Role of hepatitis B surface antigen in the development of hepatocellular carcinoma: regulation of lymphoid enhancer-binding factor 1

<p>Abstract</p> <p>Background</p> <p>There are around 350 million of hepatitis B surface antigen (HBsAg) carriers worldwide, and among them, high risk of developing hepatocellular carcinoma (HCC) has been identified by epidemiological studies. To date, the molecular role of HBsAg in HCC development has not been fully studied. We have previously reported that in cell cultures, HBsAg up-regulated the expression of lymphoid enhancer-binding factor 1 (LEF-1), a key component of the <it>Wnt </it>pathway. In this study we aimed to study this effect of HBsAg on LEF-1 in the development of HCC.</p> <p>Methods</p> <p>Expression of HBsAg, LEF-1 and its downstream effector genes were compared among 30 HCCs, their peritumor tissue counterparts and 9 normal control liver tissues by quantitative real-time PCR. In addition, immunohistochemical staining studies on HBsAg and LEF-1 expression were conducted among these samples.</p> <p>Results</p> <p>The expression of LEF-1 was compared between 13 HBsAg positive HCC tissues and 17 HBsAg negative HCC tissues. Simultaneous detection of LEF-1 and HBsAg was observed in HBsAg positive HCC tissues and, additionally, the simultaneous detection of HBsAg and LEF-1 was more pronounced in peritumor tissues, compared to that in the tumor tissues. The distribution of cellular LEF-1 in peritumor tissues was predominantly in the cytoplasm; while LEF-1 in the tumor tissues was located either exclusively in the nucleus or both in the nucleus and cytoplasm. By real-time PCR, the expression levels of LEF-1 downstream effector genes <it>cyclin D1 </it>and <it>c-myc </it>were higher in peritumor cells compared to that of the tumor cells. However, a 38 kDa truncated isoform of LEF-1, rather than the 55 kDa wild-type LEF-1, was significantly elevated in the HBsAg positive tumor cells.</p> <p>Conclusion</p> <p>Data indicate that deregulation of the <it>Wnt </it>pathway by HBsAg occurred in HBV-associated HCCs, but was more pronounced in the peritumor cells. It is speculated that HBsAg could stimulate proliferation and functional modification of hepatocytes via LEF-1 through the <it>Wnt </it>pathway at the pre-malignant stage.</p

Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers

Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

Analysis on epidemiological and drug resistance characteristics of lymph node tuberculosis from Hunan province, China

ObjectivesTo investigate the clinical epidemiological and drug resistance (DR) characteristics of lymph node tuberculosis (LNTB) in Hunan Province which locates in South-central China, and to provide scientific clues for effective prevention and treatment of LNTB.MethodsWe retrospectively collected LNTB patients with Mycobacterium tuberculosis culture positive at Hunan Chest Hospital, the biggest TB reference hospital in South-central China, from January 2013 to December 2021. The multiple demographic, clinical and drug susceptibility data of patients were collected from the hospital’s electronic patient records. Descriptive statistical methods, Chi-square test and logistic regression analysis were employed as statistical methods.ResultsOf the 577 LNTB cases, 373 (64.64%) were males, 352 (61.01%) were farmers; majority (161, 33.10%) aged at 20–29 years old; 147 (25.48%) had simple LNTB, 350 (60.66%) had LNTB combined with pulmonary TB (PTB) (defined as LNTB-PTB), and 80 (13.86%) had LNTB combined with other extrapulmonary TB (EPTB) (defined as LNTB-EPTB). A total of 345 (59.79%, 345/577) LNTB patients had cervical node infection, and the simple LNTB patients (81.63%, 120/147) had higher proportion of this infection than LNTB-PTB (51.71%, 181/350) and LNTB-EPTB (55.00%, 44/80) (both p values &lt;0.017), respectively. LNTB-EPTB was more inclined to have abdominal tuberculous LNs (20%, 16/80) and at least four tuberculous lesions (22.50%, 18/80) than simple LNTB and LNTB-PTB. Seventy-seven (13.34%) and 119 (20.62%) were resistant to rifampicin (RIF) and isoniazid (INH), respectively; 72 (12.48%) were multi-drug resistant (MDR), and a total of 150 (26.00%) were DR (resistant to at least one of RIF, INH, ethambutol and streptomycin). LNTB patients aged 30–34 and 50–54 years old (compared to those aged &lt;30 years) were independent predictors of RIF resistance (RR) (ORs were 3.47 and 2.83, respectively; 95% CIs were 1.64–7.35 and 1.08–7.46, respectively).ConclusionOur study disclosed the epidemiological and DR characteristics of LNTB in Hunan Province, China. High LNTB prevalence was found in younger people while high RR LNTB prevalence was found in older ones, suggesting that we should conduct further studies to clarify the occurrence of RR in LNTB, meanwhile, strengthen the diagnoses and treatments of LNTB to prevent the emergence of RR

Measurement of B(t->Wb)/B(t->Wq) at the Collider Detector at Fermilab

We present a measurement of the ratio of top-quark branching fractions R= B(t -> Wb)/B(t -> Wq), where q can be a b, s or a d quark, using lepton-plus-jets and dilepton data sets with integrated luminosity of ~162 pb^{-1} collected with the Collider Detector at Fermilab during Run II of the Tevatron. The measurement is derived from the relative numbers of t-tbar events with different multiplicity of identified secondary vertices. We set a lower limit of R > 0.61 at 95% confidence level.Comment: 7 pages, 2 figures, published in Physical Review Letters; changes made to be consistent with published versio

Measurement of the Lifetime Difference Between B_s Mass Eigenstates

We present measurements of the lifetimes and polarization amplitudes for B_s --> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and light (L) mass eigenstates in the B_s system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07 +{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s and average Gamma_s, of the decay rates of the two eigenstates, the results are DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47 +{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters on 16 March 2005; revisions are for length and typesetting only, no changes in results or conclusion

Measurement of WγW\gamma and ZγZ\gamma Production in ppˉp\bar{p} Collisions at s\sqrt{s} = 1.96 TeV

The Standard Model predictions for $W\gamma$ and $Z\gamma$ production are tested using an integrated luminosity of 200 pb$^{-1}$ of \ppbar collision data collected at the Collider Detector at Fermilab. The cross sections are measured selecting leptonic decays of the $W$ and $Z$ bosons, and photons with transverse energy $E_T>7$ GeV that are well separated from leptons. The production cross sections and kinematic distributions for the $W\gamma$ and $Z\gamma$ are compared to SM predictions.Comment: 7 pages, 4 figures, submitted to PR

Measurement of the Ratio of Branching Fractions B(D0 -> K+ pi-)/B(D0 -> K- pi+) using the CDF II Detector

We present a measurement of R_B, the ratio of the branching fraction for the rare decay D0 -> K+ pi- to that for the Cabibbo-favored decay D0 -> K- pi+. Charge conjugate decays are implicitly included. A signal of 2005 +/- 104 events for the decay D0 -> K+ pi- is obtained using the CDF II detector at the Fermilab Tevatron collider. The data set corresponds to an integrated luminosity of 0.35 1/fb produced in p-bar/p collisions at sqrt{s}=1.96 TeV. Assuming no mixing, we find R_B = [ 4.05 +/- 0.21 (stat) +/- 0.11 (syst) ] x 10(-3). This measurement is consistent with the world average, and comparable in accuracy with the best measurements from other experiments.Comment: 7 pages, 3 figure

Measurement of the Strong Coupling Constant from Inclusive Jet Production at the Tevatron pˉp\bar pp Collider

We report a measurement of the strong coupling constant, $\alpha_s(M_Z)$, extracted from inclusive jet production in $p\bar{p}$ collisions at $\sqrt{s}=$1800 GeV. The QCD prediction for the evolution of $\alpha_s$ with jet transverse energy $E_T$ is tested over the range 40<$E_T$<450 GeV using $E_T$ for the renormalization scale. The data show good agreement with QCD in the region below 250 GeV. In the text we discuss the data-theory comparison in the region from 250 to 450 GeV. The value of $\alpha_s$ at the mass of the $Z^0$ boson averaged over the range 40<$E_T$<250 GeV is found to be $\alpha_s(M_{Z})= 0.1178 \pm 0.0001{(\rm stat)}^{+0.0081}_{-0.0095}{\rm (exp. syst)}$. The associated theoretical uncertainties are mainly due to the choice of renormalization scale (^{+6%}_{-4%}) and input parton distribution functions (5%).Comment: 7 pages, 3 figures, using RevTeX. Submitted to Physical Review Letter