text:
Sunday, August 10, 2008
© Copyright 2015 Gwinnett Daily Post
I read Rob Jenkins' column ("Top 11 reasons not to get a tatoo," Community, July 27) with a great deal of interest and with even more appall and hurt. It surprises me that the Gwinnett Daily Post would allow such a column to appear in its newspaper.I am a well-educated, conservative career woman who happens to have a few tattoos. I got my first one when I was 37, and as they say, "A tattoo is like potato chips. You can't have just one." I got my most recent, my fifth tattoo, at age 55. The first tattoo looks just as good as the last. I guarantee they will look just as good when I am 80, God willing. I am not an alcoholic, nor do I have Hepatitis C. My body IS my temple and I have birthed a wonderful daughter, who, by the way, has three tattoos. I am not a drug addict, depressed nor a tramp. To know this is how (Jenkins) view(s) people who make the choice to mark their bodies is hurtful and extremely judgemental. If you were standing in front of my husband and made these comments, you would not be standing for long. I have acquired my tattoos at reputable parlors here in Georgia and Michigan. I would reccommend these places to anyone interested in permanent body art. I am proud of every single piece I have on my body. Each one holds a personal meaning for me. I suspect, given (Jenkins is a) professor at the local college, (he has) a few students who sport a tattoo or two or three. I would love to be the fly on the wall to hear what kind of feedback (he) will get from them.
More like this story
- To the editor: Jenkins out of line to stereotype all people who have tattoos ( August 10, 2008 )
- JENKINS: Thinking about getting a tattoo? Don't do it ( July 4, 2015 )
- Hog wild: Work 'like Christmas' for local motorcycle artist ( October 14, 2011 )
- It's time for stupid things I've said - the 2008 edition ( December 7, 2008 )
- BOC to consider tattoo regulations ( November 13, 2005 )


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The first two authors contributed equally to this paper.
Cancer Therapy
Human sodium iodide symporter gene adjunctive radiotherapy to enhance the preventive effect of hMUC1 DNA vaccine
Article first published online: 12 JUN 2007
DOI: 10.1002/ijc.22837
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 7, pages 1593–1599, 1 October 2007
Additional Information
How to Cite
Jeon, Y. H., Choi, Y., Kim, H. J., Kim, C. W., Jeong, J. M., Lee, D. S. and Chung, J.-K. (2007), Human sodium iodide symporter gene adjunctive radiotherapy to enhance the preventive effect of hMUC1 DNA vaccine. Int. J. Cancer, 121: 1593–1599. doi: 10.1002/ijc.22837
Publication History
- Issue published online: 24 JUL 2007
- Article first published online: 12 JUN 2007
- Manuscript Accepted: 11 APR 2007
- Manuscript Received: 22 JAN 2007
Funded by
- Cancer Research Center
- Korean Science & Engineering Foundation (KOSEF)
- BK21 Project for Medicine
- Dentistry
- Pharmacy in Korea
- Abstract
- Article
- References
- Cited By
- radioiodine gene therapy;
- immunotherapy;
- CT26/hMUC1-hNIS-Fluc (CMNF);
- hMUC1;
- sodium iodide symporter;
- cancer DNA vaccine
We demonstrate the use of combination therapy to overcome the limitations of cancer DNA vaccines by adding radioiodine gene therapy in an animal cancer model. We established a stable cell line (CT26/hMUC1-hNIS-Fluc: CMNF) expressing the hMUC1, hNIS and Fluc genes using a retro- and lentivirus system. The survival rates (%) of CMNF cells were determined using clonogenic assays after 131I treatment. After i.m. immunization to 4 groups of Balb/c mice (pcDNA3.1, pcDNA3.1+131I, pcDNA3-hMUC1+PBS and pcDNA3-hMUC1+131I groups) with pcDNA3-hMUC1 or pcDNA3.1 once a week for 2 weeks, 1 × 105 CMNF cells were injected s.c. into the right thighs of mice in each group. Twenty-one days after tumor transplantation, 131I was administered i.p. to the pcDNA3.1+131I and pcDNA3-hMUC1+ 131I groups. Tumor progression was monitored in the 4 groups by bioluminescent and scintigraphic imaging and by taking caliper measurements. Tumor masses were extracted and weighted at 39 days post-tumor challenge. We confirmed that CMNF cells highly express hMUC1, hNIS and Fluc by FACS, 125I uptake, and luciferase assay. The survival rates of CMNF were markedly reduced to (14.6 ± 1.5)% after 131I treatment compared with the survival rates of parental cells (p < 0.001). Tumor growth inhibition was significant only in the pcDNA3-hMUC1+ 131I group at 39 days post challenge. Tumor masses in pcDNA3-hMUC1+ 131I group were smaller than those of the other groups. This study shows that the weak preventive effects of cancer DNA vaccine can be overcome by radioiodine gene therapy utilizing sodium iodide symporter. © 2007 Wiley-Liss, Inc.
Cancer DNA vaccines encoding tumor associated antigen represent a novel form of cancer treatment. These vaccines have been found to be an effective means of cancer therapy by several researchers.1, 2, 3, 4 It is relatively easy to devise a cancer DNA vaccine to insert antigen into mammalian expression vector containing CMV promoter, and thus to deliver the required DNA via various routes in living organisms.5, 6 Following the administration of tumor associated antigen encoding cancer DNA vaccine into a living organism, antigen peptide of the cancer DNA vaccine is delivered to immune related cells, and thus immune response against the antigen peptide is induced in the host. Immune systems stimulated by cancer DNA vaccines may protect host from cancer occurrence or recurrence.7 However, cancer DNA vaccines are not always effective because of their limited potencies, regulatory T cells hindrance, cytokine imbalances in the host or others.8, 9, 10, 11
Sodium iodide symporter (NIS) is a specialized active iodide transporter that cotransports sodium and an iodide ion.12, 13, 14 Many researchers have tried to apply this system to cancer gene therapy using viral or nonviral gene systems by directly transferring the NIS gene into living organisms. Moreover, NIS gene expression in cancer cells allows effective radioiodine (131I, 188Re) therapy, which has led to good prognoses in preclinical and clinical models.15, 16, 17 Moreover, some investigators have reported that NIS-specific radioiodine accumulation within NIS-transfected cells can induce significant tumor reduction in athymic nude mice.18, 19, 20, 21
Cancer DNA vaccine researchers have added various genes to cancer DNA vaccines to increase therapeutic effects, and these various gene supplements have resulted in significant tumor regression in living subjects.22, 23, 24, 25 Since radioiodine gene therapy has been shown to be a powerful tool for cancer gene therapy, we attempted to develop a new combination therapy to enhance the preventive effects of cancer DNA vaccines by utilizing a NIS approach. In this study, we attempted to enhance the tumor growth inhibition induced by hMUC1 DNA vaccination by using radioiodine gene therapy of human NIS.
Material and methods
Specific pathogen-free 6-week-old female BALB/c mice were obtained from SLC (Hamamatsu, Japan).26 All experimental animals were housed under specific pathogen-free conditions and were handled in accord with the guidelines issued by the Seoul National University Animal Research Committee.
Generation of cDNA constructs and plasmid preparation
The human pancreatic mucin1 gene, hMUC1 (accession no. J05582), was cloned into the BamHI site of pcDNA3 vector (Invitrogen, Carlsbad, CA). Plasmid DNA was amplified in E. coli DH5α and purified by large-scale plasmid preparation using endotoxin-free Giga Prep columns (QIAGEN, Chatsworth, CA). DNA was dissolved in endotoxin-free TE buffer for storage.
Generation of Lentivirus
To construct hNIS expressing lentiviral vector under the control of ubiquitin C promoter, the hNIS gene was cloned into pLenti6/UbC/V5-DEST (Invitrogen, Carlsbad, CA). Replication-incompetent lentivirus was produced by cotransfecting lentiviral vector carrying hNIS and a ViraPower™ Packaging Mix (Invitrogen, Carlsbad, CA) into 293FT producer cell line. 293FT cells (6 × 106) were transient transfected using 36 μl Lipofectamine 2000 (Invitrogen, Carlsbad, CA) in 10 cm tissue culture plates. Cells were cotransfected with 5 μg of lentiviral vector and 10 μg of packaging plasmids (gag, pol, vsv-g, rev). Growth medium (DMEM containing 10% FBS, and 1% penicillin/streptomycin) was changed at 24 hr post-transfection and lentivirus-containing supernatant was harvested at 48 hr post-transfection. Harvested supernatants were centrifuged at 3,000 rpm for 15 min at 4°C to pellet cell debris and stored at −80°C for later use. To assess the activity of recombinant virus encoding hNIS reporter gene, HT1080 human fibrosarcoma cells were infected by adding thawed lentivirus-supernatant containing 10 μg/ml of Polybrene. Human sodium-iodide symporter (hNIS) expression was confirmed by examining 125I uptake.
Generation of Retrovirus
Firefly luciferase gene under EF-1α promoter was cloned into pMSCVneo (BD Bioscience Clontech, CA). Retrovirus was produced by cotransfection into a human 293FT producer cell line using retroviral vector carrying the luciferase gene and packaging plasmids (gag, pol, vsv-g) (BD Bioscience Clontech, CA). Transient transfection of 293FT cells (6 × 106) was performed using 36 μl of Lipofectamine 2000 (Invitrogen, Carlsbad, CA) in 10 cm tissue culture plates. Cells were cotransfected with 5 μg of retroviral vector and 10 μg of packaging plasmids. Growth media (DMEM containing 10% FBS and 1% penicillin/streptomycin) were changed at 24 hr post-transfection and retrovirus-containing supernatants were harvested at 48 hr post-transfection. Harvested supernatants were centrifuged at 3,000 rpm for 15 min at 4°C to pellet cell debris and stored at −80°C for later use. To assess the activity of recombinant virus encoding firefly-luciferase reporter gene, HT1080 human fibrosarcoma cells were infected by adding thawed retrovirus-containing supernatant and 10 μg/ml of Polybrene. Cell luciferase expression was confirmed by checking luciferase activity using a luminometer (Applied Biosystems, Forster, CA).
Murine tumor cell line expressing hMUC1, hNIS and firefly luciferase
hMUC1 expressing CT26 (CT26/hMUC1) was kindly provided by Dr. Jung-Ah Cho.26 Viral supernatants were transduced into CT26/hMUC1 of the H-2d MHC type. Stable clones (CT26/hMUC1-hNIS-Fluc referred to as CMNF) were also subjected to luciferase assays and 125I uptake using a microplate luminometer (Applied Biosystems, Forster, CA) and gamma counter (GMI, Ramsey, MN).
To examine hMUC1 expressions on CMNF cell surfaces, cells were harvested and suspended in 0.1% BSA-containing PBS. Primary antibodies were added to these suspensions, and anti-MUC1 (Biomeda, CA) mouse antibody was used as the primary antibody.27 After 1 hr incubation on ice, cells were washed and pelleted to remove unbound antibodies. FITC-tagged anti-mouse antibody was used as a secondary antibody and incubated for 30 min on ice. Cold 2% PFA-containing PBS was used to fix the cells, and finally, fluorescence intensities were measured using a Coulter FACScan. FACS analysis showed that CMNF cells highly expressed hMUC1 tumor antigen. In addition, we observed that bioluminescent signals increased with cell numbers.
In vitro clonogenic assay
The procedure used, with minor modifications, has been described previously.28 Briefly, cells were grown in a 75-cm2 flask and incubated for 7 hr at 37°C in 5 ml HBSS containing 37 MBq/10 ml (1 mCi/10 ml) Na131I. The reaction was terminated by removing the radioisotope-containing medium and washing the cells twice with HBSS. The cells were then trypsinized, counted and plated at densities of 250 or 1,000 cells per well in DMEM in 6-well plates. Cells were grown for 10 days, fixed with 3:1 methanol/acetic acid, stained with crystal violet and macroscopic colonies numbers were counted. Survival rates were defined as colony numbers in radionuclide treated plates expressed as percentage of numbers in plates treated with HBSS only.
Monitoring of tumor growth inhibition in living mice
The IVIS200 imaging system (Xenogen, Alameda, CA), which includes an optical CCD camera mounted on a light-tight specimen chamber, was used for data acquisition and analysis. Firefly D-luciferin potassium salt (Fluc substrate), was diluted to 3 mg/100 ul in PBS before use, and mice were injected i.p. with 100 μl of this D-luciferin solution. Mice were placed individually in the specimen chamber containing the CCD camera, and then cooled to −105°C. Light emitted by luciferase in mice was then measured. Gray scale photographic images and bioluminescent color images were superimposed using LIVINGIMAGE V. 2.12 (Xenogen, Alameda, CA) and IGOR image analysis software (WaveMetrics, Lake Oswego, OR). Bioluminescent signals were expressed in units of photons per cm3 per second per steradian (P/cm2/s/sr).
pcDNA3.1 (50 μg/100 μl) or pcDNA3-hMUC1 (50 μg/100 μl) was injected i.m. into quadriceps muscles of right hind legs once a week for 2 weeks. One week after the final immunization, each group was inoculated s.c. with 1 × 105 CMNF cells in right thighs. Mice had received a low-iodine diet and T4 supplementation in their drinking water for 2 weeks post CMNF challenge to maximize radioiodine uptake in tumors and to reduce iodide uptake by thyroid glands. Each animal was administered 111 MBq (3 mCi) of 131I or saline i.p. Mice were repeatedly imaged at 7, 13, 21, 28, 35 days post CMNF challenge using an optical CCD camera to acquire photons, 10 min after injecting D-luciferin. To quantify emitted light, regions of interest were drawn over the tumor region and total photon effluxes over an exposure time of 10 sec were determined. For scintigraphic imaging, 99mTc-pertechnetate was injected i.p and mice were imaged using a γ-ray camera (ON-410) at 21 days postchallenge. Tumor size was measured using a caliper at 17, 21, 28, 32, 39 days and tumor weights were measured at 39 days.
Statistical analysis
Statistical significances were determined using an unpaired Student's t test, and Kaplan Meier curves were generated for survival analysis. The survival curves of 2 groups were compared using the log rank test. P values of <0.05 were considered significant.
Establishment of a cancer cell line expressing high levels of hMUC1, hNIS and firefly luciferase.
To determine hMUC1, hNIS and Fluc gene expressions in selected stable cell lines (CT26/hMUC-hNIS-Fluc, referred to a CMNF), we performed FACS analysis, and luciferase and 125I uptake assays, as shown in Figure 1. FACS analysis showed that stable transfectants highly expressed the hMUC1 gene (Fig. 1a), and bioluminescence signals and 125I uptakes were found to correlate well with cell numbers (Figs. 1b and 1c).
In vitro clonogenic assay
As shown in Figure 2, the survival rates of CT26/hMUC-hNIS-Fluc cells were markedly reduced to (14.6 ± 1.5)% in response to 131I vs. CT26 cells (p < 0.001).
Tumor growth inhibition induced by hMUC1 vaccination plus radioiodine gene therapy
We performed following experimental procedures for radioiodine gene therapy and immunotherapy (Fig. 3). NIS gene expression was observed in all 4 mouse groups (Fig. 4a). Also, we observed tumor growth inhibition induced by hMUC1 vaccination in the two pcDNA3-hMUC1 vaccination groups (pcDNA3-hMUC1+PBS, pcDNA3-hMUC1+131I groups) compared with the two pcDNA3.1 vaccination groups (pcDNA3.1, pcDNA3.1 + 131I groups) by bioluminescent imaging (Fig. 4b). Following 131I treatment to all groups, tumor progression was monitored by bioluminescent imaging and caliper measurements until 39 days postchallenge (Figs. 4b–4d), and a difference in tumor growth inhibition was observed between the pcDNA3-hMUC1 + PBS and pcDNA3-hMUC1 +131I groups at 28 days postchallenge. Significant tumor growth inhibition was observed in the pcDNA3-hMUC1 +131I group vs. the pcDNA3.1 + PBS, pcDNA3.1+131I and pcDNA3-hMUC1+PBS groups (p < 0.05). At 39 days postchallenge, animals were euthanized and tumor masses were removed and weighted. Significant tumor growth inhibition was observed in the pcDNA3-hMUC1 + 131I group vs. the pcDNA3.1, pcDNA3.1+131I and pcDNA3-hMUC1+PBS groups (p < 0.05) (Fig. 4e). As shown in the Kaplan-Meier plots in Figure 4f, 80% of tumor bearing mice survived until 50 days postchallenge in the combination therapy group(pcDNA3-hMUC1 + 131I group) using hMUC1 vaccination + 131I treatment, whereas almost all animals in the other groups died (pcDNA3.1 + PBS, pcDNA3.1+131I and pcDNA3-hMUC1+PBS group: 0, 10, 20 %, respectively).
Immunotherapy using cancer DNA vaccines is now viewed as a means of inhibiting tumor growth in living organisms. Various strategies have been applied to increase the potency of DNA vaccines; for example, targeting tumor-associated antigens to facilitate rapid cellular degradation, directing tumor-associated antigens to chemokines, coinjecting cytokines or coadministering CpG motif.29, 30, 31, 32, 33, 34, 35, 36, 37 However, immunotherapies based on cancer DNA vaccines in combination with these strategies have been found to be ineffective at inhibiting tumor growth. Thus, immunotherapy researchers have tried to utilize other modalities to overcome the preventive (or therapeutic) limitations of cancer DNA vaccines.
Sodium iodide symporter (NIS) has been used for radionuclide gene therapy as an adjunct to treatment in various types of cancer. Some investigators have found that effective gene expression is induced in living subjects by infecting various cancer cells with NIS, and have achieved good therapeutic effects in preclinical models.15, 16 Other reports have shown that NIS gene transfer using tissue-specific promoter allows the targeting of NIS gene expression in specific cancer cells, thereby maximizing tissue-specific cytotoxicities and minimizing toxic side-effects in normal cells.18, 19, 20 NIS gene transfer into cancer cells causes therapeutic radionuclides (131I, 188Re) to concentrate in these cells, and thus facilitating the use of therapeutic radionuclides to induce cancer cell apoptosis. Our group has previously reported that NIS expressing human hepatocellular carcinoma can be selectively killed given 131I and 188Re accumulation via NIS gene expression,17 and demonstrated that therapy and imaging based on NIS gene transfer could be used to treat anaplastic thyroid carcinomas.38
It has also been shown that the human MUC1 mucin is over-expressed in an incompletely glycosylated form in various human cancers,39, 40 and because high expression of tumor associated antigen hMUC1 is related with rapid tumor progression and a poor prognosis in several types of human cancer, it is considered an attractive immunotherapeutic target. Moreover, cancer DNA vaccine encoding hMUC1 has been studied for the targeting of epithelial cancers expressing high levels of MUC1, and it has been shown that MUC1 DNA vaccination can inhibit MUC1 expressing tumor growth in a preclinical model.41, 42, 43, 44
In the present study, we developed a combination therapy based on an MUC1 vaccine and radionuclide gene therapy. To do this we established an adenocarcinoma colon cancer cell line stably expressing hMUC1, firefly luciferase and sodium iodide symporter by retro- or lentivirus infection, which we refer to as the CMNF cell line. Because CMNF cells express immunogenic target and therapeutic genes, we were able to perform combined cancer DNA immunotherapy and radionuclide gene therapy in living mice. In addition, bioluminescent signals emitted by CMNF allow the monitoring of therapeutic effects.
This combination therapy was found to have the desired effects in vitro and in vivo, and the survival of NIS expressing CMNF cells was effectively reduced to (14.6 ± 1.5)% of the control after 131I treatment. In addition, we observed effective in vivo tumor growth inhibition in the combination therapy group (the pcDNA3-hMUC1 + 131I treatment group) but not in mono therapy group (pcDNA3.1, pcDNA3.1+131I, pcDNA3-hMUC1+PBS treatment group). Tumor growth inhibition occurred in mice immunized with pcDNA3-hMUC1 but not in mice immunized with pcDNA3.1 at 28 days post-CMNF challenge based on caliper and bioluminescent imaging findings (Fig. 4b). However, tumor growth inhibition was not sustained in pcDNA3-hMUC1 + PBS treatment group from 28 days postchallenge.
Although we did not investigate immunologic aspects, we believe that this phenomenon (reduction in tumor growth inhibition) may have been due to an immunogenic effect of the DNA vaccine, the hindrance regulator T-cells, and disruption of cytokine balance in the host.8, 9, 10, 11 Furthermore, we could suggest following 2 reasons for the possible mechanisms of more significant tumor growth inhibition effect after I-131 treatment in MUC1 vaccinated group than other groups. The one is the immune booster response to the MUC1 antigen, which was released from the destroyed CMNF cells through the therapeutic effects by I-131 therapy. As a similar feature, T cell populations are significantly increased after radioiodine therapy in patients with Graves' disease.45 The other mechanism, which might be involved, is that the released hNIS itself from dead cells after radionuclide treatment could also raise immune response against viable CNMF cells with hNIS expression. We recently reported that hNIS vaccination with MIDGE plasmid vector could raise hNIS-associated cell mediated immune responses in mice tumor model.46
This study has a limitation that should be mentioned. We injected MUC1 vaccine before tumor inoculation, which is not accord with the normal situation in cancer patients, but which is consistent with cancer vaccine treatment in a postoperative setting after tumor resection. Thus, it would be more accurate to say that the described combination therapy helps prevent tumor recurrence. In terms of future studies, the repertoire of immune responses initiated by radioiodine gene therapy in living subjects requires investigation. Moreover, because recent sodium iodide symporter radioiodine gene therapies have concentrated on the adenoviral system, which is controlled by specific-promoter regulation, further efforts are required to broaden the scope of the radioiodine/immunotherapy concept.
We demonstrate for the first time that limited tumor growth inhibition achieved using a hMUC1 DNA vaccine can be augmented by radioiodine gene therapy based on sodium iodide symporter over an extended period (52 days) in a preclinical model. We hope that this combination therapy will find a place as a treatment for preventing the occurrence or recurrence of cancer.
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subset: commoncrawl


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text:
John R. Hall, a respected programmer, writer and Linux advocate, passed away on
September 17 at age 24.
John studied computer science at the Georgia Institute of Technology and
was the author of
Linux Games, which he wrote at age 19 while interning
with Loki Software. He later worked at Treyarch. His other interests
included flying, gaming and music.
John chronicled his battle with cancer on his blog,
He and friends also formed an American Cancer Society Relay for Life
team, Team
Melanoma. John's Web page is available
Bayesian filtering for
Bayesian filtering for MoveableType? I didn't even know such a thing existed! I found a plugin written by James Seng.
Mi mas sentido pesame
Lamento mucho la perdida de una persona tan joven, buena y talentosa. Mis condolencias para su familia. Su vida y obra quedan con nosotros.
Muchas personas de la comunidad Linux conocieron su valioso trabajo y estoy seguro sienten mucho pesar por su muerte. Que Dios le de fuerzas y consuelo a su querida familia.
Lamento mucho la perdida de
Lamento mucho la perdida de una persona tan joven, buena y talentosa. Mis condolencias para su familia. Su vida y obra quedan con nosotros.
Rest in Peace
I agree, I'm reading his book now. I hope there will be more people like him willing to share their knowledge. I didn't realize he was so young. I learned so much from the book that I thought I'd search to see if he'd written anything else only to find this page. It's really too bad that such a telented guy died so young.
His blog is really touching.
His blog is really touching. Quite, frankly when I read 'In Memoriam' in my RSS Feed I was expecting some legendary old guy with a thick white beard. Never even dreamt it would be someone as young as 24.
Really unfortunate.
It's sad that he died, but he wasn't exactly well-known. How does he deserve a mention here?
you're an idiot.
you're an idiot.
On the contrary, I think he w
On the contrary, I think he was indeed well known in the Linux community.
Czemu nie!
He was awesomes, and that's as good a reason as any.
I didn't really know him though... I just talked to him in a chatroom briefly several years ago, and I bought his book back when I was into gaming stuff.
You'd probably have to be more into gaming stuff to know of him though, and Linux gaming didn't quite catch on, except in specialty context. (Like cell phone games, and I ~think~ I heard the PS3 uses Linux but I wasn't paying much attention.)
If you weren't into Linux in the late 90s and early 00s, you probably missed all the Loki games and stuff.
Well loved in the community
John was a well known author, contributor, and friend to many of those in the Linux community (me included). RIP
whoever "you" are
just the anonymous community, I guess.
Still can't say he was well-known, but RIP anyway, Mr. Hall.
Come on...
Please man, show some respect. I didn't know him, but he DID exist, and he was important to many people.
To everyone else, I'm sure people like John -shooting stars like him- who light up the sky of understanding, don't disappear. I'm convinced his influence will assist others in their efforts to discover, to create.
My best feelings to his friends and family.
I wish you were still with us
Thanks for sharring your
Thanks for sharring your knowladge with so many people. RIP
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text:
How bit incomes can smooth the rough patches of living
Very often one stands at the cross roads just after graduating college and finding a new job when the onerous task of tackling the burden of education debt comes to the fore and you feel slightly overwhelmed. But this need not trouble you unduly if you manage to generate income that supplements your salary.
Researching jobs at a rudimentary skill level
Your options
The $5 job that could enliven your spare time
- There are tons of jobs on Fiverr that get you $5 per assignment. You could try your hand at writing and translating posts, video and animation work, marketing online spiels or writing LinkedIn profiles and write ups. The sky is the limit and if you have a skill, this is the site that remunerates you for that skill.
Getting paid to help the householder
- There are umpteen tasks around the home that people wish somebody else could do for them. The TaskRabbit site matches the householder's task requirements with handymen and women who are verified and community vetted, that are placed at their disposal for a fee. So whether it is cleaning the home, fetching groceries or decorating the drawing room, you can opt to be the paid tasker who is hired to do all that and more while the householders busy themselves in what they plan to do.
Getting paid to do online surveys and research work
- Companies, the world over do considerable market research before they conceptualize or launch new products. They do this to get a feel of what customers think about their product. One site is FindFocusGroups which pays focus groups for their output. Another site that pays for surveys is Swagbucks. With CashCrate you will be encouraged to try new products and exchange your feedback, and get paid for it. It's important to understand that this concept works if you are getting paid for what you contribute, and it shouldn't be the other way round.
Getting paid to do searches online
- If you leverage BingRewards and Swagbucks by incorporating them as search engines you automatically get a trickle of side income as you search the web daily for your personal needs.
Booking income by renting spaces to strangers
- If you are not yourself living in rented accommodation or subject to HOA rules, you can rent out a limited space or your entire home while you are travelling or leaving the home unoccupied, and earn some extra money. There are trusted sites like San Francisco based Airbnb, Austin based HomeAway and Home Away spin off VRBO that provide online platforms to list your real estate and to browse the sites for rental property in global destinations.
Let the car help you earn money
- It is possible that your car remains idle over the weekends or during office hours when you use the public transport. You could list your vehicle on RelayRides so that others can commandeer a driver to use it when they need a vehicle. Alternatively, you could sign up with Lyft or Uber and get paid hourly for driving perfect strangers to their destination.
Leverage money to earn more cash
- Many banks announce an attractive sign up bonus on opening a checking account.
- Insisting on paying the balance promptly every month to prevent interest overload and grab cash back offers on purchases made through credit cards.
- Shifting savings to a higher income earning facility or account.
- Leveraging Ebates and Upromise to utilize cash backs for your loans.
Creating cash from disposable items
It's a double whammy – you get to clean your cupboards, rooms, attic and garage and generate fresh money by disposing the things you don't need. Arrange a yard sale or push sales through eBay or Craigslist where the items can fetch more money. The range of outlets available for selling stuff is mind boggling. For books and school texts there is Textbooks, Amazon and Chegg; for old mobiles and electronic gadgets there's Gazelle, and Pre owned Wedding Dresses for disposing a bridesmaid's outfit or wedding dress.
Researching jobs at an intermediate level
Craftwork as a money earning proposition
- If you have an inborn skill or creativity that helps you design or craft handmade items and you are familiar with working on a variety of textures like wood, bamboo, metal, clothing and embroidery, you can make stuff for sale on Etsy.
Blogging as a wish fulfiller and money earner
- You can let your creative writing skills bloom and gain a lot of personal satisfaction and fulfill your desire to communicate in a language people can understand. It also helps make money on the side. Surveys say around 10% of bloggers are earning up to $10,000 per month. Having a degree in Creative writing, English or Journalism would be a bonus.
Leverage a farmer's market to sell organic produce
- It is possible that you have a kitchen garden that grows herbs and veggies organically that could be in great demand in the local farmer's market and fetch a good price for you. Just ensure you are not violating food industry rules and state regulations.
The Pet care industry
- There is a huge industry caring for pets in America, and one of the best ways to contribute your might is to get hired as a pet sitter to do day care or take pets for walks. It helps a great deal if you have a veterinary degree or you are skilled in veterinary medicine. Petsitter, Care and Craigslist will keep you busy on week days and weekends.
The Childcare industry
- Child care opportunities are enormous especially in active communities, and parents always need help with baby sitting and childcare routines. Having majored in child care related subjects is a definitive plus point in getting these paying jobs. Care website hosts data on jobs that are in great demand. Using Nanny in the clouds you can check out parents that list their childcare assistance needs when they board a flight.
Researching jobs at a progressive level
Writing and translation skills that you can exploit to your advantage
- If you are fluent in one or more foreign languages your services as a translator will be much in demand through websites like Upwork, Gengo or Indeed, and you can float a resume on Monster to build your career in what is considered a very lucrative field.
If you have excellent command over English and can post views fluently on wide ranging topics, sites like Upwork and Amazon have tons of work that can earn you decent cash.
Tutoring assignments
- If you are skilled in fitness, sports, cookery, dancing or fashion designing or adept at teaching math or any other college subject, you could teach someone else for a fee. You could just as well coach students to compete in ACT and SAT exams. If your skills are epitomized in a master's degree or any higher technical qualification there may be online faculty posts that could open doors for you. Skillshare is a good site that allows you to teach a variety of courses online for a fee if you sign in as a service provider.
The world is moving online and there are multiple avenues to keep yourself busy while you earn money on the side. Explore the tips we have shared with you and chart a new path into areas you never tried before. Who knows? What starts off as a temporary vocation might just become a lifetime permanent job and money spinner. Car Title Loans Santa Clara 5201 Great America Parkway, Santa Clara, CA 95054 (408) 703-5542


text:
The Guns of Adam Riches, Series 1 Episodes Episode guide
Back up to: The Guns of Adam Riches
The Third Pole
4/4 Martin started out as a software developer, but ended up as a legendary explorer.
The Ballad of Big Rich
3/4 Adam Riches takes the listener back to the Wild West to tell the story of Big Rich.
2/4 Timecops visit the BBC to try and prevent Adam from making an offensive radio programme.


text:
Page 1
RESEARCH ARTICLEOpen Access
Ethnicity and elevated liver transaminases among
newly diagnosed children with type 2 diabetes
Omar D Hudson1, Martha Nunez3and Gabriel Q Shaibi1,2,3*
Background: To examine the influence of ethnicity on liver transaminases among adolescents with type 2 diabetes
mellitus (T2DM).
Methods: A retrospective medical chart review of 57 (30 males and 27 females) newly diagnosed patients with
T2DM. Ethnicity was determined by self-report and height, weight, body mass index (BMI) and glycosylated
hemoglobin (HbA1c) were obtained using standard clinical procedures. Fasting levels of alanine aminotransaminase
(ALT) and aspartate aminotransferase (AST) were collected prior to the initiation of any therapy.
Results: Age, gender, height, weight, BMI, and HbA1c did not differ between ethnic groups. Compared to African-
Americans, Hispanics had significantly higher ALT (23.9 ± 3.4 vs. 107.8 ± 20.3, p=0.002) and AST (17.7 ± 2.5 vs. 71.1 ±
15.7, p<0.001) and were significantly more likely to have ALT values above the upper limit of normal (20% vs. 71%,
p=0.005) and twice the upper limit of normal (0% vs. 39%, p=0.05) as well as AST values above the upper limit of
normal (0% vs. 53%, p=0.002). No differences in ALT or AST were found between Hispanics and non-Hispanic whites or
between African-Americans and non-Hispanic whites.
Conclusions: These preliminary findings suggest that Hispanic children with T2DM may be at higher risk for
developing non-alcoholic fatty liver disease and indicate that a comprehensive hepatic evaluation is warranted in this
population. Future studies that incorporate more precise and proximal measures of liver health are warranted in this
Keywords: Type 2 diabetes mellitus, Fatty liver, Alanine aminotransferase, Aspartate aminotransferase
Childhood obesity is increasing worldwide and nearly
35% of children and adolescents in the United States are
overweight or obese [1]. Coinciding with this epidemic is
an increase in obesity-related metabolic comorbidities
such as type 2 diabetes mellitus (T2DM) and non-
alcoholic fatty liver disease (NAFLD) [2,3]. These
chronic conditions present challenges to pediatric practi-
tioners as no consensus on their management exists and
there is limited evidence regarding long-term prognosis.
Both conditions appear to be related to the underlying
pathophysiologic process of insulin resistance [4,5] and
may act synergistically to place youth at increased risk
for premature morbidity and mortality. Only 1 study to
date has examined NAFLD risk in youth with T2DM
and found that as many as 48% of those diagnosed with
T2DM also exhibit elevated liver transaminases [6]. The
authors concluded that the high prevalence of elevated
serum aminotransferases among children with T2DM
may be an indication of concomitant NAFLD in this
Although pediatric obesity has increased worldwide,
certain ethnic subgroups of youth are disproportionately
impacted by both NAFLD and T2DM. In particular,
Hispanic and African-American adolescents are more
likely to present with T2DM compared to non-Hispanic
whites but Hispanic adolescents are thought to be at
highest risk for NAFLD while African-Americans are at
lowest risk [7]. To date, no studies have examined the
degree to which liver transaminases are differentially ele-
vated across ethnic groups among youth diagnosed with
* Correspondence: firstname.lastname@example.com
1Division of Pediatric Endocrinology and Diabetes, Phoenix Children's
Hospital, Phoenix, AZ, USA
2Center for Metabolic and Vascular Biology, Arizona State University,
Full list of author information is available at the end of the article
© 2012 Hudson et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Hudson et al. BMC Pediatrics 2012, 12:174
Page 2
T2DM. Given the disproportionate burden of obesity-
related disease among minority youth, arriving at a bet-
ter understanding of NAFLD risk among youth with
T2DM is an important step for improving care and
management of this vulnerable population. Therefore,
the purpose of this preliminary study was to compare
serum liver transaminase levels as markers of NAFLD
risk in African-American, Hispanic, and non-Hispanic
white youth diagnosed with T2DM and assess whether
the degree to which these markers are elevated differs by
The medical charts of patients seen with T2DM in the
Division of Pediatric Endocrinology at Phoenix Chil-
dren's Hospital between 2005 and 2006 were reviewed.
The diagnosis of T2DM was based on the American
Diabetes Association criteria in those with negative islet
cell, GAD-65 and insulin antibodies [8]. Those diag-
nosed with T2DM based on known secondary complica-
tions of disease or medications (e.g., cystic fibrosis,
organ transplant anti-rejection treatment, chemother-
apy) or presumed liver disease secondary to viral ill-
nesses, genetic diseases of the hepatobiliary system or
autoimmune diseases were excluded. Also excluded were
patients in whom the method of diagnosis was not clear
or those with insufficient metabolic or ethnicity data
available. The Scientific Review Committee and Institu-
tional Review Boards of Phoenix Children's Hospital
approved this study.
Data collection
The following was extracted from the medical charts:
age, gender, ethnicity, height, weight, BMI, HbA1C, and
fasting liver transaminases (ALT and AST). All labora-
tory values were determined at the time of diagnosis
prior to the initiation of therapy.
Data analysis
Data are reported as percentages for categorical variables
(gender, ethnicity) or means ± standard error for con-
tinuous variables (age, height, weight, body mass index
(BMI), ALT, AST, and HbA1c). General linear modeling
was used to compare metabolic variables between ethnic
groups with Bonferroni adjustments for multiple com-
parisons. Transaminases were log transformed for
normalization however un-transformed values are pre-
sented for ease of interpretation. Chi-Squared analyses
with Fisher exact test were performed to examine
whether the incidence of transaminases above the upper
limit of normal (ULN) (ALT ≥ 35 IU/L, AST ≥ 41 IU/L),
twice the ULN (ALT ≥ 70 IU/L, AST ≥ 82 IU/L) and
three times the ULN (ALT ≥ 105 IU/L, AST ≥ 123 IU/L)
differed by ethnicity based on normal values provided by
the clinical lab (Quest Diagnostics Inc, Nichols Institute,
San Clemente, CA). Statistical significance was deter-
mined based on a P value of < 0.05. SPSS statistics 18.0
was used to analyze the data (SPSS Inc, Chicago, IL).
Fifty-seven patients had pertinent metabolic and ethni-
city data available and were included in the present ana-
lysis. Descriptive characteristics are presented in Table 1.
Thirty-eight patients (66%) were identified as Hispanic,
10 (17%) were African-American and 9 (16%) were non-
Hispanic white. No significant ethnic differences were
noted in age, gender, height, weight, BMI, or HbA1C.
Liver transaminase data
ALT and AST data are presented in Figure 1. Both ALT
and AST differed by ethnicity (R2= 0.20, F = 6.768, p =
0.002 for ALT and R2= 0.24, F = 8.804, p < 0.001 for
AST) with pair-wise comparisons showing Hispanic
youth with significantly higher ALT (p = 0.002) and AST
(P < 0.001) levels compared to African-Americans. No
significant differences were noted between Hispanics
and non-Hispanic whites for either ALT (p=1.0) or AST
(p=0.36). Similarly, no significant differences were noted
between non-Hispanic whites and African-Americans
for either ALT (p=0.09) or AST (p=0.18). Ethnicity
remained a significant predictor of both ALT and AST
after including BMI and HbA1c in the models (F=3.487,
p=0.04 and F=3.557, p=0.04, respectively).
Table 1 Descriptive characteristics by ethnicity
HispanicAfrican-AmericanNon-Hispanic White
Age at Diagnosis (yrs)13.1 ± 0.313.8 ± 0.613.5 ± 01.1
Gender (M/F)23/151/96/3
Height (cm)161.7 ± 2.4160.7 ± 3.8162.5 ± 5.7
Weight (kg)
BMI (kg/m2)
90.9 ± 11.092.6 ± 9.495.7 ± 11.0
35.0 ± 1.138.9 ± 3.335.5 ± 3.5
HbA1C (%)8.9 ± 0.99.6 ± 0.48.0 ± 0.9
Data expressed as means ± SEM. Abbreviations: BMI (body mass index).
Hudson et al. BMC Pediatrics 2012, 12:174
Page 2 of 6
Page 3
The prevalence of elevated transaminases above the
ULN, twice the ULN and three times the ULN by ethnicity
are presented in Table 2. Hispanics were significantly more
likely to have ALT levels above the ULN and twice the
ULN (p = 0.008 and 0.05, respectively) with a trend towards
significance for having ALT levels 3 times the ULN (p =
0.08) compared to African-Americans or non-Hispanic
whites. Additionally, Hispanics were more likely to have
AST levels above the ULN (p = 0.003) compared to other
With the increased prevalence of childhood obesity noted
in recent decades, NALFD has become the most common
liver abnormality found among the pediatric population
[3]. Moreover, NAFLD risk is disproportionately higher
among Hispanic youth where elevated ALT levels have
been reported in more than 11% of Hispanic adolescents
in the US [9], almost 24% of overweight Hispanic youth
[10], and as many as 60% of obese Hispanic youth in a
clinical sample [11]. The current report extends the avail-
able science regarding NAFLD-related health disparities
to newly diagnosed adolescents with T2DM and suggest
that more than 70% of Hispanic youth with T2DM exhibit
elevated ALT levels. These data support recent findings
that youth with T2DM are at considerable risk for prema-
ture morbidity and mortality [12].
NAFLD and T2DM are thought to share a common
pathophysiology related to insulin resistance [13]. Obese
youth with NAFLD are significantly more insulin resist-
ant than obese youth who do not exhibit NAFLD [14].
Similarly, adolescents with T2DM are significantly more
Hispanics American-AmericansWhites
ALT and Ethnicity
p = 0.002N.S.
Hispanics American-Americans Whites
AST and Ethnicity
p < 0.001 N.S.
Figure 1 AB, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values in newly diagnosed youth with type 2
diabetes mellitus (T2DM). Data are presented as means ± SE.
Table 2 Percentage of patients with elevated liver transaminases by ethnicity
Hispanic (%) African-American (%) Non-Hispanic White (%) P-value
ALT - Normal298012
Above the ULN7120 88 0.008
Twice the ULN 39022 0.05
Three times the ULN 290 11 0.09
AST - Normal47 100 89
Above the ULN530 11 0.003
Twice the ULN2100 0.17
Three times the ULN800 0.45
ALT: Alanine aminotransferase, AST: aspartate aminotransferase, ULN: Upper Limit of Normal.
Hudson et al. BMC Pediatrics 2012, 12:174
Page 3 of 6
Page 4
insulin resistant than BMI-matched adolescents with
normal glucose tolerance [4]. Although obesity and insu-
lin resistance are common characteristics of youth with
both NAFLD and T2DM, these traits alone do not ex-
plain why Hispanic patients in our study exhibited
higher transaminase values. Our patients exhibited simi-
lar descriptive and glycemic profiles in terms of obesity
and severity of diabetes (i.e. similar BMI and HbA1c)
which, suggests that ethnicity may further play a role
in the pathogenesis of NAFLD in the obese diabetic
population. Goran and colleagues [15] have reported
that Hispanic and African-American youth are significantly
more insulin resistant compared to non-Hispanic whites.
Interestingly, the authors noted that the associated
compensatory response to insulin resistance is different
between these minority groups and may indicate ethnic-
specific mechanisms underlying obesity-related diseases.
Unfortunately, glucose and insulin levels were not available
in our sample, limiting our ability to examine whether
variations in insulin resistance may contribute to the
observed differences in elevated transaminases between
groups. A study by Schwimmer et al [16] identified an
extremely high heritability estimate (h2= 0.850; standard
error, 0.325), for fatty liver disease in a predominantly
Hispanic cohort suggesting that Hispanics may be pre-
disposed to developing NAFLD. This same group
hypothesized that African-Americans may either have a
protective factor or lack a vulnerability factor for the de-
velopment of fatty liver [17]. Collectively, these findings
suggest that genetic factors may contribute to the higher
risk of NAFLD among Hispanic youth. In particular,
when coupled with obesity, severe insulin resistance, and
T2DM, Hispanic youth may be at extreme risk for pre-
mature hepatic morbidity.
The retrospective nature of this report precludes
causal conclusions regarding ethnic-specific disease
mechanisms or trajectories. A recent study in a
community-sample of Korean adults suggests that eleva-
tions in ALT predict the development of T2DM over
time [18]. A study in obese youth from the United King-
dom suggests that youth with the metabolic syndrome
and those with a family history of T2DM, both of which
are risk factors for developing T2DM, are more likely to
exhibit elevated ALT levels [19]. Therefore, a prospective
study following normoglycemic youth as well as patients
with T2DM over time or through a course of treatment
may better identify potential causal relationships between
hepatic health and T2DM or whether gene-environment
interactions concomitantly impact the development
NAFLD and T2DM. Although our sample had fewer
African-Americans and non-Hispanic whites compared
to Hispanics this is most likely a function of the ethnic
disparities in T2DM risk coupled with the demographics
of the local Phoenix metropolitan area. Most of the
patients resided in Maricopa County Arizona where
Phoenix Children's Hospital is the only tertiary care
referral center for Pediatrics. The most recent census
data (2010) showed Hispanics comprise 40.8% of the
population while African-Americans comprised 6.5%.
These data coupled with the demographics of the pa-
tient population in our study support disparities in
T2DM risk in the local community and may partially
explainthe limitednumber
compared to Hispanics and non-Hispanic whites. We
acknowledge the limited sample size of the entire co-
hort and especially the non-Hispanic groups. To our
knowledge, the only other publication to date examin-
ing liver enzymes in youth with T2DM described 48
youth from Colorado in whom 65% (n=31) had liver
enzymes measured at diagnosis [6]. By comparison, the
multi-center SEARCH for Diabetes in Youth Study
representing 6-centers from four geographically defined
populations of 3.5 million youth identified a total of
446 African-American,Hispanic,
White youth with T2DM in their initial year [20].
Given the paucity of published data in youth with
T2DM and the fact that our report is the first to de-
scribe the impact of ethnicity on NAFLD in youth with
T2DM we expect that future studies will build upon
these findings using more representative samples.
It is noteworthy that elevated liver transaminases only
appear to be indicators of liver inflammation and are not
diagnostic of NAFLD [7]. However, in follow-up of six
Hispanic patients with ALT or AST more than twice the
ULN who underwent liver ultrasound, characteristics
consistent with fatty liver disease were found in all six.
Additionally, two of these patients had splenomegaly on
the ultrasound with follow up biopsy confirming fibrosis
(Grade III in a 15 y/o Hispanic male and Grade II in a
16 year old Hispanic female). The remaining four were
followed by both the endocrinology and gastroenterology
services. Future studies should employ more sophisti-
cated imaging methods such as magnetic resonance
spectroscopy to better quantify liver fat and NAFLD in
youth with T2DM [21]. Not only will these studies pro-
vide more definitive information on ethnic differences in
NAFLD risk, but may also be useful in developing clin-
ical prediction models for when and who to refer for
consult with a hepatologist.
As the prevalence of obesity increases in the pediatric
population it could be argued that all high-risk patients
including Hispanics and especially those newly diag-
nosed with T2DM have liver transaminases evaluated. In
support of this argument, the American Medical Associ-
ation recently released expert committee recommendations
regarding pediatric obesity which suggested biannual
screening for NAFLD by transaminase evaluation start-
ing at 10 years of age for children with a BMI ≥95th
of African-Americans
and non-Hispanic
Hudson et al. BMC Pediatrics 2012, 12:174
Page 4 of 6
Page 5
percentile and those with a BMI between the 85th to
94th percentile who have other risk factors [22]. Further-
more, the committee suggested that ALT or AST results
2 times normal levels should prompt consultation with a
pediatric hepatologist. The importance of regular trans-
aminase evaluation is critical as hepatic inflammation
can quickly progress to frank fibrosis. In a review of chil-
dren diagnosed with NALFD in Toronto, Rashid et al
[23]. showed a high prevalence (77%) of progression to
liver inflammation and fibrosis. This rapid trajectory
underscores the importance of follow-up in those chil-
dren with elevated liver transaminases as end-stage com-
plications can be present in childhood. Particularly
concerning is the process starting at a young age even if
advanced findings are not yet present. Continued and
improved interaction between gastroenterologists and
pediatric endocrinologists are needed as the team ap-
proach to medical management of patients with T2DM
may require more comprehensive medical evaluation in-
cluding liver biopsies. At our institution, biopsies are typ-
ically performed only if the ultrasound suggests cirrhosis.
Further longitudinal studies may provide better guide-
lines regarding the progression of liver disease in relation
to the timing of biopsy. Our data also suggest that varia-
tions in the management should occur based on ethnici-
ties possibly using different timing of monitoring and
goals of treatment. One might more readily refer and/or
follow more closely a Hispanic patient with laboratory or
imaging studies suggesting NAFLD.
Our preliminary findings suggest that Hispanic youth
with T2DM are more likely to have abnormal liver trans-
aminases, which, in turn, could indicate in a greater risk
for developing NAFLD compared to their African-
American and non-Hispanic white peers. Although these
findings need to be confirmed via prospective studies
using more accurate assessments of hepatic health, the
increasing rates of NAFLD and T2DM renders our re-
port important to clinicians and researchers working
with obese youth.
T2DM: Type 2 diabetes mellitus; ALT: Alanine aminotransferase;
AST: Aspartate aminotransferase; NAFLD: Non-alcoholic fatty liver disease;
BMI: Body Mass Index; ULN: Upper Limit of Normal.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
OH conceptualized the study, extracted the data, and drafted the
manuscript. MN extracted the data and edited the manuscript. GQS
conceptualized the study, analyzed the data, and edited the manuscript. All
authors read and approved the final manuscript.
The authors would like that thank Drs. Mitchell Shub and Tamir Miloh from
the Division of Pediatric Gastroenterology at Phoenix Children's Hospital for
their thoughtful insights during the development of this manuscript.
Author details
1Division of Pediatric Endocrinology and Diabetes, Phoenix Children's
Hospital, Phoenix, AZ, USA.2Center for Metabolic and Vascular Biology,
Arizona State University, .3College of Nursing and Health Innovation, Arizona
State University, 500 N. 3rd St., Phoenix, AZ 85004, USA.
Received: 28 June 2012 Accepted: 25 October 2012
Published: 7 November 2012
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Body Mass Index in US Children and Adolescents, 2007–2008. JAMA
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Diabetes in Youth in the United States. JAMA 2007, 297(24):2716–2724.
3. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C:
Prevalence of Fatty Liver in Children and Adolescents. Pediatrics 2006,
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Page 5 of 6


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Home > News > WFU lands investors for two nano spinoffs
July 20th, 2007
WFU lands investors for two nano spinoffs
An investment group involved in the creation of nearly a dozen nanotechnology companies over the past three years has licensed technology from Wake Forest University.
The group is planning to manage the spinoffs of two new companies looking to revolutionize the way energy is generated and put to use.
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President Obama will use his State of the Union Address on Tuesday to outline "concrete, real, practical proposals" — even if Congress isn't on board with each of them.
Dan Pfeiffer said Mr. Obama's go-it-alone message isn't meant to be confrontational and that the president is willing to find common ground with Republicans, where possible.
In two days, Mr. Obama will address Congress with his popularity numbers in negative territory.
He is trying to rejuvenate his second term after a dismal 2013 in which Congress beat back his gun-control proposals, House Republicans allowed his immigration reforms to stall and his signature health law faced near-disaster upon its October rollout.
"We need to show the American people that we can get something done, either with Congress or on our own," Mr. Pfeiffer told CNN's State of the Union with Candy Crowley.
Republicans are unlikely to be impressed by the White House's rhetoric.
"It sounds vaguely like a threat, and it has a certain amount of arrogance," Sen. Rand Paul, Kentucky Republican, told CNN.
He said the federal government relies on a balance of powers, and that the president should realize that legislating is tough business. "It takes consensus," he said.


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Are you Feng Qiu?Claim your profile
Publications (125)264.94 Total impact
Article: Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cellsInternational Journal of Oncology 09/2015; DOI:10.3892/ijo.2015.3186 · 3.03 Impact Factor
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ABSTRACT: An exploration for Nitric Oxide (NO) inhibitors from the rhizomes of Curcuma phaeocaulis afforded one new salvialane-type sesquiterpene, phasalvione (1), two novel nor-sesquiterpenes, phaeocaudione (2) and phaeocauone (3), one aromatic acid 3-methyl-4-(3-oxo-butyl)-benzoic acid (4), two γ-elemene-type sesquiterpenes, 8β(H)-elema-1,3,7(11)-trien-8,12-lactam (5) and (5R, 8R, 10R)-8-methoxy-elema-1,3,7(11)-trien-8,12-lactone (6), one eudesmane-type sesquiterpene, phaeusmane I (7), and one cyclic diarylheptanoid, phaeoheptanoxide (8). Their structures were established based on extensive spectroscopic analysis. The absolute configurations of compounds 1 and 2 were assigned using the circular dichroism data of the [Rh2(OCOCF3)4] complex, and the absolute configuration of 1 was further established by single crystal X-ray crystallography, whereas that of 6 was deduced by circular dichroism (CD) method. Furthermore, inhibitory effects of the isolated compounds on nitric oxide production in LPS-activated macrophages were evaluated. Compounds 1, 3 and 4 showed strong inhibitory activities on NO production with IC50 values of 7.46±0.69, 2.35±0.17 and 3.49±0.31 μM, respectively. A plausible biosynthetic pathway for 1-4 in C. phaeocaulis was also discussed.Organic & Biomolecular Chemistry 06/2015; 13(30). DOI:10.1039/C5OB00964B · 3.56 Impact Factor
Article: Four new sesquiterpenes from the rhizomes of Curcuma phaeocaulis and their iNOS inhibitory activities[Show abstract] [Hide abstract]
ABSTRACT: Three new guaiane-type sesquiterpenes named phaeocaulisins K-M (1-3), and one germacrane-type sesquiterpenoid with new ring system of 1,5- and 1,8-ether groups named phagermadiol (4), were isolated from rhizomes of Curcuma phaeocaulis. Their structures were established based on extensive spectroscopic analysis. Compound 1, the first example of norsesquiterpene with tropone backbone, and compound 3 with a novel 1,2-dioxolane sesquiterpene alcohol were isolated from the genus Curcuma. All of the isolated compounds were tested for inhibitory activity against lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compound 3 inhibited NO production with IC50 value of 6.05 ± 0.43 μM. The plausible biosynthetic pathway for compounds 3 and 4 in C. phaeocaulis was also discussed.Journal of Asian natural products research 06/2015; 17(5):1-9. DOI:10.1080/10286020.2015.1046449 · 0.91 Impact Factor
Dataset: Oridonin induces G2M arrest and apoptosis via activating ERK-p53 apoptotic pathway and inhibiting PTK-Ras-Raf-JNK survival pathway in murine fibrosarcoma L929 cells.
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ABSTRACT: Glycyrrhizin (GZ), the main active component of licorice, is a widely used therapeutic in the clinic. Depending on the disease, the treatment may involve a long course of high dose GZ. Another component of licorice, glycyrrhetinic acid (GA), is the main active metabolite of GZ and is thought to be responsible for the majority of the pharmacological properties of GZ. Therefore, GZ and GA are both used for therapeutic purposes. In addition, GZ and GA are also widely used to sweeten and flavor foods. Due to this widespread, multifaceted use of these substances, potential drug interactions with GZ and GA have recently gained attention. Along these lines, this review covers the known effects of GZ and GA on drug-metabolizing enzymes and efflux transporters. We conclude that both GZ and GA may have an effect on the activity of CYPs. For example, GZ may induce CYP3A activity through activation of PXR. Also, GZ and GA may affect glucuronidation in rats and humans. Furthermore, 18β-GA is a potent inhibitor of P-gp, while GZ and GA are inhibitors of MRP1, MRP2 and BCRP. The pharmacokinetics and pharmacodynamics of many medications may be altered when used concurrently with GZ or GA, which is also covered in this review. Overall, GZ, GA or related products should be taken with caution when taken with additional medications due to the possible drug interactions.Drug Metabolism Reviews 03/2015; 47(2):1-10. DOI:10.3109/03602532.2015.1029634 · 5.36 Impact Factor
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ABSTRACT: Biocatalysis of curcumenol (1) was performed by Mucor polymorphosporus AS 3.3443. Six metabolites including five new compounds were obtained, and their structures were elucidated as 10β-hydroxy-9,10-dihydrocurcumenol (2), 2β-hydroxycurcumenol (3), 15-hydroxycurcumenol (4), 12-hydroxycurcumenol (5), 1-hydroxy-4αH-guai-1,6,9-triene-2,8-dione (6), and 5-hydroxycarbonyl-1-oxo-3,7-dimethylindane (7) by spectroscopic analysis. M. polymorphosporus catalyzed unusual degradation and rearrangement reactions to generate a ring-contracted metabolite (7) of curcumenol (1). Curcumenol (1) and metabolites 4-7 exhibited inhibitory activities against lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, with 7 exhibiting more potent activity than curcumenol.Journal of Natural Products 03/2015; 78(4). DOI:10.1021/np500845z · 3.80 Impact Factor
Article: Sesquiterpenes from the essential oil of Curcuma wenyujin and their inhibitory effects on nitric oxide production[Show abstract] [Hide abstract]
ABSTRACT: Three new sesquiterpenes including a new elemane-type sesquiterpene, 5βH-elem-1,3,7,8-tetraen-8,12-olide (1), and two new carabrane-type sesquiterpenes, 7α,11-epoxy-6α-methoxy-carabrane-4,8-dione (2) and 8,11-epidioxy-8-hydroxy-4-oxo-6-carabren (3), together with eight known sesquiterpenes (4-11) were isolated from Curcuma wenyujin Y. H. Chen et C. Ling. Their structures were elucidated based on extensive spectroscopic analyses. A possible biogenetic scheme for the related compounds was postulated. All of the isolated compounds were tested for inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages. Meanwhile, preliminary structure-activity relationships for these compounds are discussed. Copyright © 2015. Published by Elsevier B.V.Fitoterapia 03/2015; 103. DOI:10.1016/j.fitote.2015.03.021 · 2.35 Impact Factor
Article: Cadinane sesquiterpenes from Curcuma phaeocaulis with their inhibitory activities on nitric oxide production in RAW 264.7 cells[Show abstract] [Hide abstract]
ABSTRACT: Four new cadinane-type sesquiterpenes named phacadinanes A-D (1-4) were isolated from the rhizomes of Curcuma phaeocaulis. Their structures were elucidated by 1D and 2D NMR, as well as accurate mass measurements. Compound 4 was the first example of a rare 4,5-seco-cadinane sesquiterpene isolated from the Zingiberaceae family. Furthermore, inhibitory effects of the isolated compounds on nitric oxide production in LPS-activated macrophages were evaluated. Compounds 1 and 2 showed strong inhibitory activities on NO production with IC50 values of 3.88±0.58 and 2.25±0.71 μM, respectively. A possible biogenetic pathway for 4,5-seco-cadinane sesquiterpene (4) was postulated. Copyright © 2015. Published by Elsevier B.V.Fitoterapia 03/2015; 103. DOI:10.1016/j.fitote.2015.03.020 · 2.35 Impact Factor
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ABSTRACT: Biotransformations of curcumenol (1) were performed by four fungal strains, Mucor spinosus AS 3.2450, Penicillium urticae IFFI 04015, Cunninghamella echinulata AS 3.3400, Aspergillus carbonarius IFFI 02087. Five metabolites were prepared in the biotransformation process of 1, and their structures were elucidated as 15-hydroxycurcumenol (2), 1α-hydroxycurcumenol (3), 14-hydroxycurcumenol (4), 3β-hydroxycurcumenol (5) and 12-hydroxycurcumenol (6) by spectroscopic data analysis. Among them, metabolites 2-5 are novel. All of these four fungal strains showed the ability of highly stereo- and regiospecific hydroxylation for the substrate (1), which could be used as tools for preparing the hydroxylated derivatives and in vivo metabolites of curcumenol. In addition, the inhibitory effects of substrate and obtained products on nitric oxide production in lipopolysaccaride-activated macrophages were evaluated. The substrate (1) and metabolites 2, 5, and 6 showed significant inhibitory effects.Journal of Molecular Catalysis B Enzymatic 01/2015; 115. DOI:10.1016/j.molcatb.2015.01.005 · 2.13 Impact Factor
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ABSTRACT: Three new lanostane-type triterpenes, inonotusanes A-C (1-3), and a new naturally occurring one, 3β-hydroxy-25,26,27-trinorlanosta-8,22E-dien-24-oic acid (4), together with sixteen known triterpenoids (5-20), including 13 lanostane derivatives, 2 lupanes and 1 oleanane-type triterpene were isolated from the sclerotia of Inonotus obliquus. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRMS. Compounds 6, 8, 18 and 20 exhibited strong cytotoxicity against A549 tumor cell lines, with IC50 values of 2.34, 1.63, 8.39 and 5.39μM, respectively. Seven compounds (3, 9, 10, 12, 18-20) exhibited moderate cytotoxicity against A549, HT29, Hela or L1210 tumor cell lines. Copyright © 2014. Published by Elsevier B.V.Fitoterapia 12/2014; 101. DOI:10.1016/j.fitote.2014.12.005 · 2.35 Impact Factor
Article: Curcumin and its major metabolites inhibit the inflammatory response induced by lipopolysaccharide: Translocation of nuclear factor-κB as potential target[Show abstract] [Hide abstract]
ABSTRACT: The aim of the present study was to investigate and compare the anti‑inflammatory activities of curcumin and its three metabolites, tetrahydrocurcumin, hexahydrocurcumin and octahydrocurcumin in lipopolysaccharide (LPS)‑stimulated RAW 264.7 macrophage cells. The results demonstrated that overproduction of nitric oxide (NO) was potently inhibited following treatment with curcumin and its three metabolites. In addition, curcumin and tetrahydrocurcumin significantly inhibited the release of prominent cytokines, including tumor necrosis factor‑α (TNF‑α) and interleukin‑6 (IL‑6); however, hexahydrocurcumin and octahydrocurcumin did not significantly alter cytokine release. Furthermore, the present study investigated the effect of curcumin and its metabolites on the expression of inducible NO synthase (iNOS), cyclooxygenase‑2 (COX‑2) and activated‑nuclear factor kappa B (NF‑κB); the results showed that curcumin and its three metabolites significantly inhibited LPS‑mediated upregulation of iNOS and COX‑2 as well as NF‑κB activation. However, curcumin exerted a more potent effect on LPS‑stimulated RAW 264.7 cells compared to that of its three metabolites, of which tetrahydrocurcuim was found to be the most pharmacologically active. In conclusion, the results of the present study demonstrated that curcumin and its major metabolites inhibited the LPS‑induced inflammatory response via the mechanism of inhibiting NF‑κB translocation to the nucleus.Molecular Medicine Reports 12/2014; 11(4). DOI:10.3892/mmr.2014.3079 · 1.55 Impact Factor
Article: Upregulated expression level of the growth factor, progranulin, is associated with the development of primary Sjögren's syndrome[Show abstract] [Hide abstract]
ABSTRACT: The aim of the present study was to investigate the expression and effect of progranulin (PGRN) in patients with primary Sjögren's syndrome (pSS). In total, 26 newly diagnosed pSS patients and 26 healthy subjects were enrolled in this study. The serum levels of PGRN and the inflammatory factor, interleukin-6 (IL-6), were detected using ELISA. In addition, the mRNA expression levels of these molecules were detected by quantitative polymerase chain reaction. The serum levels of PGRN and IL-6 in the pSS patients increased significantly compared with the healthy controls (P<0.05). During the remission stages, the levels of PGRN and IL-6 were comparable to those of the healthy controls. The serum level of PGRN in the pSS patients was shown to correlate with that of IL-6 in the pre-treatment and post-treatment stages. PGRN was upregulated in the pSS patients, indicating a possible role of PGRN in the pathogenesis and development of pSS.Experimental and therapeutic medicine 11/2014; 8(5):1643-1647. DOI:10.3892/etm.2014.1981 · 1.27 Impact Factor
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ABSTRACT: Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saporiin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3 beta,28-dihydroxy-18 alpha H-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 mu M. (c) 2014 Elsevier B.V. All rights reserved.Biochemical Systematics and Ecology 09/2014; 40:49–52. DOI:10.1016/j.bse.2011.09.010 · 0.97 Impact Factor
Article: Eudesmane-Type Sesquiterpenes from Curcuma phaeocaulis and Their Inhibitory Activities on Nitric Oxide Production in RAW 264.7 Cells[Show abstract] [Hide abstract]
ABSTRACT: Eight eudesmane-type sesquiterpenes – phaeusmanes A–H (1–8) – isolated for the first time in this work, and four others (9–12) isolated for the first time from plants in this work, together with fourteen known eudesmane derivatives, were isolated from the rhizomes of Curcuma phaeocaulis. Their structures were elucidated by 1D and 2D NMR and CD spectroscopy and HRMS. Compound 8 is the first example of a nitrogen-containing eudesmane-type sesquiterpene isolated from the genus Curcuma. Furthermore, inhibitory effects of the isolated compounds on NO production in lipopolysaccharide-activated macrophages were evaluated. Compounds 1, 6, 10, 19, 22, and 24 showed strong inhibitory activities on NO production with IC50 values of 3.2, 4.8, 1.2, 0.8, 3.8, and 0.8 μM, respectively. Preliminary structure–activity relationships for these compounds are proposed. A possible biogenetic pathway for nitrogen-containing eudesmane-type sesquiterpene 8 is postulated.European Journal of Organic Chemistry 09/2014; 2014(25). DOI:10.1002/ejoc.201402465 · 3.07 Impact Factor
Article: Simultaneous determination of three glucuronide conjugates of scutellarein in rat plasma by LC–MS/MS for pharmacokinetic study of breviscapine[Show abstract] [Hide abstract]
ABSTRACT: A selective and sensitive LC–MS/MS method was developed and validated for simultaneous determination of three glucuronide conjugates of scutellarein in rat plasma. Plasma samples were pretreated by protein precipitation with acetonitrile. The analytes (scutellarin, scutellarein-6,7-di-O-β-D-glucuronide and scutellarein-6-O-β-D- glucuronide), together with internal standard (IS, baicalin) were separated on a Diamonsil C18 column (150 mm × 4.6 mm, 5 μm) with an isocratic mobile phase consisting of methanol–water − formic acid (55:45:0.2, v/v/v). Mass spectrometric detection was performed by selected reaction monitoring (SRM) mode via electrospray ionization source operating in negative ionization mode. The method was linear for all the analytes over the investigated concentration ranges with correlation coefficients greater than 0.9954. The intra- and inter-day precisions were less than 9.1% and the accuracy was between–1.7% and 4.2%. The extraction recoveries of the analytes and IS from rat plasma were over 63.7%. The validated method has been successfully applied to a pharmacokinetic study of breviscapine in rats after intragastric administration at a dose of 20 mg/kg. The pharmacokinetic results would be helpful to better understand the pharmacological action mechanism of breviscapineJournal of Chromatography B 08/2014; 965. DOI:10.1016/j.jchromb.2014.06.013 · 2.73 Impact Factor
Article: Triterpenoid Saponins from the Roots of Clematis argentilucida and Their Cytotoxic Activity[Show abstract] [Hide abstract]
ABSTRACT: The reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of four new oleanane-type triterpenoid saponins, 1-4, four known saponins, 5-8, first isolated from the species, together with ten saponins, 9-18, reported in the preceding papers. The structures of saponins 1-8 were elucidated by extensive spectroscopic analysis and chemical evidences. The cytotoxicity of all the saponins were evaluated against human tumor HL-60, HepG-2, and SGC-7901 cell lines. The monodesmosidic saponins 4, 7, 8, and 14-18 exhibited cytotoxic activity against the three cell lines with IC50 values in the range of 0.87-19.48 µM.Planta Medica 07/2014; 80(11). DOI:10.1055/s-0034-1382838 · 2.15 Impact Factor
Article: Simultaneous determination of nine major constituents in Agrimonia pilosa Ledeb. by HPLC-DAD-ESI-MS/MS[Show abstract] [Hide abstract]
ABSTRACT: Herba Agrimoniae is a traditional Chinese medicine. To date, there is no quantitative control method for Agrimonia pilosa (A. pilosa) with main active constituent contents listed in the Chinese Pharmacopeia. A high performance liquid chromatography coupled with diode-array detection and electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI-MS/MS) method is established for the characterization and simultaneous quantification of nine major constituents in A. pilosa. Furthermore, the contents of these constituents of A. pilosa from 21 different regions of China were analyzed and compared. All calibration curves show good linearity (r ≥ 0.999). The HPLC-DAD method shows good precision, repeatability and stability for the quantification of the nine constituents in A. pilosa with the standard deviations below 3.29%. The recoveries for the quantified constituents are within the range of 95.44-102.55%. The qualitative and quantitative method was proved to be sensitive, accurate and reliable to determine the constituents in A. pilosa. The method is successfully applied to differentiate the A. pilosa of different regions.Analytical methods 06/2014; 6(12):4373. DOI:10.1039/c4ay00042k · 1.82 Impact Factor
Article: Nitric Oxide Induces Apoptosis and Autophagy; Autophagy Down-regulates NO Synthesis in Physalin A-treated A375-S2 Human Melanoma Cells.[Show abstract] [Hide abstract]
ABSTRACT: Physalin A is an active withanolide isolated from Physalis alkekengi var. franchetii, a traditional Chinese herbal medicine named Jindenglong, which has been used for the treatment of sore throat, hepatitis, eczema and tumors in China. Our previous study demonstrated that physalin A induced apoptosis and cyto-protective autophagy in A375-S2 human melanoma cells. Induction of reactive oxygen species (ROS) with physalin A triggered apoptosis. In this study, NO generated by physalin A induced apoptosis and autophagy in A375-S2 cells, since physalin A induced the expression of inducible nitric oxide synthase (iNOS) in the cells. Generation of NO partially promoted both apoptosis and autophagy in A375-S2 cells. NO suppressed mTOR expression, which led to autophagy induction. An autophagic inhibitor, 3-methyladenine (3MA) promoted NO production, while acceleration of autophagy with an autophagic agonist rapamycin repressed NO production, suggesting that autophagy and NO production form a negative feedback loop that eventually protects the cells from apoptosis. The results together with the previous study indicate apoptosis and autophagy induced by physalin A in A375-S2 cells; the autophagy, repressing production of reactive nitrogen species (RNS) and ROS, protects the cells from apoptosis.Food and Chemical Toxicology 06/2014; 71. DOI:10.1016/j.fct.2014.06.007 · 2.90 Impact Factor
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ABSTRACT: One new monoterpenoid glycoside (1), together with seven known compounds, including two alkaloids (2–3), three phenylpropanoids (4–6), and two nucleosides (7–8) were isolated from the calyces of Physalis alkekengi var. franchetii. Their structures were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. These eight compounds were isolated for the first time from the genus Physalis. The chemotaxonomic significance of these compounds was summarized.Biochemical Systematics and Ecology 06/2014; 54:31–35. DOI:10.1016/j.bse.2013.12.030 · 0.97 Impact Factor
Article: Indole alkaloids from the roots of Isatis indigotica and their inhibitory effects on nitric oxide production[Show abstract] [Hide abstract]
ABSTRACT: Three rare indole-2-S-glycosides, indole-3-acetonitrile-2-S-β-D-glucopyranoside (1), indole-3-acetonitrile-4-methoxy-2-S-β-D-glucopyranoside (2) and N-methoxy-indole-3-acetonitrile-2-S-β-D-glucopyranoside (3), together with 11 known indole alkaloids were isolated from the roots of Isatis indigotica Fort. (Cruciferae). The structures of 1-3 were elucidated on the basis of mass spectrometry and extensive 1D and 2D NMR spectroscopy. All of the isolated compounds were tested for inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages. A plausible biosynthesis pathway of 1-3 is also proposed.Fitoterapia 06/2014; 95. DOI:10.1016/j.fitote.2014.03.019 · 2.35 Impact Factor
Top Journals
Tianjin University of Traditional Chinese MedicineT'ien-ching-shih, Tianjin Shi, China
Shenyang Pharmaceutical University
Feng-t'ien, Liaoning, China
- • Department of Natural Products Chemistry
- • School of Traditional Chinese Medicines
- • School of Traditional Chinese Materia Medica
Shandong UniversityChi-nan-shih, Shandong Sheng, China
University of Jinan (Jinan, China)Chi-nan-shih, Shandong Sheng, China


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