Down-regulation of human leukocyte antigens class I on peripheral T lymphocytes and NK cells from subjects in region of high-incidence gastrointestinal tumor / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Many types of human tumors can suppress the immune system to enhance their survival. Loss or down-regulation of human leukocyte antigens (HLA) class I on tumors is considered to be a major mechanism of tumor immune escape. Our previous studies found that HLA class I on peripheral-blood mononuclear cells was significantly lower in gastric cancer patients. The present study made an analysis of HLA class I expression on peripheral-blood T lymphocytes and NK cells from subjects of Lijiadian village, a village with high-incidence gastrointestinal tumor.</p><p><b>METHODS</b>A total of 181 villagers from Lijiadian village and 153 normal controls from the Department of Health Examination Center were enrolled in this study. Using a multi-tumor markers detection system, these villagers were divided into two groups: high-risk group (tumor markers positive group) and low-risk group (tumor markers negative group). The percentage of T lymphocytes and NK cells and levels of HLA class I on their surface were determined in these subjects by flow cytometry.</p><p><b>RESULTS</b>Percentages of T lymphocytes and NK cells in peripheral-blood mononuclear cells did not vary with age. The expression level of HLA class I on peripheral T lymphocytes and NK cells was not affected by age or gender, but was significantly down-regulated in Lijiadian villagers (P < 0.05), especially on the surface of NK cells (P < 0.01). Compared with the low-risk group, there was a significant reduction of HLA class I on peripheral T lymphocytes (P < 0.05) and NK cells (P < 0.05) in the high-risk group.</p><p><b>CONCLUSIONS</b>HLA class I on peripheral T lymphocytes and NK cells may be involved in tumorigenesis and development of gastrointestinal tumor, and understanding their changes in expression may provide new insights into the mechanism of tumor immunity.</p>

Modulation of NRF2 and UGT1A expression by epigallocatechin-3-gallate in colon cancer cells and BALB/c mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Green tea is an important source of flavonoids in human diets and epidemiological data correlate green tea consumption with a reduced cancer risk. Given its complicated properties at effective concentrations, we put epigallocatechin-3-gallate (EGCG) that previously reported on its anti-proliferative activities against several cancer cell lines on our research agenda to further examine the mechanism of its chemopreventive potential.</p><p><b>METHODS</b>RNA interference (RNAi) expression vector pSilencer 3.1-H1 was used to construct recombinant nuclear factor erythroid 2 related factor 2 (Nrf2)-targeting RNAi plasmids. EGCG (5 microg/ml) was added into the culture fluid of cells before and after transfection. RT-PCR and Western blotting were used to detect the expression of uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A in cells. Forty male BALB/c mice were assigned to four groups: a normal unexposed control and three groups treated with varying doses of EGCG. Four weeks later, the mice were sacrificed, and their colon tissues were subjected to mRNA and protein expression of Nrf2 and UGT1A via RT-PCR and Western blotting analysis.</p><p><b>RESULTS</b>EGCG up-regulated the expression of Nrf2 and increased the level of UGT1A in cells. The blockade of Nrf2 activity via RNA intervention largely attenuated the induction of UGT1A expression by EGCG. In mice, the mRNA and protein levels of Nrf2 and UGT1A detected by RT-PCR and Western blotting increased (both P < 0.05 compared with the control). This increase in Nrf2 expression also had a positive correlation with an increased UGT1A expression.</p><p><b>CONCLUSIONS</b>EGCG mediated its effect in part by inducing the NRF2 signaling pathway and increasing UGT1A expression. Both in vitro and in vivo studies demonstrated the role of NRF2 and UGT1A expression in the potential use of EGCG as a possible chemopreventive agent and supported further study of EGCG for cancer treatment.</p>

Anti-tumor effects of polybutylcyanoacrylate nanoparticles of diallyl trisulfide on orthotopic transplantation tumor model of hepatocellular carcinoma in BALB/c nude mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatocellular carcinoma (HCC) ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide (DATS) is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide (DATS-PBCA-NP) on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice.</p><p><b>METHODS</b>DATS-PBCA-NP were detected by transmission electron microscope (TEM) and high-performance liquid chromatography (HPLC). The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models (n = 29) were divided into 4 groups: normal saline (NS), empty nanoparticles (EN), DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism.</p><p><b>RESULTS</b>DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice (compared with the other three groups, all P < 0.05) without causing weight loss (P > 0.05). TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice exhibited a markedly higher apoptotic index compared with control tumors. Western blot analysis of tumor tissue revealed that the down-regulated expression of proliferation cell nuclear antigen (PCNA) and Bcl-2 proteins in DATS-PBCA-NP group, and there were no significant differences in the expression of Fas, FasL and Bax proteins among the four groups (P > 0.05).</p><p><b>CONCLUSIONS</b>DATS-PBCA-NP has good prolonged release effect in vivo and hepatic-targeted activity, and significant anti-tumor effect on the orthotopic transplantation HCC model in mice in association with the suppression of proliferation and the induction of apoptosis of tumor cells. These advantages are probably due to their liver targeting characteristics and consequently bring a higher anti-tumor activity.</p>

Determination of the aortic pulse wave velocity in 545 healthy subjects / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the aortic pulse wave velocity (PWV) in mid-aged and elderly populations and to study the correlation between gender and PWV and the tendency of PWV on different age groups.</p><p><b>METHODS</b>According to the clinical trial guideline, we selected 545 healthy subjects (age, 31-85 years, 395 men and 150 women), and measured carotid-femoral PWV, using Complior.</p><p><b>RESULTS</b>The average value of PWV in Chinese healthy subjects was 11.62 +/- 2.97 m/s. There was no significant difference in the PWV values between males and females who were older than 40 years, but the values of PWV were lower in females than in males in the 30-39 year-old group. PWV was positively correlated with age. In the present study, the reference values of PWV were established in the different age groups, based on the regression equations between PWV and age.</p><p><b>CONCLUSION</b>Aortic pulse wave velocity seemed to be influenced by age but hardly influenced by gender in healthy subjects, so that the reference value of PWV should be established according to the different age groups. When aorta got stiffer, the value PWV got larger accordingly when age was increasing.</p>

Clinical study of the distensibility of large arteries in elderly patients with essential hypertension / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the change in the distensibility of large arteries and its influencing factors in elderly patients with essential hypertension.</p><p><b>METHODS</b>Automatic measuring system for pulse wave velocity (PWV) was applied to examine carotid-femoral PWV as an index reflecting distensibility of large arteries. 118 hypertensive patients aged 64 - 83 (mean age 67.12 +/- 10.26) years were included in the study. Of them, 87 were males and 31 were females.</p><p><b>RESULTS</b>PWV of 118 hypertensive patients increased with increasing age (P < 0.001). Multivariate regressive analysis demonstrated that age and systolic blood pressure had the close relationship with PWV (P < 0.001).</p><p><b>CONCLUSION</b>Hypertension of the elderly could cause reduction of distensibility of large arteries. Age and systolic blood pressure had the close relationship with distensibility of large arteries in elderly patients with essential hypertension.</p>