CAPE suppresses migration and invasion of prostate cancer cells via activation of non-canonical Wnt signaling.

Prostate cancer (PCa) was the fifth most common cancer overall in the world. More than 80% of patients died from PCa developed bone metastases. Caffeic acid phenethyl ester (CAPE) is a main bioactive component of honeybee hive propolis. Transwell and wound healing assays demonstrated that CAPE treatment suppressed the migration and invasion of PC-3 and DU-145 PCa cells. Gelatin zymography and Western blotting indicated that CAPE treatment reduced the abundance and activity of MMP-9 and MMP-2. Analysis using Micro-Western Array (MWA), a high-throughput antibody-based proteomics platform with 264 antibodies detecting signaling proteins involved in important pathways indicated that CAPE treatment induced receptor tyrosine kinase-like orphan receptor 2 (ROR2) in non-canonical Wnt signaling pathway but suppressed abundance of ß-catenin, NF-κB activity, PI3K-Akt signaling, and epithelial-mesenchymal transition (EMT). Overexpression or knockdown of ROR2 suppressed or enhanced cell migration of PC-3 cells, respectively. TCF-LEF promoter binding assay revealed that CAPE treatment reduced canonical Wnt signaling. Intraperitoneal injection of CAPE reduced the metastasis of PC-3 xenografts in tail vein injection nude mice model. Immunohistochemical staining demonstrated that CAPE treatment increased abundance of ROR2 and Wnt5a but decreased protein expression of Ki67, Frizzle 4, NF-κB p65, MMP-9, Snail, ß-catenin, and phosphorylation of IκBα. Clinical evidences suggested that genes affected by CAPE treatment (CTNNB1, RELA, FZD5, DVL3, MAPK9, SNAl1, ROR2, SMAD4, NFKBIA, DUSP6, and PLCB3) correlate with the aggressiveness of PCa. Our study suggested that CAPE may be a potential therapeutic agent for patients with advanced PCa.

Isolation and characterization of an osmotic stress and ABA induced histone deacetylase in Arachis hygogaea.

Histone acetylation, which together with histone methylation regulates gene activity in response to stress, is an important epigenetic modification. There is an increasing research focus on histone acetylation in crops, but there is no information to date in peanut (Arachis hypogaea). We showed that osmotic stress and ABA affect the acetylation of histone H3 loci in peanut seedlings by immunoblotting experiments. Using RNA-seq data for peanut, we found a RPD3/HDA1-like superfamily histone deacetylase (HDAC), termed AhHDA1, whose gene is up-regulated by PEG-induced water limitation and ABA signaling. We isolated and characterized AhHDA1 from A. hypogaea, showing that AhHDA1 is very similar to an Arabidopsis HDAC (AtHDA6) and, in recombinant form, possesses HDAC activity. To understand whether and how osmotic stress and ABA mediate the peanut stress response by epigenetics, the expression of AhHDA1 and stress-responsive genes following treatment with PEG, ABA, and the specific HDAC inhibitor trichostatin A (TSA) were analyzed. AhHDA1 transcript levels were enhanced by all three treatments, as was expression of peanut transcription factor genes, indicating that AhHDA1 might be involved in the epigenetic regulation of stress resistance genes that comprise the responses to osmotic stress and ABA.

Elevation of soluble guanylate cyclase suppresses proliferation and survival of human breast cancer cells.

Nitric oxide (NO) is an essential signaling molecule in biological systems. Soluble guanylate cyclase (sGC), composing of α1 and ß1 subunit, is the receptor for NO. Using radioimmunoassay, we discovered that activation of sGC by treatment with bradykinin or sodium nitroprusside (SNP) is impaired in MCF-7 and MDA-MB-231 breast cancer cells as compared to normal breast epithelial 184A1 cells. The 184A1 cells expressed both sGC α1 and sGCß1 mRNAs. However, levels of sGCß1 mRNAs were relatively lower in MCF-7 cells while both mRNA of sGC subunits were absent in MDA-MB-231 cells. Treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) increased mRNA levels of both sGCα1 and sGCß1 in MDA-MB-231 cells but only sGCß1 mRNAs in MCF-7 cells. The 5-aza-dC treatment increased the SNP-induced cGMP production in MCF-7 and MDA-MB-231, but not in 184A1 cells. Bisulfite sequencing revealed that the promoter of sGCα1 in MDA-MB-231 cells and promoter of sGCß1 in MCF-7 cells were methylated. Promoter hypermethylation of sGCα1 and sGCß1 was found in 1 out of 10 breast cancer patients. Over-expression of both sGC subunits in MDA-MB-231 cells induced apoptosis and growth inhibition in vitro as well as reduced tumor incidence and tumor growth rate of MDA-MB-231 xenografts in nude mice. Elevation of sGC reduced protein abundance of Bcl-2, Bcl-xL, Cdc2, Cdc25A, Cyclin B1, Cyclin D1, Cdk6, c-Myc, and Skp2 while increased protein expression of p53. Our study demonstrated that down-regulation of sGC, partially due to promoter methylation, provides growth and survival advantage in human breast cancer cells.

A retrospective cohort study on the natural history of AIDS caused by blood transfusion / 中华流行病学杂志

Objective To study the natural history of AIDS,caused by blood transfusion.Methods All HIV infections and AIDS patients were from Hebei province,including those infected through blood transfusion around 1995,that were identified as through general census of former commercial plasma donors (FCPDs).Among those objects being observed during the incubation period,354 had HIV infections( including 142 cases infected via plasmapheresis and 212 cases caused by transfusion) but had not been treated by HAART before the onset of disease.Objects being observed during the survival period,141 were AIDS patients (including 57 cases infected via plasmapheresis and 84 cases causes by transfusion) but had not been treated by HAART before and after the onset of disease.All infectors and AIDS patients were under follow-up on the progress of illness or death,respectively.Results By December 31,2010,the cumulative incidence among HIV infections was 88.70％ ( 314/354),with the incidence density as 9.14/100 person-years ( 314/3435.75 )and the median incubation period was 113 months.Of 142 HIV infections in the blood donation group and 212 infections in the blood transfusion group,the incubation periods were 112 months and 115 months,respectively.All of the 141 patients died 34 months after the onset,with the death-strength as 204.70/100 person-years (141/68.88) and the period of survival was 4 months.Among those 57 FCPDs infections,they were all died 24 months after the onset,with the death-strength as 250.66/100 person-years (57/22.74) and the survival was 3 months.The other 84 infections who were blood recipients,all died 34 months after the onset,with the death-strength as 182.05/100 person-years (84/ 46.14) and the survival was 4 months.Conclusion Through this study,we noticed that the natural history of all the AIDS patients was caused by blood transmission.It was important to evaluate the natural history of HIV epidemics among both FCPDs and blood recipients,occurred before and after 1995.

Retrospective cohort study on period of incubation and survival among former commercial plasma donors infected with HIV in Hebei province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To examine the state of incubation period and survival time of former commercial plasma donors (FCPDs) infected with HIV.</p><p><b>METHODS</b>All objects infected with HIV were from Hebei province and found from general investigation for FCPDs in 1995. The infector cohort by 142 cases was used to estimate incubation period. In the infector cohort, the time which infectors entered the cohort was their infection time, which was the middle value of the origin date, which was January 1, 1995. The onset of AIDS was defined as an outcome event. End point of observation was Dec 31, 2010. There were 192 months in all from beginning to end. The AIDS cohort by 57 cases was used to estimate the survival of the patients. In the patient cohort, the time of AIDS onset was defined as the time entering the cohort, and death of AIDS was defined as an outcome event. The cumulative incidence ratio, cumulative mortality, illness intensity and mortality intensity were analyzed through Kaplan-Meier.</p><p><b>RESULTS</b>During the observation period, 123 cases of 142 infectors developed into AIDS, the cumulative incidence was 86.42% (123/142) and the intensity was 8.53/100 person-years and the median time of incubation period was 112.0 months (95%CI: 108.8 - 115.2). The death dates of 57 patients were from 1 to 24 months after onset. The cumulative mortality was 100%, and the intensity was 250.66/100 person-years and the median survival time was 3.0 months (95%CI: 1.8 - 4.2). It was estimated that the median time was 115.0 months (9.6 years) from infection to death.</p><p><b>CONCLUSION</b>The median times of incubation and median survival time were 112.0 and 3.0 months, respectively.</p>

Comparative study on the effect of highly active antiretroviral therapy (HAART) in patients with HIV infection acquired by blood transfusion and paid plasma donation / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the effect of HAART in patients with AIDS acquire by blood transfusion and paid plasma donation.</p><p><b>METHODS</b>All AIDS patients whose disease was caused by blood transfusion and commercial plasma donation came from the domicile of Hebei Province. In the group of cases of blood transfusion in whom the infection was caused by one-time blood transfusion before and after 1995, there were 189 cases, of whom 105 cases on HAART were designated as observation group, and 84 cases who were not on HAART were designated as control group. The group of AIDS patients who were former commercial plasma donors (FCPDs) had 120 patients who were identified in the survey of 1995, of whom 63 cases on HAART were designated as observation group and 57 cases who were not on HAART were as control group. Onset dates were defined as the dates into the queue. Death due to AIDS was regarded as an outcome event. Subjects who were enrolled into the observation group and control group were epidemiologically followed up regularly. Observation was ended on December 31, 2010.</p><p><b>RESULTS</b>Mortality of patients after HAART from groups of FCPDs and blood recipients were 4.42/100 person-years and 6.13/100 person-years, respectively. The survival rates of HAART groups were 80% in FCPDs for 110 months and 72% in blood recipients for 90 months, respectively. Meanwhile the mortality of no HAART groups were 182.05/100 person-years and 250.66/100 person-years, respectively. Mean survival of patients whose disease was caused by plasma donation and blood transfusion were 4 months and 3 months, respectively.</p><p><b>CONCLUSIONS</b>Whether the HIV infection was caused by plasmapheresis or blood transfusion, the effects of HAART did not show difference. HAART cold reduce the death intensity and prolong survival.</p>

Retrospective cohort study on the rate of mother-to-child transmission among mothers infected with human immunodeficiency virus type 1 through blood transfusion / 中华流行病学杂志

Objective To study the rate of mother-to-child transmission (MTCT) on HIV-1. Methods All local residents from 8 townships in a region were screened for mothers who had a history of only one blood transfusion and 63 were found HIV-1 positive. A further study on these HIV-1 positive mothers and their children was conducted with the emphasis on the date of receiving blood transfusion, date and type of nationality, history regarding breastfeeding and so on. Sera specimens from 84 children born from 63 HIV-1 positive mothers were screened, using ELISA for HIV-1 antibody, and positive specimens were confirmed by Western-blot. Results The rate of MTCT was 32.1% (27/84) for children with all risk factors related to MTCT. Another 36.8% (7/19) were related to factors on intrauterine, intrapartum and breastfeeding, 35.7% (5/14) to intrapartum and breastfeeding factors, 14.3% (2/14) to intrauterine and intrapartum factors, 37.9% (11/29) to breastfeeding factor alone. By group combination analysis, the MTCT rate was 36.9% (24/65) with breastfeeding, 11.8% (2/17) with artificial feeding, and the former was significantly higher than the latter. Conclusion HIV-1 MTCT rate among mothers caused by a single blood transfusion varied with different risk factors. Breastfeeding played an important role in MTCT, appeared in our study.

Investigation on status of HIV-1 infection among blood recipients from 1994 to 1998 in certain areas of China / 中华流行病学杂志

Objective To study the infection status of HIV-1 among blood recipients from 1994 to 1998 in certain areas of Hebei province. Methods A general investigation was set up among all the people in 15 townships of certain areas from November 2003 to February 2005. An epidemiological investigation was conducted among people who had received blood from donors, during 1994 and 1998. Blood samples were collected. ELISA was used in preliminary screening and Western-blot (WB) was used among people who showed a positive result in the preliminary screening. Results The infection rate of HIV-1 after blood receipt was 15.54% (92/592) , and the infected persons were all appeared in five medical centers of 6 townships which located at the west part of the area. HIV-1 infection happened over the years, and reaching the zenith in the year 1995. Most of the infected persons were young women. Procreation was the main cause of blood transfusion for women and trauma was for men. Conclusion A typical HIV outbreak happened in certain areas after blood transfusion in Hebei.

Following surveillance on HIV infection after blood transfusion / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study epidemiological features of HIV infection after blood transfusion and the situation of transmission among members of family.</p><p><b>METHODS</b>The persons infected with HIV through blood transfusion and their intrafamilial transmission in some city were analyzed and testing methods of ELISA, Western-blot, RT-PCR and subtype analyzing were used. The whole surveillance data came from residents investigation around problem medical centres and HIV monitoring network around Hebei province.</p><p><b>RESULTS</b>173 people infected with HIV after blood transfusion in some city, including 89 cases found in hospital and 84 cases in CDC, accounted for 68.7% (173/252) of all of infected persons by blood transfusion in Hebei province. The rate of intrafamilial transmission, spousal transmission and mother-to-child transmission((MTCT) were 32.0% (49/153),17.0% (26/153) and 32.7% (32/98), respectively. Most of persons infected with HIV were youth among who the female were more than the male. Childbearing and women's ailments were the main cause of blood transfusion from 1990 to 1999, and traumatism surgery took second place. Infected persons by HIV blood, whose time to diagnostic were the year from 1999 to 2009, spread over Kangtai hospital and other hospital which accounted for 45.1% (78/173) and 42.2% (73/173), respectively. The genetype of all patients were B' subtype.</p><p><b>CONCLUSION</b>The medical centers at the grass-roots level in some city resulted in outbreak of infected persons by HIV blood because of having no screening test antibody of HIV for liid blood donors.</p>