JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Asymmetric Hetero-Diels-Alder Reaction of Diazenes Catalyzed by Chiral Silver Phosphate: Water Participates in the Catalysis and Stereocontrol.
Org. Lett.
PUBLISHED: 11-20-2014
Show Abstract
Hide Abstract
The chiral silver phosphate was confirmed to efficiently catalyze a highly regio- and enantioselective hetero-Diels-Alder reaction of diazenes to furnish piperazine derivatives in high yields and excellent ee values. DFT calculations revealed that the water molecule participates in the catalysis by coordination to silver phosphate and also found that the hydroxy group of 1-hydroxy-2,3-hexadiene not only formed a hydrogen bond with the oxygen of phosphate but also coordinated to the Ag(I) to simultaneously stabilize the transition states and control the regioselectivity.
Related JoVE Video
New Risk Factors for Adult Onset Incident Asthma: A Nested Case Control Study of Host Antioxidant Defense.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 11-20-2014
Show Abstract
Hide Abstract
Rationale: Host antioxidant defense, consisting of enzymatic antioxidant activity and non-enzymatic antioxidant micronutrients, is implicated in asthma pathogenesis. Studies of antioxidant defense and adult incident asthma have either used measures of antioxidants estimated from questionnaires or not considered enzymatic aspects of host defense. Objective: We conducted the first study designed and powered to investigate the association of antioxidant defenses on adult incident asthma. Methods: In a nested case-control study, we followed Shanghai women (ages 40-70) without prevalent asthma at baseline, over eight years. Incident asthmatics were ascertained prospectively by gold standard testing of symptomatic women and matched to two asymptomatic controls. Measurements: Baseline urinary F2-isoprostanes, plasma concentrations of antioxidant micronutrients (tocopherols, xanthins, carotenes, and lycopene) and antioxidant enzyme activity (platelet-activating factor acetylhydrolase [PAF-AH] and superoxide dismutase) were measured from samples collected prior to disease onset. Main Results: Among 65,372 women, 150 (0.24%) developed asthma. F2-isoprostane levels prior to asthma onset were not different between cases and controls. Doubling of ?-tocopherol concentrations and PAF-AH activity was associated with 50% and 37% decreased risk of incident asthma (adjusted OR; 95% confidence interval [OR; 95%CI], ?-tocopherol OR= 0.52; 95%CI: 0.32-0.84; PAF-AH OR=0.63; 95%CI:0.42-0.93). Conclusions: In this prospective study ?-tocopherol, within normal reference ranges, and PAF-AH enzymatic activity, were associated with decreased asthma development. These modifiable risk factors may be an effective strategy to test for primary asthma prevention.
Related JoVE Video
Hybrids of Phenylsulfonylfuroxan and Coumarin as Potent Antitumor Agents.
J. Med. Chem.
PUBLISHED: 10-29-2014
Show Abstract
Hide Abstract
Sixteen furoxan-based nitric oxide (NO) releasing coumarin derivatives (6a-c, 8a-g, 10a, 13a,b, 15, and 17a,b) were designed, synthesized, and evaluated against the A549, HeLa, A2780, A2780/CDDP, and HUVEC cell lines. Most derivatives displayed potent antiproliferation activities. Among them, 8b exhibited the strongest antiproliferation activity on the four sensitive cell lines mentioned above and three drug resistant tumor cell lines A2780/CDDP, MDA-MB-231/Gem, and SKOV3/CDDP with IC50 values from 14 to 53 nM and from 62 to 140 nM, respectively. Furthermore, 8b inhibited the growth of A2780 in vivo and displayed lower toxicity on nontumorigenesis T29, showing good selectivity against malignant cells in vitro. Preliminary pharmacological studies showed that 8b induces apoptosis, arrests the cell cycle at the G2/M phase in the A2780 cell line, and disrupts the phosphorylation of MEK1 and ERK1. Overall, the NO-releasing capacity and the inhibition of ERK/MAPK pathway signaling may explain the potent antineoplastic activity of these compounds.
Related JoVE Video
Higher Dietary Choline Intake Is Associated with Lower Risk of Nonalcoholic Fatty Liver in Normal-Weight Chinese Women.
J. Nutr.
PUBLISHED: 10-15-2014
Show Abstract
Hide Abstract
Choline deficiency has been shown to induce liver fat accumulation in both rodent and human studies. However, it is unclear whether dietary choline intake is related to fatty liver in the general population.
Related JoVE Video
Human metabolic correlates of body mass index.
Metabolomics
PUBLISHED: 09-26-2014
Show Abstract
Hide Abstract
A high body mass index (BMI) is a major risk factor for several chronic diseases, but the biology underlying these associations is not well-understood. Dyslipidemia, inflammation, and elevated levels of growth factors and sex steroid hormones explain some of the increased disease risk, but other metabolic factors not yet identified may also play a role.
Related JoVE Video
Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 09-11-2014
Show Abstract
Hide Abstract
Levels of the cyclooxygenase 2 (COX2) enzyme are elevated in breast cancer tissue, and most COX2 effects are believed to be mediated through overproduction of prostaglandin E2 (PGE2). We evaluated associations between the primary urinary metabolite of PGE2 (PGE-M) and breast cancer risk.
Related JoVE Video
Tetramethoxychalcone, a chalcone derivative, suppresses proliferation, blocks cell cycle progression, and induces apoptosis of human ovarian cancer cells.
PLoS ONE
PUBLISHED: 09-02-2014
Show Abstract
Hide Abstract
In the present study, we investigated the in vitro antitumor functions of a synthetic chalcone derivative 4,3',4',5'- tetramethoxychalcone (TMOC) in ovarian cancer cells. We found that TMOC inhibited the proliferation and colony formation of cisplatin sensitive cell line A2780 and resistant cell line A2780/CDDP, as well as ovarian cancer cell line SKOV3 in a time- and dose-dependent manner. Treatment of A2780 cells with TMOC resulted in G0/G1 cell cycle arrest through the down-regulation of cyclin D1 and CDK4, and the up-regulation of p16, p21 and p27 proteins. We demonstrated that TMOC might induce cell apoptosis through suppressing Bcl-2 and Bcl-xL, but enhancing the expression of Bax and the cleavage of PARP-1. Treatment of TMOC also reduced the invasion and migration of A2780 cells. Finally, we found that TMOC inhibited the constitutive activation of STAT3 signaling pathway and induced the expression of the tumor suppressor PTEN regardless of the p53 status in cell lines. These data suggest that TMOC may be developed as a potential chemotherapeutic agent to effectively treat certain cancers including ovarian cancer.
Related JoVE Video
C-H functionalization/asymmetric Michael addition cascade enabled by relay catalysis: metal carbenoid used for C-C bond formation.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-21-2014
Show Abstract
Hide Abstract
A combination of either ruthenium(II) or rhodium(II) complexes and quinine-derived squaramide enables 3-diazooxindoles, indoles, and nitroalkenes to undergo highly efficient asymmetric three-component reactions, thus affording optically active 3,3'-bis(indole)s through a consecutive C-C bond-forming sequence, which turned out to be applicable to the facile total synthesis of (-)-folicanthine.
Related JoVE Video
Association of Leukocyte Mitochondrial DNA Copy Number with Colorectal Cancer Risk: Results from the Shanghai Women's Health Study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 08-19-2014
Show Abstract
Hide Abstract
Mitochondria play an important role in cellular energy metabolism, free radical production, and apoptosis, and thus may be involved in cancer development.
Related JoVE Video
Chiral Counteranion Strategy for Asymmetric Oxidative C(sp(3) )?H/C(sp(3) )?H Coupling: Enantioselective ?-Allylation of Aldehydes with Terminal Alkenes.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-13-2014
Show Abstract
Hide Abstract
The first enantioselective ?-allylation of aldehydes with terminal alkenes has been realized by combining asymmetric counteranion catalysis and palladium-catalyzed allylic C?H activation. This method can tolerate a wide scope of ?-branched aromatic aldehydes and terminal alkenes, thus affording allylation products in high yields and with good to excellent levels of enantioselectivity. Importantly, the findings suggest a new strategy for the future creation of enantioselective C?H/C?H coupling reactions.
Related JoVE Video
Correlates of self-reported dietary cruciferous vegetable intake and urinary isothiocyanate from two cohorts in China.
Public Health Nutr
PUBLISHED: 08-08-2014
Show Abstract
Hide Abstract
To assess correlations between cruciferous vegetable intake and urinary isothiocyanate (ITC) level, in addition to glutathione S-transferase (GST) genotypes and other individual factors.
Related JoVE Video
0346?Occupational exposure to lead and cancer in two cohort studies of men and women in shanghai, china.
Occup Environ Med
PUBLISHED: 07-15-2014
Show Abstract
Hide Abstract
Epidemiologic studies of occupational lead exposure have suggested increased risks of cancers of the brain, kidney, lung, meninges, and stomach; however, the totality of the evidence is inconsistent. To clarify whether lead is a carcinogen, we investigated the relationship between occupational lead exposure and risks of these five cancer sites in two prospective cohort studies in Shanghai, China.
Related JoVE Video
0324? Occupational exposure to benzene and risk of non-Hodgkin lymphoma in a population-based cohort study of Chinese women in Shanghai0324? Occupational exposure to benzene and risk of non-Hodgkin lymphoma in a population-based cohort study of Chinese women in Shanghai
Occup Environ Med
PUBLISHED: 07-15-2014
Show Abstract
Hide Abstract
The association between benzene exposure and non-Hodgkin lymphoma (NHL) has been the subject of debate, and an IARC working group recently concluded for the first time that there is now limited evidence to support this association in humans. We evaluated the relationship between occupational benzene exposure and NHL risk among 73 087 women in a population-based cohort study of women in Shanghai.
Related JoVE Video
Pre-existing type 2 diabetes and risk of lung cancer: a report from two prospective cohort studies of 133?024 Chinese adults in urban Shanghai.
BMJ Open
PUBLISHED: 07-05-2014
Show Abstract
Hide Abstract
Observational studies of type 2 diabetes (T2D) and lung cancer risk are limited and controversial. We thus examined the association between T2D and risk of incident lung cancer using a cohort design.
Related JoVE Video
Gold-catalyzed [1,5]-hydride shift onto unactivated alkynes to trigger an intermolecular Diels-Alder reaction.
Org. Lett.
PUBLISHED: 07-02-2014
Show Abstract
Hide Abstract
A [1,5]-hydride shift of sp(3) C-H onto an unactivated carbon-carbon triple bond catalyzed by a gold(I) complex enabled N-propargylisoindolines to be latent dienes and therefore triggered an intermolecular Diels-Alder reaction with dienophiles. This protocol provides an atom-economical and straightforward approach to access a wide range of polycyclic skeletons in high yields and with excellent diastereoselectivities from easily accessible molecules.
Related JoVE Video
Adherence to dietary guidelines and mortality: a report from prospective cohort studies of 134,000 Chinese adults in urban Shanghai.
Am. J. Clin. Nutr.
PUBLISHED: 06-18-2014
Show Abstract
Hide Abstract
A higher adherence to dietary recommendations, such as the Dietary Approaches to Stop Hypertension (DASH) and the Alternative Healthy Eating Index (AHEI), has been associated with lower morbidity and mortality from chronic diseases in Western populations. However, the health benefits of following the Dietary Guidelines for Chinese remain unknown.OBJECTIVE: We examined adherence to the Chinese Food Pagoda (CHFP) in association with total and cause-specific mortality and compared associations with those of the DASH and AHEI.DESIGN: Participants included 61,239 men and 73,216 women (aged 40-74 y) from 2 population-based prospective studies in Shanghai, China. Habitual dietary intakes were assessed at baseline in-person interviews by using validated food-frequency questionnaires. Deaths and underlying causes were identified through the Shanghai Vital Statistics Registry and follow-up home visits.RESULTS: We documented 2954 deaths in men and 4348 deaths in women during mean follow-ups of 6.5 and 12.0 y, respectively. A higher CHFP score was associated with lower total mortality with multivariable-adjusted HRs of 0.67 (95% CI: 0.60, 0.75) in men and 0.87 (95% CI: 0.80, 0.95) in women when extreme quartiles were compared (both P-trend < 0.005). Decreased risks associated with a higher CHFP score were observed for cardiovascular disease, cancer, and diabetes mortality, particularly in men. A significantly lower total mortality was shown for adherence to specific recommendations on vegetables, fruit, legumes, fish, and eggs but not grains, dairy, meat, fat, and salt. A higher DASH score and AHEI also predicted lower mortality from all causes, cardiovascular disease, and diabetes but not cancer.CONCLUSIONS: A greater compliance with Chinese or US dietary guidelines is associated with lower total mortality in Chinese adults. Favorable associations are more evident in men than women and more consistent for cardiometabolic mortality than cancer mortality.
Related JoVE Video
Palladium(II)/Lewis acid synergistically catalyzed allylic C-H olefination.
Org. Lett.
PUBLISHED: 06-12-2014
Show Abstract
Hide Abstract
The first allylic C-H olefination with ?-diazo esters synergistically catalyzed by a palladium(II) complex and (salen)CrCl has been established to directly generate conjugated polyene derivatives in moderate to high yields and with excellent stereoselectivities.
Related JoVE Video
Asymmetric organocatalysis combined with metal catalysis: concept, proof of concept, and beyond.
Acc. Chem. Res.
PUBLISHED: 06-09-2014
Show Abstract
Hide Abstract
Asymmetric catalysis has been considered to be the most intriguing means for building collections of functionalized optically active compounds. In particular, metal and organocatalysis have been well established to allow many fundamentally different reactions. Metal catalysis has enabled the participation of a much broader scope of chemical bonds in organic transformations than are allowed by organocatalysis, while organocatalysis permits a broader scope of functional groups to undergo a diverse range of enantioselective transformations, individually, simultaneously, or sequentially. Theoretically, the combination of organocatalysts and metal complexes could probably render new transformations through the simultaneous or sequential activation and reorganization of multiple chemical bonds if the superior features of both the catalysts are adopted. In 2001, both our research group and Takemoto's group separately described an asymmetric allylation of glycine imino esters with allyl acetate catalyzed by palladium complexes and chiral ammonium salts. In these cases, the oxidative addition of palladium complexes to allyl acetate formed the ?-allylic fragments, while the chiral ammonium salts were actually responsible for controlling the stereoselectivity. These reactions in fact marked the beginning of asymmetric organo/metal combined catalysis. Since then, asymmetric organocatalysis combined with metal catalysis, including cooperative catalysis, relay catalysis, and sequential catalysis, has been a versatile concept for the creation of unknown organic transformations. Sequential catalysis describes a one-pot reaction involving two or more incompatible catalytic cycles. Alternatively, cooperative and relay catalyses require high compatibility of principally distinct catalysts and will be the focus of this Account. The catalysts in cooperative catalytic reactions must be able to simultaneously and individually activate both substrates to drive a bond-forming reaction, while relay catalysis is basically defined as a cascade process in which two or more sequential bond-forming transformations are independently catalyzed by distinct catalysts. In the past decade, we have discovered a variety of binary catalytic systems consisting of metals, including Rh(II), Pd(0), Au(I), and Mg(II), and chiral organocatalysts, including chiral phosphoric acids and quinine-based bifunctional molecules, for cooperative catalysis and relay catalysis, allowing the accomplishment of many unprecedented asymmetric transformations. In this Account, these achievements will be summarized, particularly focusing on the description of the concept and proof of the concept, to demonstrate the robustness of combined organo/metal catalysis in the creation of efficient enantioselective transformations. In addition, elegant studies from other laboratories using chiral phosphoric acid/Au(I) for the establishment of asymmetric cascade reactions involving the carbon-carbon triple bond functionality and typical combined organo/metal catalytic systems, very recently disclosed, will also be highlighted.
Related JoVE Video
Vitamin E intake and the lung cancer risk among female nonsmokers: A report from the Shanghai Women's Health Study.
Int. J. Cancer
PUBLISHED: 05-20-2014
Show Abstract
Hide Abstract
Vitamin E includes several tocopherol isoforms, which may reduce lung cancer risk, but past studies evaluating the association between vitamin E intake and lung cancer risk were inconsistent. We prospectively investigated the associations between tocopherol intake from diet and from supplements with lung cancer risk among 72,829 Chinese female nonsmokers aged 40-70 years and participating in the Shanghai Women's Health Study (SWHS). Dietary and supplement tocopherol exposure was assessed by a validated food-frequency questionnaire at baseline and reassessed for change in intake during follow-up. Cox proportional hazards models with time-dependent covariates were used to calculate multivariate-adjusted hazard ratios (HRs) and 95% confidence interval (CIs) for lung cancer. After 12.02 years of follow-up, 481 women were diagnosed with lung cancer. Total dietary tocopherol was inversely associated with lung cancer risk among women meeting dietary guidelines for adequate intake (AI) of tocopherol (14 mg/day or more: HR: 0.78; 95% CI 0.60-0.99; compared with the category less than AI). The protective association between dietary tocopherol intake and lung cancer was restricted to women exposed to side-stream smoke in the home and workplace [HR?=?0.53 (0.29-0.97), p-trend?=?0.04]. In contrast, vitamin E supplement use was associated with increased lung cancer risk (HR: 1.33; 95% CI: 1.01-1.73), more so for lung adenocarcinoma risk (HR: 1.79; 95% CI: 1.23-2.60). In summary, dietary tocopherol intake may reduce the risk of lung cancer among female nonsmokers; however, supplements may increase lung adenocarcinoma risk and requires further investigation.
Related JoVE Video
One-carbon metabolism dietary factors and distal gastric cancer risk in chinese women.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 04-30-2014
Show Abstract
Hide Abstract
Previous studies on the association between one-carbon dietary factors and gastric cancer risk have been inconsistent.
Related JoVE Video
Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
Nat. Genet.
PUBLISHED: 04-21-2014
Show Abstract
Hide Abstract
Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 × 10(-8) to 9.22 × 10(-21)) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways.
Related JoVE Video
The negative interplay between Aurora A/B and BRCA1/2 controls cancer cell growth and tumorigenesis via distinct regulation of cell cycle progression, cytokinesis, and tetraploidy.
Mol. Cancer
PUBLISHED: 04-16-2014
Show Abstract
Hide Abstract
It is well known that the activation of Aurora A/B (Aur A/B) or inactivation of BRCA1/2 induces tumor formation. Others and we have reported that the mutual suppression between Aur A/B and BRCA1/2 may manipulate cancer cell growth and tumorigenesis, however, the interactive regulation and mechanism between these molecules are still elusive. In this study, by consecutive silencing of Aur A/B or/and BRCA1/2 with specific shRNAs, we showed that, in BRCA2-deficient pancreatic cancer cell line Capan-1 and in ovarian cancer cell line OVCA433, Aur A/B and BRCA1/2 inversely regulated the expression of each other likely through proteasome-mediated proteolysis but not through gene transcription. Aur A/B and BRCA1/2 conversely regulated cell cycle progression mainly through control of p53 and cyclin A. Moreover, the disruption of Aur A/B blocked abnormal cytokinesis and decreased cell multinuclearity and chromosome tetraploidy, whereas the deprivation of BRCA1/2 promoted the abnormal cytokinesis and enhanced the cell multinuclearity and tetraploidy. Furthermore, we showed by animal assays that the depletion of Aur A/B inhibited tumor growth of both cell lines, while the knockdown of BRCA1/2 promoted the tumor growth. However, the concurrent silencing of Aur A/B and BRCA1/2 diminished the effects of these molecules on the regulation of cell cycle, cytokinesis, and tetraploidy, leading to the burdened tumor sizes similar to those induced by scrambled shRNA-treated control cells. In summary, our study revealed that the negative interplay between Aur A/B and BRCA1/2 inversely controls the cell proliferation, cell cycle progression, cell multinuclearity, and tetraploidization to modulate tumorigenesis.
Related JoVE Video
Nonexercise physical activity and inflammatory and oxidative stress markers in women.
J Womens Health (Larchmt)
PUBLISHED: 04-15-2014
Show Abstract
Hide Abstract
Leisure time exercise has been linked to lower circulating levels of inflammatory markers. Few studies have examined the association of nonexercise physical activity with markers of inflammation and oxidative stress.
Related JoVE Video
Asymmetric synthesis of heteroaryl atropisomers via a gold-catalyzed cycloisomerization-amination cascade reaction.
Chem. Commun. (Camb.)
PUBLISHED: 04-09-2014
Show Abstract
Hide Abstract
The chiral gold(i) complex enables enantioselective cycloisomerization-amination of 2-(alkynyl)phenyl boronic acids and diazenes in high yields. A wide scope of substrates bearing various functional groups was tolerated to generate structurally different hydrazide derivatives as a new type of atropisomer.
Related JoVE Video
Sleep Duration and Mortality: A Prospective Study of 113 138 Middle-Aged and Elderly Chinese Men and Women.
Sleep
PUBLISHED: 04-07-2014
Show Abstract
Hide Abstract
To evaluate associations of sleep duration with total mortality and disease-specific mortality in a Chinese population.
Related JoVE Video
Urinary biomarkers of oxidative stress and breast cancer survival.
Cancer Causes Control
PUBLISHED: 03-21-2014
Show Abstract
Hide Abstract
Systemic oxidative stress has been implicated in the pathogenesis and progression of many chronic diseases, including breast cancer. No studies have investigated F2-isoprostanes (F2-IsoPs), valid biomarkers of systemic oxidative stress, in association with breast cancer prognosis. We conducted a nested case-control study in a prospective breast cancer survivor cohort to investigate systemic oxidative stress and survival.
Related JoVE Video
Predictors and variability of repeat measurements of urinary phenols and parabens in a cohort of shanghai women and men.
Environ. Health Perspect.
PUBLISHED: 03-20-2014
Show Abstract
Hide Abstract
Exposure to certain phenols is ubiquitous because of their use in many consumer and personal care products. However, predictors of exposure have not been well characterized in most populations.
Related JoVE Video
Cruciferous vegetable intake is inversely correlated with circulating levels of proinflammatory markers in women.
J Acad Nutr Diet
PUBLISHED: 03-13-2014
Show Abstract
Hide Abstract
Higher intakes of cruciferous vegetables or their constituents have been shown to lower inflammation in animal studies. However, evidence for this anti-inflammatory effect of cruciferous vegetable consumption in humans is scarce.
Related JoVE Video
The function of EMSY in cancer development.
Tumour Biol.
PUBLISHED: 03-09-2014
Show Abstract
Hide Abstract
EMSY was first reported to bind BRCA2 and to inactivate the function of BRCA2, leading to the development of sporadic breast and ovarian cancers. The function of EMSY may also be involved in DNA damage repair, genomic instability, and chromatin remolding. Recent studies have shown that amplification of EMSY was also associated with other cancers such as prostate and pancreatic cancers and linked to tumor phenotypes and clinical outcomes. By reviewing literatures published since 2003, here, we have summarized the recent advances of EMSY in cancer development.
Related JoVE Video
The chemokine receptor-CXCR2 plays a critical role in the invasion and metastases of oral squamous cell carcinoma in vitro and in vivo.
J. Oral Pathol. Med.
PUBLISHED: 02-26-2014
Show Abstract
Hide Abstract
Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world with about 50% survival rate over 5 years. OSCC has a highly invasive potency and frequently metastasizes to the cervical lymph nodes, which is the principle reason leading to poor prognosis. CXCR2, the receptor of CXC chemokines, has been reported to be involved in invasion and metastasis in multiple types of malignancy. However, the accurate role of CXCR2 in OSCC has been little noticed.
Related JoVE Video
Cholelithiasis and the risk of liver cancer: results from cohort studies of 134,546 Chinese men and women.
J Epidemiol Community Health
PUBLISHED: 02-26-2014
Show Abstract
Hide Abstract
Cholelithiasis and cholecystectomy have been proposed as risk factors for liver cancer, but findings have been inconsistent. We assessed this association using data from the Shanghai Women's and Men's Health Studies.
Related JoVE Video
Asymmetric organocatalytic direct C(sp²)-H/C(sp³)-H oxidative cross-coupling by chiral iodine reagents.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 02-19-2014
Show Abstract
Hide Abstract
An asymmetric organocatalytic direct C-H/C-H oxidative coupling reaction of N(1),N(3)-diphenylmalonamides has been well established by using chiral organoiodine compounds as catalysts, wherein four C-H bonds were stereoselectively functionalized to give structurally diverse spirooxindoles with high levels of enantioselectivity. More importantly, the findings indicated that chiral hypervalent organoiodine reagents can serve as alternative catalysts for the creation of enantioselective functionalization of inactive C-H bonds.
Related JoVE Video
Regulation of proximal tubule vacuolar H(+)-ATPase by PKA and AMP-activated protein kinase.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 02-19-2014
Show Abstract
Hide Abstract
The vacuolar H(+)-ATPase (V-ATPase) mediates ATP-driven H(+) transport across membranes. This pump is present at the apical membrane of kidney proximal tubule cells and intercalated cells. Defects in the V-ATPase and in proximal tubule function can cause renal tubular acidosis. We examined the role of protein kinase A (PKA) and AMP-activated protein kinase (AMPK) in the regulation of the V-ATPase in the proximal tubule as these two kinases coregulate the V-ATPase in the collecting duct. As the proximal tubule V-ATPases have different subunit compositions from other nephron segments, we postulated that V-ATPase regulation in the proximal tubule could differ from other kidney tubule segments. Immunofluorescence labeling of rat ex vivo kidney slices revealed that the V-ATPase was present in the proximal tubule both at the apical pole, colocalizing with the brush-border marker wheat germ agglutinin, and in the cytosol when slices were incubated in buffer alone. When slices were incubated with a cAMP analog and a phosphodiesterase inhibitor, the V-ATPase accumulated at the apical pole of S3 segment cells. These PKA activators also increased V-ATPase apical membrane expression as well as the rate of V-ATPase-dependent extracellular acidification in S3 cell monolayers relative to untreated cells. However, the AMPK activator AICAR decreased PKA-induced V-ATPase apical accumulation in proximal tubules of kidney slices and decreased V-ATPase activity in S3 cell monolayers. Our results suggest that in proximal tubule the V-ATPase subcellular localization and activity are acutely coregulated via PKA downstream of hormonal signals and via AMPK downstream of metabolic stress.
Related JoVE Video
Fenofibrate induces apoptosis of triple-negative breast cancer cells via activation of NF-?B pathway.
BMC Cancer
PUBLISHED: 02-12-2014
Show Abstract
Hide Abstract
There are a lot of unmet needs in patients with triple-negative breast cancer (TNBC). Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-?) agonist, has been used for decades to treat hypertriglyceridaemia and mixed dyslipidaemia. Recent studies show that it might have anti-tumor effects, however, the mechanism remains unclear. Here, we assessed the ability of fenofibrate to induce apoptosis of TNBC in vitro and in vivo and explored involved mechanisms.
Related JoVE Video
The polymorphism interleukin-8 -251A/T is associated with a significantly increased risk of cancers from a meta-analysis.
Tumour Biol.
PUBLISHED: 02-11-2014
Show Abstract
Hide Abstract
Emerging evidences show that interleukin-8 (IL-8) has important regulatory functions in tumorigenesis. IL-8 -251A/T is a single nucleotide polymorphism in the promoter region of the IL-8 gene and affects IL-8 production. Analysis of previous studies on the association of -251A/T polymorphism with different cancer types remained to be illustrated. To further assess the effect of -251A/T polymorphism on cancer risks, we performed this meta-analysis, up to November 2013, of 12,917 cases with different cancer types and 17,689 controls from 47 published case-control designed studies. Statistical analyses were performed using STATA 11.0 software. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. ORs with 95 % CIs for IL-8 -251A/T polymorphism and cancer were estimated using fixed- and random-effects models when appropriate. Significantly increased risks were found in overall under the models of A allele vs. T allele, AA vs. TT, and AA vs. AT/TT. Significantly elevated risks were observed in breast cancer under the models of A allele vs. T allele, AT vs. TT, AA/AT vs. TT, and AA vs. AT/TT, and in nasopharyngeal carcinoma under the models of AT vs. TT, AA/AT vs. TT, and AA vs. AT/TT. We found that significantly elevated risks were observed in the Asian population and hospital-based studies in all comparison models. Thus, this meta-analysis indicates that IL-8 -251A/T polymorphism is associated with a significantly increased risk of cancers and may provide evidence-based medical certificate to study the cancer susceptibility.
Related JoVE Video
Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East Asians.
Int. J. Cancer
PUBLISHED: 01-29-2014
Show Abstract
Hide Abstract
Genome-wide association studies (GWAS) of colorectal cancer (CRC) have been conducted primarily in European descendants. In a GWAS conducted in East Asians, we first analyzed approximately 1.7 million single-nucleotide polymorphisms (SNPs) in four studies with 1,773 CRC cases and 2,642 controls. We then selected 66 promising SNPs for replication and genotyped them in three independent studies with 3,612 cases and 3,523 controls. Five SNPs were further evaluated using data from four additional studies including up to 3,290 cases and 4,339 controls. SNP rs7229639 in the SMAD7 gene was found to be associated with CRC risk with an odds ratio (95% confidence interval) associated with the minor allele (A) of 1.22 (1.15-1.29) in the combined analysis of all 11 studies (p = 2.93 × 10(-11) ). SNP rs7229639 is 2,487 bp upstream from rs4939827, a risk variant identified previously in a European-ancestry GWAS in relation to CRC risk. However, these two SNPs are not correlated in East Asians (r(2) ?= 0.008) nor in Europeans (r(2) ?= 0.146). The CRC association with rs7229639 remained statistically significant after adjusting for rs4939827 as well as three additional CRC risk variants (rs58920878, rs12953717 and rs4464148) reported previously in this region. SNPs rs7229639 and rs4939827 explained approximately 1% of the familial relative risk of CRC in East Asians. This study identifies a new CRC risk variant in the SMAD7 gene, further highlighting the significant role of this gene in the etiology of CRC.
Related JoVE Video
Aurora-A controls cancer cell radio- and chemoresistance via ATM/Chk2-mediated DNA repair networks.
Biochim. Biophys. Acta
PUBLISHED: 01-17-2014
Show Abstract
Hide Abstract
High expression of Aurora kinase A (Aurora-A) has been found to confer cancer cell radio- and chemoresistance, however, the underlying mechanism is unclear. In this study, by using Aurora-A cDNA/shRNA or the specific inhibitor VX680, we show that Aurora-A upregulates cell proliferation, cell cycle progression, and anchorage-independent growth to enhance cell resistance to cisplatin and X-ray irradiation through dysregulation of DNA damage repair networks. Mechanistic studies showed that Aurora-A promoted the expression of ATM/Chk2, but suppressed the expression of BRCA1/2, ATR/Chk1, p53, pp53 (Ser15), H2AX, ?H2AX (Ser319), and RAD51. Aurora-A inhibited the focus formation of ?H2AX in response to ionizing irradiation. Treatment of cells overexpressing Aurora-A and ATM/Chk2 with the ATM specific inhibitor KU-55933 increased the cell sensitivity to cisplatin and irradiation through increasing the phosphorylation of p53 at Ser15 and inhibiting the expression of Chk2, ?H2AX (Ser319), and RAD51. Further study revealed that BRCA1/2 counteracted the function of Aurora-A to suppress the expression of ATM/Chk2, but to activate the expression of ATR/Chk1, pp53, ?H2AX, and RAD51, leading to the enhanced cell sensitivity to irradiation and cisplatin, which was also supported by the results from animal assays. Thus, our data provide strong evidences that Aurora-A and BRCA1/2 inversely control the sensitivity of cancer cells to radio- and chemotherapy through the ATM/Chk2-mediated DNA repair networks, indicating that the DNA repair molecules including ATM/Chk2 may be considered for the targeted therapy against cancers with overexpression of Aurora-A.
Related JoVE Video
An organocatalytic asymmetric allylic alkylation allows enantioselective total synthesis of hydroxymetasequirin-A and metasequirin-B tetramethyl ether diacetates.
Org. Lett.
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
The first highly stereoselective organocatalytic intermolecular allylic alkylation of allylic alcohols with 1,3-dicarbonyls has been developed to allow the first enantioselective total synthesis of hydroxymetasequirin-A and metasequirin-B tetramethyl ether diacetates.
Related JoVE Video
Neuromechanism Study of Insect-Machine Interface: Flight Control by Neural Electrical Stimulation.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The insect-machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: ?-lobe (or ?-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee-machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control.
Related JoVE Video
Polycyclic aromatic hydrocarbons and risk of gastric cancer in the Shanghai Women's Health Study.
Int J Mol Epidemiol Genet
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Polycyclic aromatic hydrocarbons (PAHs) are byproducts of incomplete combustion of organic materials. Sources include tobacco smoke, charbroiled meat, and air pollution. Indirect evidence suggests that PAHs may be associated with carcinogenesis, but the association with gastric cancer is unclear.
Related JoVE Video
Age at menarche and natural menopause and number of reproductive years in association with mortality: results from a median follow-up of 11.2 years among 31,955 naturally menopausal Chinese women.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Studies conducted in Western countries suggest that early age at menarche and early age at menopause are both associated with increased total mortality, but limited data are available for Asian populations. We examined associations of age at menarche and natural menopause and duration of the reproductive span with mortality in a population-based cohort study of Chinese women.
Related JoVE Video
Impact of premature ovarian failure on mortality and morbidity among Chinese women.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
To evaluate associations of premature ovarian failure (POF) with mortality and morbidity in Asian populations.
Related JoVE Video
Catalytic cascade hydroalkoxylation/isomerization/ [4 + 2] cycloaddition using enyne alcohols as latent dienes or dienophiles.
Org. Biomol. Chem.
PUBLISHED: 11-01-2013
Show Abstract
Hide Abstract
Enyne alcohols can react as precursors of either dienes or dienophiles with different substrates after hydroxylation and isomerization by gold catalysis. As such, oxa-bridged tricyclo[5.2.2.02,6]-undec-8-ene-3,5-dione derivatives have been obtained by the Diels–Alder reaction and tetrahydro-1H-furo[3,4-c]pyran derivatives could be accessed by the hetero-Diels–Alder cycloaddition.
Related JoVE Video
Dietary carbohydrates, refined grains, glycemic load, and risk of coronary heart disease in Chinese adults.
Am. J. Epidemiol.
PUBLISHED: 09-05-2013
Show Abstract
Hide Abstract
The potential long-term association between carbohydrate intake and the risk of coronary heart disease (CHD) remains unclear, especially among populations who habitually have high-carbohydrate diets. We prospectively examined intakes of carbohydrates and staple grains as well as glycemic index and glycemic load in relation to CHD among 117,366 Chinese women and men (40-74 years of age) without history of diabetes, CHD, stroke, or cancer at baseline in Shanghai, China. Diet was assessed using validated food frequency questionnaires. Incident CHD cases were ascertained during follow-ups (in women, the mean was 9.8 years and in men, the mean was 5.4 years) and confirmed by medical records. Carbohydrate intake accounted for 67.5% of the total energy intake in women and 68.5% in men. Seventy percent of total carbohydrates came from white rice and 17% were from refined wheat products. Positive associations between carbohydrate intakess and CHD were found in both sexes (all P for heterogeneity > 0.35). The combined multivariate-adjusted hazard ratios for the lowest to highest quartiles of carbohydrate intake, respectively, were 1.00, 1.38, 2.03, and 2.88 (95% confidence interval: 1.44, 5.78; P for trend = 0.001). The combined hazard ratios comparing the highest quartile with the lowest were 1.80 (95% confidence interval: 1.01, 3.17) for refined grains and 1.87 (95% confidence interval: 1.00, 3.53) for glycemic load (both P for trend = 0.03). High carbohydrate intake, mainly from refined grains, is associated with increased CHD risk in Chinese adults.
Related JoVE Video
Aurora-A: a potential DNA repair modulator.
Tumour Biol.
PUBLISHED: 08-31-2013
Show Abstract
Hide Abstract
It is well-known that overexpression of Aurora-A promotes tumorigenesis, but the role of Aurora-A in the development of cancer has not been fully investigated. Recent studies indicate that Aurora-A may confer cancer cell chemo- and radioresistance through dysregulation of cell cycle progression and DNA damage response. Direct evidences from literatures suggest that Aurora-A inhibits pRb, p53, p21(waf1/cip1), and p27(cip/kip) but enhances Plk1, CDC25, CDK1, and cyclin B1 to repeal cell cycle checkpoints and to promote cell cycle progression. Other studies indicate that Aurora-A suppresses BRCA1, BRCA2, RAD51, poly(ADP ribose) polymerase (PARP), and gamma-H2AX to dysregulate DNA damage response. Aurora-A may also interact with RAS and Myc to control DNA repair indirectly. In this review, we summarized the potential role of Aurora-A in DNA repair from the current literatures and concluded that Aurora-A may function as a DNA repair modulator to control cancer cell radio- and chemosensitivity, and that Aurora-A-associated DNA repair molecules may be considered for targeted cancer therapy.
Related JoVE Video
Gibberellin oxidase activities in Bradyrhizobium japonicum bacteroids.
Phytochemistry
PUBLISHED: 08-30-2013
Show Abstract
Hide Abstract
Bradyrhizobium japonicum bacteroids isolated from root nodules of soybean (Glycine max.) plants converted the gibberellin (GA) precursor [(14)C1]GA12 into several products identified by combined gas chromatography-mass spectrometry as [(14)C1]GA24, [(14)C1]GA9, [(14)C1]GA15, GA9 17-nor-16-one and unidentified products. The oxidation of GA12, catalyzed by the GA 20-oxidase, was present in symbiotic bacteroids from plants around flowering, but not in bacteroids from plants at either an early vegetative stage or at late growth stages. Expression of cps and ks genes, involved in ent-kaurene biosynthesis, was also demonstrated in bacteroids from soybean plants around flowering. Earlier precursors of the GA pathway, ent-[(14)C1]kaurenoic acid or [(14)C4]GA12-aldehyde, were efficiently utilized by B. japonicum bacteroids to give labelled GA9 plus intermediates partially oxidized at C-20, as well as GA9 17-nor-16-one and an unidentified product. No 3? or 13-hydroxylated [(14)C]GAs were detected in any of the incubations. Moreover the C19-GAs [(14)C1]GA4 or [(14)C1]GA20 were recovered unconverted upon incubation with the bacteroids which supports the absence of GA 3?-hydroxylase activity in B. japonicum. The bacterial 20-oxidase utilized the 13-hydroxylated substrates [(14)C1]GA53, [(14)C1]GA44 or [(14)C1]GA19, although with less efficiency than [(14)C1]GA12 to give [(14)C1]GA20 as final product, while the 3?-hydroxylated substrate [(14)C1]GA14 was converted to [(14)C1]GA4 to a very small extent. Endogenous GA9 and GA24 were identified by GC-MS in methanolic nodule extracts. These results suggest that B. japonicum bacteroids would synthesize GA9 under the symbiotic conditions present in soybean root nodules.
Related JoVE Video
Intake of specific nonfermented soy foods may be inversely associated with risk of distal gastric cancer in a Chinese population.
J. Nutr.
PUBLISHED: 08-28-2013
Show Abstract
Hide Abstract
Because the association between soy consumption and gastric cancer is inconsistent, we evaluated the putative preventive effect of soy food on gastric cancer risk in the Shanghai Womens and Mens Health Studies, comprising a total of 128,687 participants. Intake of nonfermented soy foods was estimated using 2 validated food-frequency questionnaires. HRs were calculated with 95% CIs for intake amounts of total nonfermented soy food intake, soy protein, and isoflavones as well as individual soy food groups using Cox proportional hazards regression. A total of 493 distal gastric cancer cases were identified by 2010. Although all risk estimates for summary measures of soy food intake above the lowest quartile (quartile 1) were suggestive of a protective effect, no statistically significant associations with risk of distal gastric cancer were found. Among the separate soy food groups, significant reductions in risk of distal gastric cancer by increasing intake of tofu were found in men in quartile 2 (HR: 0.59; 95% CI: 0.40, 0.86), quartile 3 (HR: 0.62; 95% CI: 0.44, 0.88), and quartile 4 (HR: 0.64; 95% CI: 0.42, 0.99), resulting in a significant trend (P-trend = 0.02). Dry bean intake was also inversely associated with decreased risk of gastric cancer, but in postmenopausal women only [quartile 2 (HR: 0.54; 95% CI: 0.30, 0.96); quartile 3 (HR: 0.90; 95% CI: 0.64, 1.27); and quartile 4 (HR: 0.63; 95% CI: 0.43, 0.91)], resulting in a significant trend (P-trend = 0.03). Overall, our study found no statistically significant association between nonfermented soy food intake and distal gastric cancer risk, though the data supported the hypothesis that tofu may protect against distal gastric cancer in men and dry bean consumption may decrease the risk of gastric cancer in postmenopausal women.
Related JoVE Video
Circulating C-reactive protein and colorectal cancer risk: a report from the Shanghai Mens Health Study.
Carcinogenesis
PUBLISHED: 08-28-2013
Show Abstract
Hide Abstract
Chronic inflammation has been implicated in the pathogenesis of colorectal cancer. The objective of this study was to evaluate the association of prediagnostic circulating levels of C-reactive protein (CRP), a biomarker of systemic inflammation, with subsequent development of colorectal cancer. Prediagnostic plasma CRP levels were examined among 288 colorectal cancer cases and 576 individually-matched controls nested within the Shanghai Mens Health Study (2002-06), a population-based cohort study of 61 482 Chinese men. The association between CRP levels and colorectal cancer risk was investigated. Baseline plasma CRP levels were 53% higher among men who subsequently developed colorectal cancer than among those who remained free of the disease (1.15 versus 0.75 ?g/ml; P < 0.001). Multivariate analyses showed a dose-dependent relationship between CRP and colorectal cancer risk (P trend = 0.003); men in the highest tertile (CRP > 1.19 ?g/ml) had 1.88-fold (95% confidence interval (CI): 1.24-2.86) increased odds of developing colorectal cancer compared with men in the lowest tertile (CRP < 0.45 ?g/ml). The association was only significant for colon cancer, when cancer site was considered, and was predominantly seen for cases diagnosed within 4 years of blood collection; adjusted odds ratios for the highest versus the lowest tertiles were 3.28 (95% CI: 1.28-8.37), 3.68 (95% CI: 1.62-8.38) and 1.05 (95% CI: 0.56-1.97), respectively, for cases diagnosed <2, 2-4 and >4 years after blood collection. The findings from our study suggest that circulating CRP level is positively associated with colorectal cancer risk in Chinese men, and this association, at least in part, is explained by inflammation-related cancerous or precancerous processes.
Related JoVE Video
Rhodium/chiral urea relay catalysis enables an enantioselective semipinacol rearrangement/Michael addition cascade.
Org. Lett.
PUBLISHED: 07-25-2013
Show Abstract
Hide Abstract
The combined use of rhodium and cinchona-based squaramide has first been introduced for asymmetric relay catalysis, enabling a highly enantioselective semipinacol rearrangement/Michael addition cascade.
Related JoVE Video
Cruciferous vegetables, glutathione S-transferase polymorphisms, and the risk of colorectal cancer among Chinese men.
Ann Epidemiol
PUBLISHED: 07-23-2013
Show Abstract
Hide Abstract
To assess the associations between cruciferous vegetable (CV) intake, GST gene polymorphisms, and colorectal cancer (CRC) in a population of Chinese men.
Related JoVE Video
Fruit and vegetable intake and risk of CHD: results from prospective cohort studies of Chinese adults in Shanghai.
Br. J. Nutr.
PUBLISHED: 07-19-2013
Show Abstract
Hide Abstract
The protective effects of fruits and vegetables against CHD have been suggested by many epidemiological studies among Western populations. However, prospective data are lacking for Asian populations. In the present study, we examined the associations of fruit and vegetable intake with CHD incidence among 67 211 women (aged 40-70 years) and 55 474 men (aged 40-74 years) living in Shanghai, China. Food intake was assessed using validated FFQ through in-person interviews. Coronary events (non-fatal myocardial infarction or fatal CHD) were identified by biennial home visits and further confirmed by medical record review. During a mean follow-up period of 9·8 and 5·4 years, 148 events in women and 217 events in men were documented and verified. After adjustment for potential confounders, women in the highest quartile of total fruit and vegetable intake (median 814 g/d) had a hazard ratio (HR) of 0·62 (95 % CI 0·38, 1·02) for CHD (P for trend = 0·04) compared with those in the lowest quartile (median 274 g/d). This association was primarily driven by fruits (HR for the highest v. the lowest intake in women: 0·62, 95 % CI 0·37, 1·03). The strength of the association was attenuated after further controlling for history of diabetes or hypertension. For men, no significant association was found for fruit and vegetable intake when analysed either in combination or individually. The present findings suggest that a high consumption of fruits may reduce CHD risk in Chinese women.
Related JoVE Video
AMP-activated protein kinase regulates the vacuolar H+-ATPase via direct phosphorylation of the A subunit (ATP6V1A) in the kidney.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 07-17-2013
Show Abstract
Hide Abstract
The vacuolar H(+)-ATPase (V-ATPase) in intercalated cells contributes to luminal acidification in the kidney collecting duct and nonvolatile acid excretion. We previously showed that the A subunit in the cytoplasmic V1 sector of the V-ATPase (ATP6V1A) is phosphorylated by the metabolic sensor AMP-activated protein kinase (AMPK) in vitro and in kidney cells. Here, we demonstrate that treatment of rabbit isolated, perfused collecting ducts with the AMPK activator 5-aminoimidazole-4-carboxamide-1-?-D-ribofuranoside (AICAR) inhibited V-ATPase-dependent H(+) secretion from intercalated cells after an acid load. We have identified by mass spectrometry that Ser-384 is a major AMPK phosphorylation site in the V-ATPase A subunit, a result confirmed by comparing AMPK-dependent phosphate labeling of wild-type A-subunit (WT-A) with that of a Ser-384-to-Ala A subunit mutant (S384A-A) in vitro and in intact HEK-293 cells. Compared with WT-A-expressing HEK-293 cells, S384A-A-expressing cells exhibited greater steady-state acidification of HCO3(-)-containing media. Moreover, AICAR treatment of clone C rabbit intercalated cells expressing the WT-A subunit reduced V-ATPase-dependent extracellular acidification, an effect that was blocked in cells expressing the phosphorylation-deficient S384A-A mutant. Finally, expression of the S384A-A mutant prevented cytoplasmic redistribution of the V-ATPase by AICAR in clone C cells. In summary, direct phosphorylation of the A subunit at Ser-384 by AMPK represents a novel regulatory mechanism of the V-ATPase in kidney intercalated cells. Regulation of the V-ATPase by AMPK may couple V-ATPase activity to cellular metabolic status with potential relevance to ischemic injury in the kidney and other tissues.
Related JoVE Video
Associations of Tai Chi, walking, and jogging with mortality in Chinese men.
Am. J. Epidemiol.
PUBLISHED: 06-27-2013
Show Abstract
Hide Abstract
Moderate-intensity exercise has attracted considerable attention because of its safety and many health benefits. Tai Chi, a form of mind-body exercise that originated in ancient China, has been gaining popularity. Practicing Tai Chi may improve overall health and well-being; however, to our knowledge, no study has evaluated its relationship with mortality. We assessed the associations of regular exercise and specifically participation in Tai Chi, walking, and jogging with total and cause-specific mortality among 61,477 Chinese men in the Shanghai Mens Health Study (2002-2009). Information on exercise habits was obtained at baseline using a validated physical activity questionnaire. Deaths were ascertained through biennial home visits and linkage with a vital statistics registry. During a mean follow-up of 5.48 years, 2,421 deaths were identified. After adjustment for potential confounders, men who exercised regularly had a hazard ratio for total mortality of 0.80 (95% confidence interval: 0.74, 0.87) compared with men who did not exercise. The corresponding hazard ratios were 0.80 (95% confidence interval: 0.72, 0.89) for practicing Tai Chi, 0.77 (95% confidence interval: 0.69, 0.86) for walking, and 0.73 (95% confidence interval: 0.59, 0.90) for jogging. Similar inverse associations were also found for cancer and cardiovascular mortality. The present study provides the first evidence that, like walking and jogging, practicing Tai Chi is associated with reduced mortality.
Related JoVE Video
Fish intake and risks of total and cause-specific mortality in 2 population-based cohort studies of 134,296 men and women.
Am. J. Epidemiol.
PUBLISHED: 06-20-2013
Show Abstract
Hide Abstract
Despite a proposed protective effect of fish intake on the risk of cardiovascular disease, epidemiologic evidence on fish intake and mortality is inconsistent. We investigated associations of fish intake, assessed through a validated food frequency questionnaire, with risks of total and cause-specific mortality in 2 prospective cohort studies of 134,296 Chinese men and women (1997-2009). Vital status and date and cause of death were ascertained through annual linkage to the Shanghai Vital Statistics Registry database and biennial home visits. Cox regression was used to calculate hazard ratios and corresponding 95% confidence intervals. After excluding the first year of observation, the analysis included 3,666 deaths among women and 2,170 deaths among men. Fish intake was inversely associated with risks of total, ischemic stroke, and diabetes mortality; the corresponding hazard ratios for the highest quintiles of intake compared with the lowest were 0.84 (95% confidence interval (CI): 0.76, 0.92), 0.63 (95% CI: 0.41, 0.94), and 0.61 (95% CI: 0.39, 0.95), respectively. No associations with cancer or ischemic heart disease mortality were observed. Further analyses suggested that the inverse associations with total, ischemic stroke, and diabetes mortality were primarily related to consumption of saltwater fish and intake of long-chain n-3 fatty acids. Overall, our findings support the postulated health benefits of fish consumption.
Related JoVE Video
Pd-catalyzed asymmetric allylic alkylation of pyrazol-5-ones with allylic alcohols: the role of the chiral phosphoric acid in C-O bond cleavage and stereocontrol.
J. Am. Chem. Soc.
PUBLISHED: 06-14-2013
Show Abstract
Hide Abstract
The combination of a palladium complex with a chiral phosphoramidite ligand and a chiral phosphoric acid enables the first highly efficient asymmetric allylic alkylation of pyrazol-5-ones with allylic alcohols, affording multiply functionalized heterocyclic products in high yields with excellent enantioselectivities that would be of great potential in the synthesis of pharmaceutically interesting molecules.
Related JoVE Video
Polycyclic aromatic hydrocarbons: determinants of urinary 1-hydroxypyrene glucuronide concentration and risk of colorectal cancer in the Shanghai Womens Health Study.
BMC Cancer
PUBLISHED: 05-29-2013
Show Abstract
Hide Abstract
Associations between polycyclic aromatic hydrocarbons (PAHs) and colorectal cancer have been reported previously but few studies have characterized PAH exposure using biological measurements. We evaluated colorectal cancer risk in relation to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG), a polycyclic aromatic hydrocarbon (PAH) metabolite, and assessed determinants of PAH exposure among controls in the Shanghai Womens Health Study (SWHS).
Related JoVE Video
Dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Womens Health Study.
Int. J. Cancer
PUBLISHED: 05-21-2013
Show Abstract
Hide Abstract
Nitrate and nitrite are precursors of endogenously formed N-nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Womens Health Study, a cohort of 73,118 women ages 40-70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77-item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow-up, we identified 619 colorectal cancer cases (n?=?383, colon; n?=?236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR?=?1.08; 95% CI: 0.73-1.59). However, among women with vitamin C intake below the median (83.9 mg day(-1) ) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR?=?2.45; 95% CI: 1.15-5.18; p trend?=?0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously formed NOCs increases risk of colorectal cancer.
Related JoVE Video
Biomimetic asymmetric 1,3-dioplar cycloaddition: amino acid precursors in biosynthesis serve as latent azomethine ylides.
Org. Lett.
PUBLISHED: 05-16-2013
Show Abstract
Hide Abstract
The first asymmetric catalytic biomimetic three-component 1,3-dipolar cycloaddition of ?-keto esters and benzylamine with electron-deficient olefins, inspired by the transamination of ?-keto acids involving pyridoxal phosphate (PLP)-dependent enzymes in biological systems, giving several families of structurally diverse pyrrolidine derivatives in high yields and excellent enantioselectivities (up to 99% ee) under mild conditions is described.
Related JoVE Video
Fruit and vegetable intake and the risk of colorectal cancer: results from the Shanghai Mens Health Study.
Cancer Causes Control
PUBLISHED: 05-14-2013
Show Abstract
Hide Abstract
The observed associations of fruit and vegetable consumption with the risk of colorectal cancer have been inconsistent. Therefore, we aimed to evaluate the association of fruit and vegetable consumption with the risk of colorectal cancer among Chinese men.
Related JoVE Video
MicroRNA-181a enhances the chemoresistance of human cervical squamous cell carcinoma to cisplatin by targeting PRKCD.
Exp. Cell Res.
PUBLISHED: 05-13-2013
Show Abstract
Hide Abstract
MicroRNAs(miRNAs) are involved in regulating the response of cancer cells to various therapeutic interventions, but their involvement in the chemoresistance of human cervical squamous cell carcinoma is not fully understood. We found miR-181a was significantly up-regulated in specimens from patients with chemoresistant cervical squamous cell carcinoma. In this study, we aimed to clarify the role of miR-181a in regulating the chemoresistance of cervical cancer. Two human cervical squamous cancer cell lines, SiHa and Me180, were used. Enforced expression of miR-181a enhanced chemoresistance to cisplatin in cervical cancer cells through apoptosis reversion. In a nude mouse xenograft model, the overexpression of miR-181a markedly inhibited the therapeutic response to cisplatin. PRKCD, a target gene of miR-181a and a promoter of apoptosis, was negatively regulated by miR-181a. We found that the effect of miR-181a on chemoresistance was mediated by PRKCD. Additionally, silencing of PRKCD yielded an effect similar to that of miR-181a up-regulation and inhibited apoptosis in cervical cancer cells. Our findings suggest that miR-181a may function as an oncogene and induce chemoresistance in cervical squamous cell carcinoma cells at least in part by down-regulating PRKCD, thus may provide a biomarker for predicting chemosensitivity to cisplatin in patients with cervical squamous cancer.
Related JoVE Video
Activation of interleukin-6/signal transducer and activator of transcription 3 by human papillomavirus early proteins 6 induces fibroblast senescence to promote cervical tumourigenesis through autocrine and paracrine pathways in tumour microenvironment.
Eur. J. Cancer
PUBLISHED: 04-26-2013
Show Abstract
Hide Abstract
Although it is reported that interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) is activated by human papillomavirus (HPV) infection in cervical cancer cells, little is known about the role of IL-6/STAT3 in tumour microenvironment during development of the disease. In this study, we found that cancer-associated fibroblasts (CAF) but not normal fibroblasts (NF) secrete high level of IL-6 with activated STAT3 and appear senescent at early passages in culture or in cervical cancer tissues infected with high-risk HPV, and that treatment of NF with recombinant IL-6 or CAF conditioned medium (CM) induces activation of STAT3 and cellular senescence. IL-6 and STAT3 are either upregulated or activated in Siha and Hela cells infected with HPV 16 or 18, but not in C33A and ME180 cells without HPV 16 or 18 infection. Overexpression of HPV early proteins 6 (E6) activates STAT3, increases IL-6 expression and tumour burden in C33A and ME180 cells, while silencing of HPV E6 by specific shRNA reduces STAT3 activation, IL-6 expression, and tumour formation in Siha and HeLa cells, so does silencing of STAT3 by specific shRNA in HeLa and C33A/E6 cells. The tumour growth of cervical cancer cells reconstituted with CAF or NF is largely affected by inhibition of fibroblast senescence with STAT3 inhibitor or with IL-6 antibody treatment. Thus, we have uncovered a mechanism that fibroblast senescence promotes cervical cancer development through high-risk HPV E6-activated IL-6/STAT3 signalling in tumour microenvironment.
Related JoVE Video
COX-2 promotes breast cancer cell radioresistance via p38/MAPK-mediated cellular anti-apoptosis and invasiveness.
Tumour Biol.
PUBLISHED: 04-03-2013
Show Abstract
Hide Abstract
Radioresistance is one of the major barriers to improve the survival rate of breast cancer patients. Cyclooxygenase 2 (COX-2) is usually overexpressed in highly invasive and metastatic breast cancer, which may indicate an association with breast cancer radioresistance. The function role of COX-2 was investigated by using a radioresistant breast cancer cell line MDA-MB-231/RR10 and its parental cell line MDA-MB-231 cells before or after COX-2 was silenced by a specific small hairpin RNA (shRNA). The cell proliferation, migration, invasion, colony formation, and apoptosis were measured by CCK-8, scratch-wound, transwell, clone formation assay, and flow cytometry. Protein and mRNA expression were analyzed by Western blot and quantitative reverse transcriptase-polymerase chain reaction. COX-2 is upregulated in MDA-MB-231/RR10 cells compared with in MDA-MB-231 cells, and silencing of COX-2 expression by shRNA in MDA-MB-231/RR10 cells decreases the expression of Bcl-2 and Bcl-XL, but increases the proapoptotic protein BAK, leading to the increased apoptosis following treatment with ?-irradiation in comparison with those in control cells. Silencing of COX-2 also increases the expression of ?-catenin and E-cadherin, two anti-invasion proteins, resulting in reduced cell migration and invasion tested by transwell chambers and wound-healing assays. Further study demonstrated that COX-2-induced radioresistance is negatively regulated through the phosphorylation of p38 at Tyr182, and that the phosphorylation of p38 induced by TNF-alpha reduces the expression of Bcl-2, BCL-XL, but increases ?-catenin and E-cadherin, leading to the decreased invasiveness of cells. Our data suggest that COX-2, p38, Bcl-2, Bcl-XL, ?-catenin, and E-cadherin may be considered as potential therapeutic targets against radioresistant breast cancer.
Related JoVE Video
Prediagnosis soy food consumption and lung cancer survival in women.
J. Clin. Oncol.
PUBLISHED: 03-25-2013
Show Abstract
Hide Abstract
We recently reported an inverse association between soy food intake and lung cancer risk among nonsmoking women. The effect size for aggressive lung cancers was larger than that observed for other types of lung cancer. Therefore, we hypothesized that soy consumption may favorably affect the overall survival of patients with lung cancer.
Related JoVE Video
Vegetable-based dietary pattern and liver cancer risk: results from the Shanghai womens and mens health studies.
Cancer Sci.
PUBLISHED: 03-20-2013
Show Abstract
Hide Abstract
Although dietary patterns, specific foods, and their constituents have been linked to cancer risk, the role of dietary patterns and specific food groups in liver cancer risk has not been investigated. In the Shanghai Womens Health Study (SWHS) and Shanghai Mens Health Study (SMHS), two cohort studies of 132 837 Chinese women and men, we evaluated the relationship between dietary patterns, food groups, and liver cancer risk. Through in-person interviews, dietary information intake over the preceding year was collected by using a validated food-frequency questionnaire. Cox regression model was used to estimate hazard ratios and 95% confidence intervals with adjustment for potential confounders. During an average follow-up of 10.9 (SWHS) or 5.5 (SMHS) years, 267 incident liver cancer cases were identified after the first 2 years of study enrolment. Three dietary patterns were derived by factor analysis. A vegetable-based dietary pattern was inversely associated with liver cancer; hazard ratios (95% confidence intervals) for the lowest to highest quartiles were: 1.00; 0.98 (0.71-1.35); 0.93 (0.67-1.29); and 0.58 (0.40-0.84); P(trend) = 0.01. The association was stronger among participants with a history of chronic liver disease. Further analyses showed high intakes of celery, mushrooms, allium vegetables, composite vegetables (including asparagus lettuce and garland chrysanthemum), legumes and legume products were associated with reduced liver cancer risk (all P(trend) < 0.05). Fruit- and meat-based dietary patterns were not associated with liver cancer risk. Our study suggests that a vegetable-based dietary pattern is associated with reduced liver cancer risk.
Related JoVE Video
Chiral gold complex-catalyzed hetero-Diels-Alder reaction of diazenes: highly enantioselective and general for dienes.
J. Am. Chem. Soc.
PUBLISHED: 02-25-2013
Show Abstract
Hide Abstract
A chiral gold(I) complex-catalyzed highly regio- and enantioselective azo hetero-Diels-Alder reaction has been developed. The chiral gold(I) complex acting as a Lewis acid exhibits high efficiency in the activation of urea-based diazene dienophiles. Moreover, this chiral gold catalyst also rendered a cascade intramolecular enyne cycloisomerization/asymmetric azo-HDA reaction.
Related JoVE Video
Enantioselective relay catalytic cascade intramolecular hydrosiloxylation and Mukaiyama aldol reaction.
Chemistry
PUBLISHED: 02-22-2013
Show Abstract
Hide Abstract
Cascading chemistry! The first practical relay catalytic cascade intramolecular hydrosiloxylation of arylacetylene and asymmetric Mukaiyama aldol reaction has been established to give synthetically useful products in high yields and with excellent ee (see scheme).
Related JoVE Video
Brønsted acid/rhodium(II) cooperative catalytic asymmetric three-component aldol-type reaction for the synthesis of 3-amino oxindoles.
Chemistry
PUBLISHED: 02-10-2013
Show Abstract
Hide Abstract
Cooperation is key! Chiral Brønsted acid/rhodium(II) cooperative catalysis enabled an enantioselective three-component aldol-type reaction of 3-diazo oxindoles and anilines with glyoxylates to give highly functionalized and structurally diverse 3-amino oxindoles in high stereoselectivity (>20:1 d.r., 99?% ee; see scheme).
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.