Abstract Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, ...the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.
Aim To investigate the potential of iodine concentration (IC) determined using virtual monochromatic spectral computed tomography (CT) to predict the response of gastric carcinomas to preoperative ...neoadjuvant chemotherapy (NC). Materials and methods A total of 20 patients were enrolled who underwent two spectral CT examinations (1 week before and two cycles after NC). The percentage change in tumour thickness (%ΔCWT) and in IC on the arterial phase (%ΔIC-a) and venous phase (%ΔIC-v) after NC were calculated and compared for different histopathological regression grades and response groups. The diagnostic efficacies to discriminate good response (GR) and poor response (PR) of the above three parameters were evaluated using receiver operating characteristic (ROC) curves. Results The decrease rate of %ΔIC-a for the GR group was higher than that for the PR group (−0.59 −0.76, −0.20 versus −0.11 −0.75, 0.92, p =0.012). There was no significant difference in the %ΔIC-v and %ΔCWT values between the GR and PR groups ( p =0.076 and p =0.779, respectively). The areas under the ROC curve (AUC) values were 0.857, 0.762, and 0.542 for %ΔIC-a, %ΔIC-v, and %ΔCWT, respectively, in the response prediction. The cut-off value for identifying PR was a decrease rate of <52.9% for %ΔIC-a, and the sensitivity and specificity values were 0.857 and 0.833. Conclusion Changes in the IC for gastric carcinomas following NC were detected using spectral CT and correlated with histopathological regression. The prediction efficacy for IC was better than that for tumour thickness, with IC on the arterial phase being a better predictor than IC on the venous phase.
MicroRNA-146a and Human Disease Li, L; Chen, X.-P; Li, Y.-J
Scandinavian journal of immunology,
April 2010, Letnik:
71, Številka:
4
Journal Article
Recenzirano
MicroRNAs (MiRNAs) belong to a class of small non-coding regulatory RNAs that act through repression of protein expression at post-transcriptional level and emerge to play important roles in many ...physiological and pathophysiological processes. MiR-146a is a miRNA supposed to regulate innate immune, inflammatory response and antiviral pathway negatively. In this review, we focus on the recent progress in functional role of miR-146a in innate immune, inflammatory response, virus infection and human diseases. Together, these findings indicate that manipulation of miR-146a expression may represent a potential new therapy for several human diseases. Potential use of miR-146a as a biomarker for disease diagnosis, prevention and treatment is also discussed.
State-of-charge (SOC) estimation is one of the most challengeable tasks for battery management system (BMS) in electric vehicles. Since the external factors (voltage, current, temperature, ...arrangement of the batteries, etc.) are complicated, the formula of SOC is difficult to deduce and the existent SOC estimation methods are not generally suitable for the same vehicle running in different road conditions. In this paper, we propose a new SOC estimation based on an optimized support vector machine for regression (SVR) with double search optimization process. Our developed method is tested by simulation experiments in the ADVISOR, with a comparison of the estimations based on artificial neural network (ANN). It is demonstrated that our method is simpler and more accurate than that based on ANN to deal with the SOC estimation task.
Pyogenic liver abscess (PLA) is a potentially life-threatening disease in many parts of the world, especially in Asia. The aim of this study was to quantify the proportion of common pathogens in ...patients with PLA in China, using a meta-analysis method based on systematic review of published studies. Several electronic databases were searched to identify the studies reporting the pathogens of PLA. We performed a meta-analysis to calculate the pooled proportion of pathogens and subgroup analysis among the included studies using R 3.1.1 software. In total, 183 studies were included in our final analysis,
Klebsiella
spp (54 %),
Escherichia
spp (29 %),
Enterobacter
spp (9 %),
Proteus
spp (6 %) and
Pseudomonas
spp (5 %) comprised the major gram-negative bacteria. Gram-positive bacteria mainly included
Staphylococcus
spp (13 %),
Streptococcus
spp (8 %) and
Enterococcus
spp (7 %). The distribution of pathogens in PLA patients were different in different economic regions in China. The proportion of
Klebsiella
spp had an upward tendency in recent years compared to other pathogens. In addition, the proportion of common pathogens in PLA patients with diabetes mellitus (DM) were carried out indicating that the dominant pathogens were
Klebsiella
spp (66 %),
Escherichia
spp (21 %) and
Enterobacter
spp (11 %). This meta-analysis showed that the main pathogens of PLA were
Klebsiella
spp,
Escherichia
spp,
Staphylococcus
spp, and
Enterobacter
spp in China. To ensure a precise estimate of the epidemiology of the pathogens, further large-scale or even a population-based study is needed.
Metastasis is the chief cause of mortality from cancer, but the mechanisms leading to metastasis are poorly understood. We used a proteomics approach to screen for metastasis-associated proteins and ...found that collapsin response mediator protein-4 (CRMP4) expression was inversely associated with the lymph node metastasis of prostate cancer (PCa). Subsequent in vitro and in vivo studies revealed that overexpression of CRMP4 not only suppressed the invasion ability of PCa cells, but also strongly inhibited tumor metastasis in an animal model. Furthermore, methylation of a CpG island within the promoter region of the CRMP4 gene is responsible for downregulation of CRMP4 expression. Thus, in this study, we show new function of CRMP4 as a metastasis-suppressor in PCa. The findings provide new mechanistic insights into metastasis and therapeutic potential for this most common male cancer.
Protection against humoral injury mediated by donor‐specific antibodies (DSA), also known as accommodation, may allow for long‐term allograft survival in presensitized recipients. In the present ...study, we determined the role of complement in renal allograft accommodation in donor skin‐presensitized nonhuman primates under conventional immunosuppression. Donor skin allografts were transplanted to presensitized recipients 14 days prior to renal transplantation. Renal allografts not receiving any immunosuppressive treatment developed accelerated rejection with predominantly humoral injury, which was not prevented using conventional cyclosporine (CsA) triple therapy. Inhibition of complement activation with the Yunnan‐cobra venom factor (Y‐CVF) successfully prevented accelerated antibody‐mediated rejection and resulted in successful accommodation and long‐term renal allograft survival in most presensitized recipients. Accommodation in this model was associated with the prevention of the early antibody responses induced against donor antigens by complement inhibition. Some antiapoptotic proteins and complement regulatory proteins, including Bcl‐2, CD59, CD46 and clusterin, were upregulated in the surviving renal allografts. These results suggest that the complement inhibition‐based strategy may be valuable alternative in future clinical cross‐match positive or ABO‐incompatible transplantation.
Short‐term inhibition of complement prevents the early antibody response induced against donor antigens and enables renal allograft accommodation and long‐term engraftment in donor skin‐presensitized cynomolgus monkeys. See editorial by Platt on page 2007.
Circular electron positron colliders, such as the CEPC and FCC-ee, have been proposed to measure Higgs boson properties precisely, test the Standard Model, search for physics beyond the Standard ...Model, and so on. One of the important goals of these colliders is to measure the
W
boson mass with great precision by taking data around the
W
-pair production threshold. In this paper, the data-taking scheme is investigated to maximize the achievable precisions of the
W
boson mass and width with a threshold scan, when various systematic uncertainties are taken into account. The study shows that an optimal and realistic data-taking scheme is to collect data at three center-of-mass energies and that precisions of 1.0 MeV and 3.4 MeV can be achieved for the mass and width of the
W
boson, respectively, with a total integrated luminosity of
L
=
3.2
ab
-
1
and several assumptions of the systematic uncertainty sources.
Ecdysone 20‐monooxygenase (E20MO), a cytochrome P450 monooxygenase (CYP314A1), catalyses the conversion of ecdysone (E) to 20‐hydroxyecdysone (20E). We report here the cloning and characterization of ...the Halloween gene Shade (Shd) encoding E20MO in the Colorado potato beetle, Leptinotarsa decemlineata. LdSHD has five conserved motifs typical of insect P450s, ie the Helix‐C, Helix‐I, Helix‐K, PxxFxPE/DRF (PERF) and heme‐binding motifs. LdShd was expressed in developing eggs, the first to fourth instars, wandering larvae, pupae and adults, with statistically significant fluctuations. Its mRNA was ubiquitously distributed in the head, thorax and abdomen. The recombinant LdSHD protein expressed in Spodoptera frugiperda 9 (Sf9) cells catalysed the conversion of E to 20E. Dietary introduction of double‐stranded RNA (dsRNA) of LdShd into the second instar larvae successfully knocked down the LdShd expression level, decreased the mRNA level of the ecdysone receptor (LdEcR) gene, caused larval lethality, delayed development and affected pupation. Moreover, ingestion of LdShd‐dsRNA by the fourth instars also down‐regulated LdShd and LdEcR expression, reduced the 20E titre, and negatively influenced pupation. Introduction of 20E and a nonsteroidal ecdysteroid agonist halofenozide into the LdShd‐dsRNA‐ingested second instars, and of halofenozide into the LdShd‐dsRNA‐ingested fourth instars almost completely relieved the negative effects on larval performance. Thus, LdSHD functions to regulate metamorphotic processes by converting E to 20E in a coleopteran insect species Le. decemlineata.
Summary
Deficiency of CARD9 (caspase recruitment domain‐containing protein 9) has been reported in individuals with recurrent and invasive fungal infections. We report on a patient who first had ...Trichosporon asahii affecting the skin then Candida albicans infections involving the digestive tract and knee joint, along with elevated serum IgE. After stimulation with C. albicans, peripheral blood mononuclear cells of this patient produced less tumour necrosis factor‐α, interferon‐γ and interleukin‐17 than those of healthy controls. Furthermore, the serum IgE levels of this patient were positively correlated with the severity of fungal infection during the course of treatment. Sanger sequencing identified one homozygous frameshift mutation (p.D274fsX60) in CARD9. We further performed a review including 48 cases with CARD9 deficiency. According to the data published previously, CARD9‐deficient patients demonstrated obviously elevated IgE in serum (median 1300 IU mL−1), which could distinguish them from otherwise healthy people with fungal infections (area under the curve 0·94, P < 0·001). Patients carrying the mutations Q289X and Q295X had a higher mortality rate (24% vs. 0%, P < 0·05). Patients with the mutations R18W, R35Q, R70W, G72S or Y91H in the CARD domain, and the nonsense mutation Q295X in the coiled‐coil domain, seemed to be more prone to Candida infections (90% vs. 20%, P < 0·005) and central nervous system infections (60% vs. 12%, P < 0·005).
What's already known about this topic?
CARD9 deficiency is a rare autosomal recessive genetic defect in T helper 17 immunity, resulting in susceptibility to recurrent and invasive fungal infections.
Patients with genetic defects in T helper 17 immunity are prone to hyper‐IgE syndrome.
What does this study add?
We report a patient with CARD9 p.D274fsX60 mutation manifested as multiple organs infections by Trichosporon asahii and Candida albicans.
This study enriches the phenotypic spectrum of CARD9 deficiency.
IgE level seems to be a possible clue for diagnosis or therapeutic effect of fungal infection in CARD9‐deficient patients.
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