18.92(11.89-31.72) ng/L,and the level of sTREM-1 in EBC was 1.57 (1.02-2.61) and 0.41(0.19-1.61)ng/L respectively.The level of sTREM-1 in BALF and in EBC in VAP group was significantly higher than that in non-VAP group (P ＜0.05).The optimum cutoff value for sTREM-1 in BALF according to the maximum Youden index was 23.61 ng/L.This cutoff value had 85.5％ sensitivity and 73.1％ specificity,with 0.813 area under the curve.sTREM-1 in BALF had excellent correlation with that in EBC (R2 =0.78,P ＜ 0.05).Conclusions The results of this prospective study suggest that sTREM-1 levels in BALF and EBC have better roles in facilitating the diagnosis of VAP and thus may be practically recommended to guide the administration of antibiotics when VAP is suspected.
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Objective To investigate the effect of ulinastatin treatment on the inflammatory factor expression and prognosis in patients with ventilator-associated pneumonia (VAP). Methods One hundred patients with VAP were enrolled, and the patients were given the standardized treatment of VAP. The patents were divided into high dose group (33 cases, using the ulinastatin 20 000 U/d), normal dose group (34 cases, using the ulinastatin 10 000 U/d) and control group (33 cases, no using the ulinastatin) by random digits table method. The serum C-reactive protein (CRP), procalcitonin, interleukin (IL)-6 and tumor necrosis factor (TNF)-αlevels at the first, third, fifth and seventh day of diagnosis were detected. All the patients were followed up for 1 month, and the antibiotics treatment time, mechanical ventilation time, ICU stay time and mortality were recorded. Results The CRP, procalcitonin, TNF-αand IL-6 from the first day of diagnosis to the seventh day of diagnosis in 3 groups showed the downward trend, and there were statistical differences (P0.05). At the third, fifth and seventh day of diagnosis, the TNF-α levels in high dose group were (46.02 ± 4.65), (23.88 ± 7.76) and (11.05 ± 2.56) ng/L, the IL-6 levels were (15.53 ± 4.54), (11.33 ± 3.45) and (6.62 ± 2.45) ng/L;the TNF-αlevels in normal dose group were (56.02 ± 6.42), (38.88 ± 9.34) and (27.05 ± 3.42) ng/L, the IL-6 levels were (18.23 ± 2.45), (15.33 ± 4.34) and (11.23 ± 3.34) ng/L; the TNF-α levels in control group were (68.13 ± 4.77), (52.88 ± 7.46) and (42.12 ± 3.76) ng/L, the IL-6 levels were (20.02 ± 3.23), (17.23 ± 2.34) and (15.33 ± 2.33) ng/L. The TNF-αand IL-6 levels at the third, fifth and seventh day of diagnosis in high dose group were significantly lower than those in normal dose group and control group, and those in the normal dose group were significantly lower than those in control group, and there were statistical differences (P0.05). Conclusions Ulinastatin can inhibit the expression of IL-6 and TNF-α in patents with VAP, shorten the antibiotics treatment time, mechanical ventilation time, ICU stay time and mortality, and improve prognosis.
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ObjectiveTo investigate the risk factors and pathogenic characteristics of catheterrelated infection (CRI) in intensive care unit (ICU),so as to find a better way for its treatment.Methods Retrospective analysis was performed on 247 deep-venous catheter (DVC) from January 2007 to December 2010.ResultsAmong 247 patients,positive results of 41 patients diagnosed CRI,negative results of 206 patients undiagnosed CRI.Compared with undiagnosed CRI patients,found the correlation of the underlying infectious diseases,indwelling time of catheter and puncture sites associated with CRI occurred(P ＜ 0.05 ).CRI major pathogen was gram-positive bacteria (58.5％,24/41 ),in which Staphylococcus epidermis was the major pathogenic bacteria(22.0％,9/41).The drug resistance occurred in most pathogen.Conclusions The occurrence of CRI is related with multiple clinical factors.The gram-positive bacteria is the major pathogen.The etiological monitor should be enforced in patients with DVC.
