Protective effects of protocatechuic acid on growth performance, intestinal barrier and antioxidant capacity in broilers challenged with lipopolysaccharide.

'Prohibition of the antibiotic uses' aggravates the problem of intestinal diseases in poultry, and nutritional regulation has become a research hotspot, such as supplementation with active ingredients derived from plants. This research was conducted to investigate the effects of protocatechuic acid (PCA) on growth, intestinal barrier, and antioxidant capacity of broilers injected with lipopolysaccharide (LPS). Four hundred and eighty 1-day-old yellow feather broilers were randomly allocated to four groups, each with six replicates of 20 broilers. The treatments were basal diet + saline injection (CON) or LPS injection (CON-LPS), and diets with 300 or 600 mg/kg PCA supplementation + LPS injection (P300, P600). Birds were injected intramuscularly on 17th and 19th day of age, then sampled on day 21. The LPS injection significantly decreased BW and average daily gain of broilers, and compared with birds in CON-LPS, PCA supplementation increased (P < 0.05) those variables; moreover, 300 mg/kg PCA also decreased the feed-to-gain ratio. No differences were observed in relative weights of immune organs (P > 0.05). LPS decreased the villus height/crypt depth ratio (V/C) in jejunum of broilers, while PCA (P300 and P600) increased (P < 0.05) the jejunal villus height and V/C compared with birds in CON-LPS. LPS challenge increased jejunal malondialdehyde (MDA) concentration and decreased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities in plasma (P < 0.05); compared with birds in CON-LPS, jejunal and plasmal GSH-Px activity (P300 and P600) and jejunal T-SOD activity (P300) were decreased (P < 0.05), and hepatic MDA concentration (P600) was increased (P < 0.05). LPS significantly decreased the transcript abundances of OCLN, ZO-1, JAM2, MUC2, SOD1, CAT and GPX in jejunal mucosa of birds, and supplementation with PCA attenuated the decrease in OCLN, JAM2, and MUC2 expression compared with birds in CON-LPS; moreover, 600 mg/kg PCA offset the deduction in SOD1, CAT and GPX expression. In conclusion, dietary supplementation with PCA could improve antioxidant status and attenuate the damage in intestinal barrier and loss in growth performance of LPS-challenged broilers, and 600 mg/kg PCA showed more improved effects on antioxidant capacity.

[Investigation of occupational noise exposure and hearing loss among automobile manufacturing workers].

Objective: To investigation the situation of occupational noise exposure and hearing loss among workers in automobile manufacturing enterprise during 2017-2019 in Wuhan. Methods: Workers in automobile manufacturing who underwent physical examination in Wuhan Hospital for the Prevention and Treatment of Occupational Diseases from 2017 to 2019 were included as subjects in the cross-sectional survey. Questionnaire survey, noise detection and pure tone threshold test were used. Excluding individuals with working time less than 3 years and information deficiency, 3 948 individuals were finally included in the study. Results: Among 3 948 workers, 128 workers had hearing loss and the rate of hearing loss was 3.24%, among which 101 workers had high-frequency hearing loss and 27 workers were diagnosed as occupational noise deafness. The prevalence of hearing loss among workers previously exposed to noise was significantly higher than that without prior exposure (12.10%, 0.96%, P<0.05) . The prevalence of hearing loss among workers with occupational noise exposure <80 dB (A) , 80~<85 dB (A) and ≥85 dB (A) was 1.83%, 2.69% and 5.09%, respectively. The prevalence of high frequency hearing loss was 1.60%, 2.05% and 3.71%, respectively. The prevalence of occupational noise deafness was 0.23%, 0.64% and 1.38%, respectively. The prevalence of hearing loss and high frequency hearing loss among workers exposed to different occupational noise was statistically significant (P<0.05) , while the prevalence of occupational noise deafness was not statistically significant (P>0.05) . There were statistically significant differences in the prevalence of hearing loss (2.88%, 4.45%) and occupational noise deafness (0.46%, 1.41%) between those who used protective equipment and those who did not (P<0.05) . Compared with workers exposed to occupational noise <80 dB (A) , workers exposed to occupational noise ≥85 dB (A) had A 3.16-fold increased risk of hearing loss (OR=3.16, 95%CI: 1.44~6.95, P<0.05) . Compared to workers using hearing protective equipment, the risk of hearing loss (OR=1.96, 95%CI: 1.25~3.06, P<0.05) and occupational noise deafness (OR=3.46, 95%CI: 1.51-7.96, P<0.05) significantly increased among those without using hearing protective equipment. Conclusion: The risk of hearing loss in automobile manufacturing workers is significantly associated with occupational noise exposure and the use of hearing protective equipment. Good hearing protection may reduce the risk of occupational noise-induced hearing loss and occupational noise deafness.

LncRNA HULC alleviates HUVEC inflammation and improves angiogenesis after myocardial infarction through down-regulating miR-29b.

OBJECTIVE: The aim of this study was to investigate the long non-coding RNA (lncRNA) HULC in promoting angiogenesis after myocardial infarction (MI) and to further investigate its possible mechanism. MATERIALS AND METHODS: Twenty-four male Sprague Dawley (SD) rats were randomly divided into two groups, namely, operation group and control group. The rats in the operation group were induced by ligation of the left anterior descending coronary artery, while those in control group received the same surgery without ligating the blood vessels. Seven days after the operation, the myocardial tissues of rats were collected to detect HULC expression by quantitative real-time polymerase chain reaction (RT-PCR). At the same time, the expression of HULC in primary myocardial cells and cardiac microvascular endothelial cells were induced by hypoxia. A hypoxia model was constructed in HUVEC cells, and the effects of HULC were explored by RT-PCR, Western blot Technology (WB), Cell Counting Kit-8 (CCK8) assay, EdU staining, Tube-like structure formation experiments. Thereafter, HULC downstream miRNAs were verified by Luciferase, pull-down, and RNA IP experiments. Similarly, the effects of miR-29b on HUVEC were verified by RT-PCR, WB, CCK8 assay, EdU staining, and tube-like structure formation experiments, respectively. RESULTS: RT-PCR detection results showed that the expression of HULC in myocardial tissues was down-regulated after MI, and the expression of HULC in cardiac microvascular endothelial cells was decreased under hypoxia-induced inflammation. In addition, the overexpression of HULC in HUVEC cells could inhibit the expressions of inflammatory factors (IL-1, IL-6 and IL-8) and promote angiogenesis (increased cell viability, increased tube-like structure formation, and increased cell proliferation). Through Dual-Luciferase reporter gene experiments, it was found that HULC could directly target miR-29b. At the same time, miR-29 overexpression significantly reversed the effects of HULC on cell viability, pro-inflammatory cytokines, and angiogenesis. CONCLUSIONS: LncRNA HULC protects HUVEC cells from hypoxia-induced inflammation damage by interacting with miR-29b and inhibiting its expression, and it can also promote angiogenesis.

[Correlation analysis between Dx-pH monitoring and proton pump inhibitor test in the diagnosis of laryngopharyngeal reflux disease].

Objective: The consistency of 24-hour oropharyngeal Dx-pH monitoring and proton pump inhibitor(PPI) test in the diagnosis of laryngopharyngeal reflux disease (LPRD) was investigated. Methods: Sixty patients with laryngopharyngeal reflux (LPR) related symptoms who had never received PPI treatment were assessed by reflux symptom index (RSI) and reflux finding score (RFS) between October 2017 and October 2018, including 28 males and 38 females, aged from 16 to 72 years, with a medium age of 38 years. Prior to treatment, all patients were evaluated with 24 hours oropharyngeal Dx-pH monitoring(Restech). After empiric therapy with PPI twice-daily for 8 weeks, the efficacy was evaluated according to posttreatment RSI score.The data was analysed with Kruskal-Wallis test, Student Newman Keuls test and consistency check. Results: (1)Among all 60 patients,13 patients (21.7%) had pathologic Ryan score and all resulted responsive to PPI;27 patients (45.0%) with a negative Ryan score were unresponsive to PPI; 20 patients (33.3%) despite a negative Ryan score resulted responsive to PPI therapy. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of Ryan score were 39.4%, 100%, 100% and 57.4% respectively. The Kappa value was 0.369 (P<0.01). (2)Among 34 patients (56.7%) with positive Dx-pH results (24-hour oropharyngeal acid reflux events≥ 3 times), 29 patients were positive and 5 patients were negative in PPI test. Among 26 patients with negative Dx-pH results (24-hour oropharyngeal acid reflux events<3 times), 4 patients were positive and 22 patients were negative in PPI test. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of 24-hour oropharyngeal acid reflux events were 87.9%, 81.5%, 85.3% and 84.6% respectively. The Kappa value was 0.696(P<0.01). Conclusions: There is a positive correlation between 24-hour oropharyngeal Dx-pH monitoring positive results (24-hour oropharyngeal acid reflux events≥3 times) and PPI test in the diagnosis of LPRD. The 24-hour oropharyngeal Dx-pH monitoring can be a promising tool for the diagnosis of suspected LPRD patients, and more sensitive and accurate Dx-pH diagnostic index will be required in the clinic.

[Stratified sampling survey of major human parasitic diseases in Henan province].

Objective: To understand the prevalence of major human parasitic diseases and related factors in Henan province. Methods: This stratified sampling survey was carried out according to the requirement of national survey protocol of major human parasitic diseases, 2014-2015. The prevalence of soil-transmitted helminths infection, taeniasis and intestinal protozoiasis were surveyed in 104 sites selected from 35 counties (districts) and the prevalence of clonorchiasis was surveyed in 62 sites selected from 37 townships. In each survey spot, 250 persons were surveyed. A total of 26 866 persons and 15 893 persons were surveyed. Modified Kato-Katz thick smear was used to detect the eggs of intestinal helminthes. Tube fecal culture was used to identify the species of hookworm. The Enterobius eggs were detected in children aged 3 to 6 years by using adhesive tape. The cyst and trophozoite of intestinal protozoa were examined with physiological saline direct smear method and iodine stain method. Results: The overall infestation rate of intestinal parasites was2.02% in Henan, and the worm infection rate was higher than protozoa infection rate. Fourteen kinds of intestinal parasites were found, including nematode (5 species), trematode (2 species), and protozoan (7 species). The infection rate of Enterobius vermicularis was highest, and Qinba Mountain ecological area had the highest infestation rate of intestinal parasites in 4 ecological areas of Henan. There was no significant difference in intestinal parasite infection rate between males and females (χ(2)=3.630, P=0.057), and the differences in intestinal parasite infection rate among different age groups had significance (χ(2)=124.783, P=0.000 1). The infection rate reached the peak in age group ≤9 years and the major parasite was Enterobius vermicularis. Furthermore the overall human infection rate of parasite showed a downward trend with the increase of educational level of the people (χ(2)=70.969, P=0.000 1), the differences had significance (χ(2)=120.118, P=0.000 1). For different populations, the infection rate of intestinal parasites was highest among preschool children. The infection of intestinal helminth was mainly mild, only 2 severe cases were detected. The infection rate of Clonorchis sinensis in urban residents was only 0.006%. Logistic regression analysis showed that being preschool children (χ(2)=15.765, P=0.000 1) and drinking well water (χ(2)=45.589, P=0.000 1) were the risk factors for intestinal parasite infection, and annual income per capita of farmers was the protective factor against intestinal parasite infection. The infection rates of protozoa and intestinal parasites decreased sharply compared with the results of previous two surveys, and the rate of intestinal helminth infection also dropped sharply compared with the second survey. The numbers of protozoa, helminth and intestinal parasites detected in this survey were all less than the numbers found in the previous two surveys. Conclusions: Compared the results of three surveys in Henan, the infection rate of protozoa and intestinal parasites showed a downward trend. The prevention and treatment of Enterobius vermicularis infection in children should be the key point of parasitic disease control in the future.

Effects of N-carbamylglutamate and L-arginine on gonadotrophin-releasing hormone (GnRH) gene expression and secretion in GT1-7 cells.

Recent studies have shown that N-carbamylglutamate (NCG) and arginine (ARG) supplementation improves reproductive performance in livestock. The objectives of the present study were to evaluate the effects of NCG and ARG on GT1-7 cell gonadotrophin-releasing hormone (GnRH) secretion, gene expression and cell proliferation. GT1-7 cells were treated in vitro with different concentrations of NCG (0-1.0mM) or ARG (0-4.0mM) in serum-free medium for 12 or 24h. For GnRH secretion and cell proliferation, GT1-7 cells were more sensitive to NCG than ARG. NCG treatment after 12h increased cell numbers and inhibited GnRH secretion in a dose-dependent manner (P<0.05), although there was no significant effect of NCG on these parameters after 24h culture. ARG treatment decreased GnRH secretion after 24h (P<0.05), whereas it had no effect after 12h. GT1-7 cells express GnRH, Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), neuronal nitric oxide synthase (nNOS) and estrogen receptor α (ERα) genes. High concentrations of NCG (1.0mM) and ARG (4.0mM) inhibited (P<0.05) GnRH and nNOS mRNA abundance in GT1-7 cells. ARG treatment decreased Kiss1 and increased ERα mRNA abundance. Thus, high concentrations of NCG (1.0mM) and ARG (4.0mM) may act both directly and indirectly to regulate GnRH neuron function by downregulating genes related to GnRH synthesis and secretion to slow GnRH production while stimulating GT1-7 cell proliferation.

[Correlation between social support and quality of life in patients with breast cancer at different periods of treatment].

Objective: To analyze the differences between the social support for breast cancer patients and healthy female, and to explore the correlation between social support and quality of life (QOL) in the patients. Methods: From January 2013 to December 2014, 101 patients with operable breast cancer treated at Xinyu City People's Hospital were recruited as the experimental group. They completed questionnaires in the preoperative, postoperative chemoradiotherapy and rehabilitation periods, respectively.101 healthy female volunteers recruited from the community were included as control group, whose age and level of education were matched with those of the experimental group.The general questionnaire including basic information, disease conditions and other projects, perceived social support scale (PSSS), quality of life of breast cancer patients (FACT-B) were applied to evaluate the general situation, social support and QOL of the subjects. The differences in PSSS scores between the experimental and control groups were compared. The correlation between PSSS score and FACT-B score in the experimental group was analyzed. SPSS 18.0 software was used for statistical analysis. Results: The general situations of the experimental and control groups were comparable (all P>0.05). The rates of the total social support score ≥50 in the experimental and control groups were not significantly different (93.6% vs. 94.7%, P=0.067). Compared with that of the control group (23.2±4.8), the scores of family support in the experimental group in preoperative, postoperative chemoradiotherapy and rehabilitation periods were statistically higher (25.6±3.2, 24.2±4.2 and 24.0±3.4, respectively, P=0.034). The social support scores of patients with different demographic characteristics were different. Among the demographic characteristics, years of education and place of residence had the largest impact. The scores of social support in patients with longer education years and living in the urban area were higher than those with shorter education years and living in the rural areas (P<0.001). The scores of QOL among preoperative, postoperative chemoradiotherapy and rehabilitation periods in the experimental group were significantly different (all P<0.05). The patients gained the highest score of QOL in the preoperative period (110.7±5.1) and the lowest in the postoperative chemoradiotherapy period (95.3±18.1). The QOL of patients in the experimental group in preoperative, postoperative chemoradiotherapy and rehabilitation periods were all positively correlated with the overall social support (all P<0.01). Conclusions: The QOL of breast cancer patients at different periods of treatment is positively correlated with the social support. The quality of life can be enhanced by improving the social support for the patients.

[Effect of exendin-4 on lipid deposition in skeletal muscle of diet-induced obese mice and its underlying mechanism].

Objective: To investigate the effect of exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, on reducing lipid deposition and improving insulin resistance in skeletal muscle and the underlying mechanisms in high-fat diet (HFD)-induced obese mice. Methods: Twelve male C57BL/6J mice were challenged with HFD for 12 weeks to induce obesity and then randomly divided into two groups: exendin-4 group (intraperitoneal injection of 24 nmol·kg-1·d-1 exendin-4 for 4 weeks) and HFD group (intraperitoneal injection of normal saline for 4 weeks), with 6 mice in each group. Additional 6 mice were also selected as control group. Body weight, fasting blood glucose were recorded. Serum triglyceride (TG), total cholesterol (TC), insulin and skeletal muscle triglyceride levels were measured by enzyme-linked immunosobent assay (ELISA). Oil red O staining was used for morphologic changes of frozen sections from skeletal muscle. The protein levels of lipid metabolic pathway mediated by AMP-activated protein kinase (AMPK) and insulin signailing pathway were determined by Western blot. Results: Compared with mice in HFD group, exendin-4 significantly decreased body weight[(37.68±1.80) vs (46.03±5.00) g, P<0.025], fasting blood glucose[(5.40±0.33) vs (7.65±1.92) mmol/L, P<0.025], serum TG[(37.78±7.14) vs (80.76±34.22) mg/dl, P<0.025], TC[(180.13±18.75) vs (217.57±22.52) mg/dl, P<0.025], insulin[(0.58±0.01) vs (1.67±1.23) ng/ml, P<0.025]and skeletal muscle TG levels[(9.84±1.08) vs (19.35±7.44) mg/g, P<0.025]of obese mice. Oil red O staining revealed that exendin-4 alleviated the accumulation of larger lipid droplets in skeletal muscle. The protein expressions of lipolysis and lipid oxidation mediated by AMPK and insulin signailing pathway were up-regulated, and the protein expressions of lipogenesis mediated by AMPK were down-regulated after intervention of exendin-4. Conclusion: Exendin-4 reduces lipid deposition and insulin resistance in skeletal muscle of HFD-induced obese mice via activating AMPK and up-regulating insulin signailing pathway.

[The clinical study of olfactory dysfunction in IgG4-related disease].

Objective:IgG4-related disease is a newly recognized systemic disease, and its elucidation is progressing. However, little is known about its sinonasal manifestations.The aim of this study was to assess the olfaction of patients with IgG4-related disease.Method:Twenty-two patients with IgG4-related disease underwent the odor stick identification test to measure olfactory function.We analyzed the clinical features, including serum IgG4 levels, involved organs, and sinonasal computed tomography scores to explore the etiology of olfactory dysfunction.Result:Eleven patients with IgG4-related disease were found to have olfactory dysfunction. There were no differences in the clinical features between the olfactory dysfunction group and the normal group.Conclusion:There were no correlation between olfactory function and serum IgG4 level, involved organs or sinonasal computed tomography scores.We found that the prevalence of olfactory dysfunction was high in patients with IgG4-related disease and that it could be reversed.Olfactory dysfunction appears to be a novel important manifestation of IgG4-related disease.

[Effect of umbilical cord mesenchymal stem cell transplantation on immune function and prognosis of patients with decompensated hepatitis B cirrhosis].

Objective: To investigate the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on the immune function and prognosis of patients with decompensated hepatitis B cirrhosis. Methods: A total of 65 patients with decompensated hepatitis B cirrhosis were divided into observation group and control group. The patients in the observation group were given intervention (via the proper hepatic artery or the portal vein) and intravenous infusion of 4×108 hUCMSCs in two doses, as well as the same basic treatment as in the control group. The patients in the control group were given conventional medical treatment. ELISA as used to measure the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), interleukin-10 (IL-10), and transforming growth factor-ß (TGFß) in the observation group before surgery and at 1 week after surgery, as well as the serum levels of IL-6, TNFα, IL-10, and TGFß in the control group on admission and at 1 week after admission. Flow cytometry was used to measure the percentage of lymphocyte subsets in the observation group before surgery and at 1 week after surgery, as well as that in the control group on admission and at 1 week after admission. In addition, the patients' prognosis and major complications during hospitalization were observed in both groups, and the patients were followed up for 24 weeks to record the number of deaths. The t-test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data which were expressed as percentages. Results: At 1 week after the transplantation of hUCMSCs, compared with the control group, the observation group had significant reductions in the serum levels of IL-6 and TNFα and significant increases in the serum levels of IL-10 and TGFß (all P < 0.001), as well as significant increases in the percentages of T4 cells and Treg cells and significant reductions in the percentages of T8 cells and B cells (all P < 0.05). There were no significant differences in the changes in T3 cells and natural killer cells between the two groups (P > 0.05). Compared with the control group, the observation group had a significantly lower probability of progression to liver failure (6.45% vs 14.71%, P = 0.017). Conclusion: In the treatment of patients with decompensated hepatitis B cirrhosis, transplantation of UCMSCs can inhibit the proliferation of T cells and B cells and the differentiation of T8 cells, upregulate Treg cells, promote the secretion of immunosuppressive cytokines, and reduce the production of inflammatory cytokines. Therefore, it can alleviate liver inflammatory response and liver cell damage and reduce the probability of hepatic failure.

In vitro and in vivo antitumor activity of a novel chlorin derivative for photodynamic therapy.

In presented paper, a new chlorin derivative 5,10,15,20-tetrakis[(5-N-morpholino)pentyl] chlorin (TMC) was investigated as a photosensitizer in photodynamic therapy (PDT). Cellular uptake, cytotoxicity, intracellular location, biodistribution and antitumor effects were studied using human esophageal cancer cells (Eca-109) and human cervical cancer cells (Hela) in vitro and an esophageal cancer model in BALB/c nude mice. Cellular uptake and biodistribution of TMC were measured by fluorescence spectrophotometer. Cytotoxicity of TMC against Eca-109 and Hela cells was determined by MTT assay. The intracellular location of TMC was detected with a confocal microscopy. It was showed that TMC could rapidly accumulate in tumor cells and localize in cytoplasm. TMC was found to be low-toxic in dark but extensively photosensitive in vitro. A fast clearance rate of TMC was observed in Eca-109-bearing mice. In particular, TMC could significantly inhibit the tumor growth and exhibit a notable antitumor efficacy for PDT in vivo.

Yeast CUP1 protects HeLa cells against copper-induced stress

As an essential trace element, copper can be toxic in mammalian cells when present in excess. Metallothioneins (MTs) are small, cysteine-rich proteins that avidly bind copper and thus play an important role in detoxification. Yeast CUP1 is a member of the MT gene family. The aim of this study was to determine whether yeast CUP1 could bind copper effectively and protect cells against copper stress. In this study, CUP1 expression was determined by quantitative real-time PCR, and copper content was detected by inductively coupled plasma mass spectrometry. Production of intracellular reactive oxygen species (ROS) was evaluated using the 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assay. Cellular viability was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the cell cycle distribution of CUP1 was analyzed by fluorescence-activated cell sorting. The data indicated that overexpression of yeast CUP1 in HeLa cells played a protective role against copper-induced stress, leading to increased cellular viability (P<0.05) and decreased ROS production (P<0.05). It was also observed that overexpression of yeast CUP1 reduced the percentage of G1 cells and increased the percentage of S cells, which suggested that it contributed to cell viability. We found that overexpression of yeast CUP1 protected HeLa cells against copper stress. These results offer useful data to elucidate the mechanism of the MT gene on copper metabolism in mammalian cells.

Yeast CUP1 protects HeLa cells against copper-induced stress.

As an essential trace element, copper can be toxic in mammalian cells when present in excess. Metallothioneins (MTs) are small, cysteine-rich proteins that avidly bind copper and thus play an important role in detoxification. Yeast CUP1 is a member of the MT gene family. The aim of this study was to determine whether yeast CUP1 could bind copper effectively and protect cells against copper stress. In this study, CUP1 expression was determined by quantitative real-time PCR, and copper content was detected by inductively coupled plasma mass spectrometry. Production of intracellular reactive oxygen species (ROS) was evaluated using the 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assay. Cellular viability was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the cell cycle distribution of CUP1 was analyzed by fluorescence-activated cell sorting. The data indicated that overexpression of yeast CUP1 in HeLa cells played a protective role against copper-induced stress, leading to increased cellular viability (P<0.05) and decreased ROS production (P<0.05). It was also observed that overexpression of yeast CUP1 reduced the percentage of G1 cells and increased the percentage of S cells, which suggested that it contributed to cell viability. We found that overexpression of yeast CUP1 protected HeLa cells against copper stress. These results offer useful data to elucidate the mechanism of the MT gene on copper metabolism in mammalian cells.

Synthesis and biological evaluation of a new angiotensin II receptor antagonist.

The design, synthesis, in vitro and in vivo evaluation of (2 R,6 S)-4-({1-[2-(1 H-tetrazol-5-yl)phenyl]-1 H-indol-4-yl}methyl)-2,6-dimethylmorpholine, compound 1, as a novel angiotensin II receptor antagonist is outlined. Radioligand binding assays showed that 1 displayed a high affinity for the angiotensin II type 1receptor with IC50 value of 0.82 nM. It acted as a potent anti-hypertensive derivative (maximal reduction of mean arterial pressure of 47 mm Hg at 10 mg/kg po in spontaneously hypertensive rat producing a dose-dependent fall in blood pressure following oral administration lasting beyond 10 h. Acute toxicity tests measured the LD50 of 1 value as 2431.7 mg/kg, which is higher than Losartan (LD50=2248 mg/kg). In addition further testing showed that 1 also demonstrated efficient anti-proliferative activity in vitro and anti-prostate cancer activity in vivo were also found. Taken together this compound could be considered as an effective and durable anti-hypertension drug candidate with additional anti-prostate cancer activity. These encouraging results are deserved of further investigation towards its use for therapeutic benefit.

Synthesis, anti-hypertensive effect of a novel angiotensin II AT1 receptor antagonist and its anti-tumor activity in prostate cancer.

Since the first non-peptide Ang II receptor antagonist was originally reported, it has become the most common target in the development of new treatments for hypertension. In recent years, all components of the classical RAS have been reported in the prostate, these results suggest the possibility that ARB is a novel therapeutic class of agents for prostate cancer. In this study, a new compound 2-(4-((2-propyl-5-nitro-1H-benzo[d]imidazol-1-yl) methyl)-1H-indol-1-yl) benzoic acid was synthesized and evaluated as a novel angiotensin II AT1 receptor antagonist by radioligand binding assays, anti-hypertensive assays in vivo and oral acute toxicity test. MTT assays and tests in nude mice were used to demonstrate its anti-tumor activity. This new compound showed high affinity to AT1 receptor and anti-hypertensive activity in spontaneously hypertensive rats and renal hypertensive rats. Moreover, in human prostate cancer cells and in athymic nude mice bearing human prostate cancer cells, we observed this new compound had an efficient antiproliferative activity in vitro and anti-tumor activity in vivo. The preliminary pharmacological characteristics with oral acute toxicity test suggested that this new compound can be considered as a candidate for both anti-hypertensive and anti-tumor drug.

Tunable radiation source by coupling laser-plasma-generated electrons to a periodic structure.

Near-infrared radiation around 1000 nm generated from the interaction of a high-density MeV electron beam, obtained by impinging an intense ultrashort laser pulse on a solid target, with a metal grating is observed experimentally. Theoretical modeling and particle-in-cell simulation suggest that the radiation is caused by the Smith-Purcell mechanism. The results here indicate that tunable terahertz radiation with tens GV/m field strength can be achieved by using appropriate grating parameters.

Histopathology, immunohistochemistry, in situ apoptosis, and ultrastructure characterization of the digestive and lymphoid organs of new type gosling viral enteritis virus experimentally infected gosling.

Here, for the first time, to colocalize new type gosling viral enteritis virus (NGVEV) with histological lesions and in situ apoptosis in the digestive organs (esophagus, proventriculus, gizzard, small intestine, cecum, rectum, liver, and pancreas) and the lymphoid organs (bursa of Fabricius, thymus, Harderian gland, and spleen) of experimentally infected goslings, portions of tissues were collected at sequential infection time points and examined by histopathology for histological lesions, immunohistochemical staining for viral antigens, ultrastructural observation by transmission electron microscope (TEM) for virus particles and apoptotic cells, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay for in situ apoptosis. The hyperemia, hemorrhage, infiltration of lymphocytes, progressive lymphoid depletion, apoptosis, and necrosis were readily observed in the lymphoid organs and intestine tract by histopathological examination. The NGVEV particles and viral antigens widely appeared in the small intestine and bursa of Fabricius as early as 2 d postinfection (PI) by TEM and immunohistochemical staining, and the presence and quantity of it reached a maximum during 6 to 12 d PI. The principal sites for NGVEV were endothelial cells, epithelia, mucosal cells, glandular cells, fibrocytes, macrophages, and lymphocytes. A series of apoptotic morphological changes including chromatin condensation and margination, cytoplasmic shrinkage, and formation of apoptotic body were observed by TEM, and the number of apoptotic cells was largely increased from 4 d PI and peaked at 9 d PI by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling analysis. The histological organ lesions and apoptosis in vivo were generally associated with sites of NGVEV localization, which can be regarded as the cause of death. This work may shed light on the pathogenesis of new type gosling viral enteritis and put new insight into the pathogenesis of goose adenovirus.

Increased expression of paxillin is found in human oesophageal squamous cell carcinoma: a tissue microarray study.

Oesophageal cancer is one of the most common cancers worldwide. Currently, the tumour, node, metastasis (TNM) staging system is the primary method for determining its extent and prognosis, however, data suggest this system does not predict prognosis accurately. Research has, therefore, concentrated on searching for specific biomarkers. Paxillin has been shown to play an important role in controlling cell spread and migration. Its over-expression is considered to correlate with the prognosis of some types of cancers, however, the relationship between paxillin expression and clinical outcome in oesophageal cancer has not been investigated. This study determined the expression of paxillin by immunohistochemistry on the tissue microarray of 100 oesophageal squamous cell cancer patients followed up for a mean of 55 months. Paxillin was over-expressed in tumours in 27/100 cases, compared with 6/100 cases for adjacent non-tumoural cells. No correlation occurred between expression of paxillin and overall patient survival, hence paxillin is not an effective prognostic marker in these patients.