Astrocyte elevated gene 1: biological functions and molecular mechanism in cancer and beyond

Since its discovery, nearly one decade of research on astrocyte elevated gene 1 (AEG-1) has witnessed expanding knowledge of this molecule, ranging from its role in cancer biology to molecular mechanisms underlying the biological functions. As a multifunctional oncoprotein, AEG-1 has been shown to overexpress in multiple types of human cancer, and the elevation of AEG-1 in tumor cells leads to enhanced phenotypes characteristic of malignant aggressiveness, including increased abilities to proliferate robustly, to invade surrounding tissues, to migrate, to induce neovascularization, and to enhance chemoresistance. The multifunctional role of AEG-1 in tumor development and progression has been found to be associated with several signaling cascades, namely, 1) activation of NF-kappa B, partially through direct interaction with p65; 2) PI3K/AKT signaling triggered by AEG-1 indirectly; 3) enhancement of the transcriptional activity of beta-catenin by indirect activation of MAPK and induction of LEF1; 4) regulation of mi/siRNA-mediated gene silencing by interacting with SND1; and 5) promotion of protective autophagy; in addition to possibly unknown mechanisms. Elevated AEG-1 expression is seen in nearly all tumor types, and in most cases AEG-1 positively correlates with tumor progression and poorer patient survival. Taken together, AEG-1 might represent a potential prognostic biomarker and therapeutic target

A New Method for Analyzing Integrated Stealth Ability of Penetration Aircraft

AbstractTaking into account the limitations of existing stealth performance analysis methods, a method termed as the integrated stealth performance analysis method is proposed for evaluating the stealth ability of the penetration aircraft. Based on various target radar cross section (RCS) scattering characters, this article integrates the relevant parameters needed for building up target circumferential RCS scattering model and proposes the RCS scattering controlling parameters to control the changing trends of the relevant model RCS scattering characters. According to the radar dynamic detecting characters during the whole penetration course, a dynamic stealth performance evaluating model is proposed accompanied by a series of stealth ability estimation rules. This new analysis method can enhance the integrality and dependability of the stealth analysis conclusions and summarize the relationship between the target RCS scattering characters and their effects on stealth performance. The rules indicated by this relationship can be used as the reference for designing new type of stealth aircraft and setting up specific penetration tactics

Activation of Extracellular-signal Regulated Kinase (ERK1/2) by Fluid Shear is Ca\u3csup\u3e2+\u3c/sup\u3e- and ATP-dependent in MC3T3-E1 Osteoblasts

To determine the role of Ca2+ signaling in activation of the Mitogen-Activated Protein Kinase (MAPK) pathway, we subjected MC3T3-E1 pre-osteoblastic cells to inhibitors of Ca2+ signaling during application of fluid shear stress (FSS). FSS only activated ERK1/2, rapidly inducing phosphorylation within 5 min of the onset of shear. Phosphorylation of ERK1/2 (pERK1/2) was significantly reduced when Cai2+ was chelated with BAPTA or when Ca2+ was removed from the flow media. Inhibition of both the L-type voltage-sensitive Ca2+ channel and the mechanosensitive cation-selective channel blocked FSS-induced pERK1/2. Inhibition of phospholipase C with U73122 significantly reduced pERK1/2. This inhibition did not result from blockage of intracellular Ca2+ release, but a loss of PKC activation. Recent data suggests a role of ATP release and purinergic receptor activation in mechanotransduction. Apyrase-mediated hydrolysis of extracellular ATP completely blocked FSS-induced phosphorylation of ERK1/2, while the addition of exogenous ATP to static cells mimicked the effects of FSS on pERK1/2. Two P2 receptors, P2Y2 and P2X7, have been associated with the anabolic responses of bone to mechanical loading. Using both iRNA techniques and primary osteoblasts isolated from P2X7 knockout mice, we found that the P2X7, but not the P2Y2, purinergic receptor was involved in ERK1/2 activation under FSS. These data suggest that FSS-induced ERK1/2 phosphorylation requires Ca2+-dependent ATP release, however both increased Cai2+ and PKC activation are needed for complete activation. Further, this ATP-dependent ERK1/2 phosphorylation is mediated through P2X7, but not P2Y2, purinergic receptors

Obciążenie chorobami układu sercowo-naczyniowego u osób hospitalizowanych w szpitalu w Guangzhou w Chinach, w latach 2006–2015

Introduction. To explore the epidemiological characters of cardiovascular disease (CVD) in patients and to give a certain clues for disease prevention and clinical treatment. Material and methods. We carried out an investigation using retrospective study method by the medical records retrieval system, and extracted the data of inpatients suffered from CVD in a hospital in Guangzhou from 2006 to 2015, including age, gender, disease onset time, clinical diagnosis, hospitalization days, cost and so on. Results. The average admissions per 5 years kept increasing in the study period. Most inpatients suffered from the CVD in December (n = 9288, 9.10%), while least in February (n = 7309, 7.16%). Most of the inpatients were 66–75-years- -old (n = 24,891, 24.37%). Gender ratio (male vs. female) of CVD inpatients showed a downward trend came with age. The gender ratio was 1.9 and 0.99 among inpatients below 26-years-old and above 85-years-old, respectively. Most common CVD were ischemic heart diseases (29.46%), cerebrovascular diseases (21.59%) and hypertensive diseases (15.18%). The adjusted hospitalization cost was 4600.30 USD in 2006 and 5473.66 USD in 2006, while the average hospitalization days were 15.63 in 2006 and 9.98 in 2015. Conclusions. More attention should be paid to the middle and elderly people with CVD risk factors, especially the senile women, to reduce the disease burden. The change of gender ratio suggested there may be other significant causes leading to the gender differences besides estrogen.Wstęp. Badanie przeprowadzono w celu oceny cech epidemiologicznych chorych hospitalizowanych z powodu chorób układu sercowo-naczyniowego i sformułowanie wskazówek dotyczących zapobiegania tym chorobom oraz ich leczenia. Materiał i metody. Badanie przeprowadzono w sposób retrospektywny na podstawie analizy danych medycznych, korzystając z dokumentacji pacjentów hospitalizowanych z powodu chorób układu sercowo-naczyniowego w szpitalu w Guangzhou w latach 2006–2015. Dane włączone do analizy obejmowały między innymi wiek, płeć, czas rozpoczęcia choroby, rozpoznanie kliniczne, okres hospitalizacji (dni), koszty związane z hospitalizacją. Wyniki. Średnia liczba hospitalizacji na 5 lat zwiększała się stale w badanym okresie. Najwięcej chorych zgłaszało się do szpitala z powodu chorób układu sercowo-naczyniowego w grudniu (n = 9288; 9,10%), natomiast najmniej w lutym (n = 7309; 7,16%). Największą grupę hospitalizowanych stanowiły osoby w wieku 66–75 lat (n = 24 891; 24,37%). Wartość współczynnika płci chorych (stosunek liczby mężczyzn do liczby kobiet) wśród osób hospitalizowanych z powodu chorób układu sercowo-naczyniowego zmniejszała się z wiekiem. Współczynnik ten wynosił 1,9 i 0,99, odpowiednio, w grupach chorych w wieku poniżej 26 lat oraz powyżej 85 lat. Do najczęstszych CVD należały choroba niedokrwienna serca (29,46%), choroba naczyniowa mózgu (21,59%) i nadciśnienie tętnicze (15,18%). Skorygowane koszty hospitalizacji wynosiły 4600,30 USD w 2006 roku i 5473,66 USD w 2015 roku, natomiast średni czas hospitalizacji wynosił odpowiednio 15,63 i 9,98 dnia. Wnioski. Aby zmniejszyć obciążenie chorobami sercowo-naczyniowymi należy zwrócić większa uwagę na osoby w średnim i podeszłym wieku, u których występują czynniki ryzyka sercowo-naczyniowego; dotyczy to zwłaszcza starszych kobiet. Zmiana proporcji płci chorych sugeruje, że oprócz estrogenu mogą istnieć inne przyczyny powodujące różnicę w liczbie zachorowań na choroby sercowo-naczyniowe

Germline-Competent Mouse-Induced Pluripotent Stem Cell Lines Generated on Human Fibroblasts without Exogenous Leukemia Inhibitory Factor

Induced pluripotent stem (iPS) cells have attracted enormous attention due to their vast potential in regenerative medicine, pharmaceutical screening and basic research. Most prior established iPS cell lines were derived and maintained on mouse embryonic fibroblast (MEF) cells supplemented with exogenous leukemia inhibitory factor (LIF). Drawbacks of MEF cells impede optimization as well as dissection of reprogramming events and limit the usage of iPS cell derivatives in therapeutic applications. In this study, we develop a reproducible protocol for efficient reprogramming mouse neural progenitor cells (NPCs) on human foreskin fibroblast (HFF) cells via retroviral transfer of human transcriptional factors OCT4/SOX2/KLF4/C-MYC. Two independent iPS cell lines are derived without exogenous LIF. They display typical undifferentiated morphology and express pluripotency markers Oct4 and Sox2. Transgenes are inactivated and the endogenous Oct4 promoter is completely demethylated in the established iPS cell lines, indicating a fully reprogrammed state. Moreover, the iPS cells can spontaneously differentiate or be induced into various cell types of three embryonic germ layers in vitro and in vivo when they are injected into immunodeficient mice for teratoma formation. Importantly, iPS cells extensively integrate with various host tissues and contribute to the germline when injected into the blastocysts. Interestingly, these two iPS cell lines, while both pluripotent, exhibit distinctive differentiation tendencies towards different lineages. Taken together, the data describe the first genuine mouse iPS cell lines generated on human feeder cells without exogenous LIF, providing a reliable tool for understanding the molecular mechanisms of nuclear reprogramming

Clinical application of amplification-based versus amplification-free metagenomic next-generation sequencing test in infectious diseases

BackgroundRecently, metagenomic next-generation sequencing (mNGS) has been used in the diagnosis of infectious diseases (IDs) as an emerging and powerful tool. However, whether the complicated methodological variation in mNGS detections makes a difference in their clinical performance is still unknown. Here we conducted a method study on the clinical application of mNGS tests in the DNA detection of IDs.MethodsWe analyzed the effect of several potential factors in the whole process of mNGS for DNA detection on microorganism identification in 98 samples of suspected ID patients by amplification-based mNGS. The amplification-based and amplification-free mNGS tests were successfully performed in 41 samples. Then we compared the clinical application of the two mNGS methods in the DNA detection of IDs.ResultsWe found that a higher concentration of extracted nucleic acid was more conducive to detecting microorganisms. Other potential factors, such as read depth and proportion of human reads, might not be attributed to microorganism identification. The concordance rate of amplification-based and amplification-free mNGS results was 80.5% (33/41) in the patients with suspected IDs. Amplification-based mNGS showed approximately 16.7% higher sensitivity than amplification-free mNGS. However, 4 cases with causative pathogens only detected by amplification-based mNGS were finally proved false-positive. In addition, empirical antibiotic treatments were adjusted in 18 patients following mNGS testing with unexpected pathogens.ConclusionsAmplification-based and amplification-free mNGS tests showed their specific advantages and disadvantages in the diagnosis of IDs. The clinical application of mNGS still needs more exploration from a methodological perspective. With advanced technology and standardized procedure, mNGS will play a promising role in the diagnosis of IDs and help guide the use of antibiotics

Thymopentin (TP5), an immunomodulatory peptide, suppresses proliferation and induces differentiation in HL-60 cells

AbstractThymopentin (Arg–Lys–Asp–Val–Tyr, TP5) has shown immuno-regulatory activities in humans. In the present study, we investigated the effects of TP5 on the proliferation and differentiation of a human promyelocyte leukemia cell line, HL-60. It is noteworthy that TP5 displayed concentration-dependent inhibitory effects on the proliferation and colony formation of HL-60 cells. Furthermore, the decrease or even disappearance of AgNORs from nucleoli was observed in HL-60 cells after the treatment with TP5. The suppression induced by TP5 was accompanied by an accumulation of cell cycle in the G0/G1 phase. Moreover, TP5 significantly increased the NBT-reduction activity of HL-60 cells. Cytofluorometric and morphologic analysis indicated that TP5 had induced differentiation along the granulocytes lineage in HL-60 cells. d-tubocurarine (TUB) significantly antagonized the inhibitory effects induced by TP5, whereas atropine did not exhibit such effect. All the results indicated that TP5 was able to significantly inhibit proliferation and induce differentiation in HL-60 cells. Our observations also implied that TP5 not only acted as an immunomodulatory factor in cancer chemotherapy, but is also a potential chemotherapeutic agent in the human leukemia therapy

Decrease in CD4+CD25+FoxP3+ Treg cells after pulmonary resection in the treatment of cavity multidrug-resistant tuberculosis

SummaryObjectivesImmune regulatory mechanisms may limit the immunopathologic condition of infection with Mycobacterium tuberculosis and suppress cellular immune responses in the host. We investigated the CD4+CD25+FoxP3+ circulating regulatory T cells (Treg) in patients with cavity multidrug-resistant tuberculosis (MDR-TB) before and after surgery.MethodsWe compared the proportion of Treg cells in 13 patients with cavity MDR-TB pre- and postoperatively and in 10 healthy control subjects by flow cytometry using three specific markers in peripheral blood lymphocytes: cell-surface CD4 and CD25 expression and intracellular FoxP3 expression.ResultsThe proportion of CD4+CD25high and CD4+CD25+FoxP3+ Treg was significantly higher in patients with cavity MDR-TB and at 1-month postoperatively than in healthy controls (p<0.001). The proportion of CD4+ and CD4+CD25− cells was significantly lower in patients with cavity MDR-TB than in controls (p<0.001). Pre- and postoperative proportions of CD4+CD25high and CD4+CD25+FoxP3+ Treg cells showed a positive correlation (r=0.878, p<0.001).ConclusionCirculating Treg cells are increased in proportion in patients with cavity MDR-TB and decreased after surgery. Infection with M. tuberculosis may induce Treg cell-surface molecular changes with increased numbers of cells