A Retrospective Study on Pathologic Features and Racial Disparities in Prostate Cancer

We reviewed more than 3,000 pathology reports on prostate cancer-related surgical specimens and analyzed racial disparities in histological and clinical features at the time of initial biopsy, diagnosis of prostate cancer, and prostatectomy, as well as in characteristics of tumor evolution between African American and Caucasian patients. As compared to Caucasians, African American patients had younger age, higher cancer detection rate, higher Gleason score of prostate cancer, and more bilateral involvement of the prostate. African Americans also had larger prostates, greater volume of tumor, and more positive margins. The diagnosis of HGPIN or ASAP in prostate biopsies and African American race conferred an increased risk of diagnosis of prostate cancer. The interval between prior noncancerous biopsy and the subsequent biopsy with diagnosis of prostate cancer was shorter in men with HGPIN, with ASAP, or of African American race

Molecular identification of original plants of Fritillariae cirrhosae bulbus, a Tradtional Chinese Cedicine (TCM) using plant DNA barcoding

Background: DNA barcoding is a widely used tool that enables rapid and accurate identification of species based on standardized DNA regions.Materials and Methods: In this study, potential DNA barcodes, namely three plastid regions (rbcL, trnH-psbA and matK) and one nuclear ribosomal internal transcribed spacer (ITS) were adopted for species identification of original plants of Fritillariae Cirrhosae Bulbus.Results: The rbcL and trnH-psbA regions showed better success rate of PCR amplification and DNA sequencing, as well as superior discriminatory ability. On the contrary, ITS region did not possess effective genetic variation and matK was faced with low success rate of sequencing. Combination of multi-loci sequences could improve identification ability of DNA barcoding. The trnH-psbA + rbcL could discriminate 25% - 100% species based on the Blast, Tree-Building and Distance methods.Conclusion: The potential DNA barcodes could not completely solving species identification of botanic origins of Fritillariae Cirrhosae Bulbus. In future, we should pay more attention to super-barcoding or specific barcode that enhance ability to discriminate the closely related plants.Keywords: Fritillariae Cirrhosae Bulbus, species identification, DNA barcoding, internal transcribed spacer (ITS), traditional Chinese medicine (TCM

Roles of circulating soluble interleukin (IL)-6 receptor and IL-6 receptor expression on CD4+ T cells in patients with chronic hepatitis B

SummaryObjectivesThe objective of this study was to investigate the potential clinical roles of circulating soluble interleukin (IL)-6 receptor (sIL-6R) and IL-6R expression on CD4+ T cells (CD4+ IL-6R+ T cells) in chronic hepatitis B (CHB) patients.MethodsOne hundred and thirty-three subjects, including 72 CHB patients, 27 asymptomatic carriers, eight acute hepatitis B (AHB) patients, and 26 healthy donors were included in this study. Plasma IL-6 and sIL-6R levels were measured by enzyme-linked immunosorbent assay (ELISA); the frequency of CD4+ IL-6R+ T cells was detected by flow cytometry analysis.ResultsOur data showed a significant increase in plasma sIL-6R levels and the frequency of CD4+ IL-6R+ T cells in peripheral blood in CHB patients compared to asymptomatic carriers and healthy controls (both p<0.05). The elevated prevalence of CD4+ IL-6R+ T cells was positively associated with increased serum alanine aminotransferase levels in CHB patients (r = 0.316, p = 0.007), but was not correlated with serum hepatitis B virus (HBV) DNA load. Moreover, CHB patients with an HBV DNA load >1.0×106 copies/ml had a lower level of plasma sIL-6R than those with an HBV DNA load <1.0×106 copies/ml.ConclusionsCirculating sIL-6R and CD4+ IL-6R+ T cells were increased in CHB patients. Elevated plasma sIL-6R is probably associated with HBV elimination, and CD4+ IL-6R+ T cells in peripheral blood might contribute to the pathogenesis of liver injury in CHB patients

MOLECULAR IDENTIFICATION OF ORIGINAL PLANTS OF FRITILLARIAE CIRRHOSAE BULBUS, ATRADTIONAL CHINESE MEDICINE (TCM) USING PLANT DNA BARCODING

Background: DNA barcoding is a widely used tool that enables rapid and accurate identification of species based on standardized DNA regions. Materials and Methods: In this study, potential DNA barcodes, namely three plastid regions (rbcL, trnH-psbA and matK) and one nuclear ribosomal internal transcribed spacer (ITS) were adopted for species identification of original plants of Fritillariae Cirrhosae Bulbus. Results: The rbcL and trnH-psbA regions showed better success rate of PCR amplification and DNA sequencing, as well as superior discriminatory ability. On the contrary, ITS region did not possess effective genetic variation and matK was faced with low success rate of sequencing. Combination of multi-loci sequences could improve identification ability of DNA barcoding. The trnH-psbA + rbcL could discriminate 25% - 100% species based on the Blast, Tree-Building and Distance methods. Conclusion: The potential DNA barcodes could not completely solving species identification of botanic origins of Fritillariae Cirrhosae Bulbus. In future, we should pay more attention to super-barcoding or specific barcode that enhance ability to discriminate the closely related plants

Motion of phase boundary during antiferroelectric–ferroelectric transition in a PbZrO3-based ceramic

The in situ biasing transmission electron microscopy technique is employed to investigate the nucleation and growth of the ferroelectric phase during the electric field-induced phase transition in Pb0.99{Nb0.02[(Zr0.57Sn0.43)0.94Ti0.06]0.98}O3, a PbZrO3-based antiferroelectric ceramic. The first-order displacive phase transition is found to be highly reversible with the initial antiferroelectric domain configuration almost completely recovered upon removal of the applied field. In the forward transition from the antiferroelectric to ferroelectric phase, {100}c facets are dominant on the phase boundary; while in the reverse transition from the ferroelectric to antiferroelectric phase during bias unloading, the phase boundary is segmented into {101}c and {121}c facets. The motion of the phase boundary is nonuniform, taking the form of sequential sweeping of facet segments. The elastic distortion energy and the depolarization energy at the antiferroelectric/ferroelectric phase boundary is suggested to dictate the facet motion

Elevated IL-6 Receptor Expression on CD4+ T Cells contributes to the increased Th17 Responses in patients with Chronic Hepatitis B

<p>Abstract</p> <p>Background</p> <p>Increased numbers of Interleukin-17-producing CD4⁺T cells (Th17) have been found in association with hepatitis B virus (HBV)-induced liver injury. However, the mechanism underlying the increase of Th17 responses in patients with HBV infection remains unclear. In this study, we investigate the possible regulatory mechanisms of increased Th17 responses in patients with chronic hepatitis B(CHB).</p> <p>Methods</p> <p>Th17 response and IL-6R expression on CD4⁺T cells in peripheral blood samples were determined by flow cytometry. Cytokines TGF-β, IL-1β, IL-6 and IL-17 in plasma and/or supernatant samples were determined by ELISA and the IL-17 and IL-6R mRNA levels were quantified by quantitative real-time reverse polymerase chain reaction.</p> <p>Results</p> <p>All these data indicated that the frequency of periphery Th17 cells is significantly correlated with the percentage of CD4<b>⁺</b>T cells expressing IL-6R in CHB patients. CD4⁺T cells from patients with CHB, but not those from healthy donors, produced higher levels of IL-17 and had more IL-6R expression upon stimulation with the HBV core antigen (HBcAg) in vitro. The PMA/ionomycin and HBcAg -stimulated up-regulation of IL-17 production by CD4⁺T cells could be reversed by a neutralizing antibody against IL-6R.</p> <p>Conclusion</p> <p>we showed that enhancement of IL-6R expression on CD4⁺T cells upon HBV infection contributes to increased Th17 response in patients with CHB.</p

Inhibition of HIF-1α Reduced Blood Brain Barrier Damage by Regulating MMP-2 and VEGF During Acute Cerebral Ischemia

Increase of blood brain barrier (BBB) permeability after acute ischemia stroke is a predictor to intracerebral hemorrhage transformation (HT) for tissue plasminogen activator (tPA) thrombolysis and post-endovascular treatment. Previous studies showed that 2-h ischemia induced damage of BBB integrity and matrix metalloproteinase-2 (MMP-2) made major contribution to this disruption. A recent study showed that blocking β2-adrenergic receptor (β2-AR) alleviated ischemia-induced BBB injury by reducing hypoxia-inducible factor-1 alpha (HIF-1α) level. In this study, we sought to investigate the interaction of HIF-1α with MMP-2 and vascular endothelial growth factor (VEGF) in BBB injury after acute ischemia stroke. Rat suture middle cerebral artery occlusion (MCAO) model was used to mimic ischemia condition. Our results showed that ischemia produced BBB damage and MMP-2/9 upregulation was colocalized with Rhodamine-dextran leakage. Pretreatment with YC-1, a HIF-1α inhibitor, alleviated 2-h ischemia-induced BBB injury significantly accompanied by decrease of MMP-2 upregulation. In addition, YC-1 also prevented VEGF-induced BBB damage. Of note, VEGF was shown to be colocalized with neurons but not astrocytes. Taken together, BBB damage was reduced by inhibition of interaction of HIF-1α with MMP-2 and VEGF during acute cerebral ischemia. These findings provide mechanisms underlying BBB damage after acute ischemia stroke and may help reduce thrombolysis- and post-endovascular treatment-related cerebral hemorrhage

Allele-specific induction of IL-1beta expression by C/EBPbeta and PU.1 contributes to increased tuberculosis susceptibility

Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes, from long-term latent infection to different manifestations of progressive disease. Pro-inflammatory pathways, such as those controlled by IL-1beta, have the contrasting potential both to prevent disease by restricting bacterial replication, and to promote disease by inflicting tissue damage. Thus, the ultimate contribution of individual inflammatory pathways to the outcome of M. tuberculosis infection remains ambiguous. In this study, we identified a naturally-occurring polymorphism in the human IL1B promoter region, which alters the association of the C/EBPbeta and PU.1 transcription factors and controls Mtb-induced IL-1beta production. The high-IL-1beta expressing genotype was associated with the development of active tuberculosis, the severity of pulmonary disease and poor treatment outcome in TB patients. Higher IL-1beta expression did not suppress the activity of IFN-gamma-producing T cells, but instead correlated with neutrophil accumulation in the lung. These observations support a specific role for IL-1beta and granulocytic inflammation as a driver of TB disease progression in humans, and suggest novel strategies for the prevention and treatment of tuberculosis

T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells

Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62LhighCD44low Sca-1+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells. © 2013 Li et al