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1.  Stimulated Raman scattering imaging by continuous-wave laser excitation 
Optics letters  2013;38(9):1479-1481.
We demonstrate a low-cost-stimulated Raman scattering (SRS) microscope using continuous-wave (cw) lasers as excitation sources. A dual modulation scheme is used to remove the electronic background. The cw-SRS imaging of lipids in fatty liver is demonstrated by excitation of C─H stretch vibration.
PMCID: PMC3952503  PMID: 23632524
2.  Milk Fat Globule-EGF Factor VIII Ameliorates Liver Injury after Hepatic Ischemia-Reperfusion 
The Journal of surgical research  2012;180(1):e37-e46.
Hepatic ischemia-reperfusion (I/R) injury is a serious clinical complication that may compromise liver function because of extensive hepatocyte loss. Therefore, the development of novel and effective therapies for hepatic I/R is critical for the improvement of patient outcome. It has been previously shown that administration of milk fat globule-EGF factor VIII (MFG-E8), a membrane-associated secretory glycoprotein, exerts significant beneficial effects under acute inflammatory conditions through multiple physiological processes associated with tissue remodeling.
To determine whether administration of recombinant human (rh) MFG-E8 attenuates liver injury in an animal model of hepatic I/R. Male adult rats were subjected to 70% hepatic ischemia for 90 min, followed by reperfusion. At the beginning of reperfusion, rats were treated intravenously with normal saline (Vehicle) or rhMFG-E8 (160 μg/kg) over a period of 30 min. MFG-E8 levels and various measurements were assessed 4 h after reperfusion. In addition, survival study was conducted in MFG-E8−/− and rhMFG-E8-treated wild-type (WT) mice using a total hepatic ischemia model.
Liver and plasma MFG-E8 protein levels were significantly decreased after hepatic I/R. Administration of rhMFG-E8 significantly improved liver injury, suppressed apoptosis, attenuated inflammation and oxidative stress, and down-regulated NF-κB pathway. We also noticed that rhMFG-E8 treatment restored the down-regulated PPARγ expression after hepatic I/R. MFG-E8−/− mice showed deterioration on survival and, in contrast, rhMFG-E8-treated WT mice showed a significant improvement of survival compared with vehicle-treated WT mice.
MFG-E8-mediated multiple physiological events may represent an effective therapeutic option in tissue injury following an episode of hepatic I/R.
PMCID: PMC3401639  PMID: 22487387
MFG-E8; hepatic ischemia-reperfusion; inflammation; apoptosis; NF-κB; PPARγ
3.  MR imaging of the Amide-Proton Transfer effect and the pH-insensitive Nuclear Overhauser Effect at 9.4 T 
The amide proton transfer (APT) effect has emerged as a unique endogenous molecular imaging contrast mechanism with great clinical potentials. However, in vivo quantitative mapping of APT using the conventional asymmetry analysis is difficult due to the confounding Nuclear Overhauser Effect (NOE) and the asymmetry of the magnetization transfer (MT) effect. Here we showed that the asymmetry of MT contrast from immobile macromolecules is highly significant, and the wide spectral separation associated with a high magnetic field of 9.4 T delineates APT and NOE peaks in a Z-spectrum. Therefore, high resolution apparent APT and NOE maps can be obtained from measurements at three offsets. The apparent APT value was greater in gray matter compared to white matter in normal rat brain, and was sensitive to tissue acidosis and correlated well with ADC in the rat focal ischemic brain. In contrast, no ischemia-induced contrast was observed in the apparent NOE map. The concentration-dependence and the pH insensitivity of NOE were confirmed in phantom experiments. Our results demonstrate that in vivo apparent APT and NOE maps can be easily obtained at high magnetic fields, and the pH-insensitive NOE may be a useful indicator of mobile macromolecular contents.
PMCID: PMC3419318  PMID: 22577042
Magnetization Transfer; Chemical Exchange Saturation Transfer; Amide Proton Transfer; Nuclear Overhauser Effect; MTR asymmetry; Ischemia
4.  Cisplatin upregulates MSH2 expression by reducing miR-21 to inhibit A549 cell growth 
miR-21 can act as an oncogene. MSH2 has been reported that it involved in the DNA mismatch repair (MMR) system and overexpression of MSH2 can induce cell apoptosis. We predicted that MSH2-3′-untranslated region (3′-UTR) was targeted by miR-21 using microRNA analysis softwares. To further explore the roles of miR-21 and MSH2 in A549 cells, we constructed pcDNA-GFP-msh-UTR vector (including MSH2-3′-UTR) to transfect A549 cells with miR-21, GFP positive cells were estimated under a fluorescence microscopy and by flow cytometry. We found miR-21 could obviously downregulate the expression of MSH2, which was further proved by western blotting. Moreover, we treated A549 cells with cisplatin and found that cisplatin could inhibit A549 cell growth in vitro and in vivo. We also found that cisplatin could downregulate miR-21 expression, while increase MSH2 expression in A549 cells. Our results demonstrated that cisplatin could upregulate the expression of MSH2 through downregulating miR-21 to inhibit A549 cell proliferation, which provides new gene targets for drug design or cancer therary.
PMCID: PMC3646586  PMID: 23485110
microRNA; Lung cancer; MSH2; Cisplatin; Gene expression
5.  MicroRNA 329 Suppresses Angiogenesis by Targeting CD146 
Molecular and Cellular Biology  2013;33(18):3689-3699.
CD146, an endothelial biomarker, has been shown to be aberrantly upregulated during pathological angiogenesis and functions as a coreceptor for vascular endothelial growth factor receptor 2 (VEGFR-2) to promote disease progression. However, the regulatory mechanisms of CD146 expression during angiogenesis remain unclear. Using a microRNA screening approach, we identified a novel negative regulator of angiogenesis, microRNA 329 (miR-329), that directly targeted CD146 and inhibited CD146-mediated angiogenesis in vitro and in vivo. Endogenous miR-329 expression was downregulated by VEGF and tumor necrosis factor alpha (TNF-α), resulting in the elevation of CD146 in endothelial cells. Upregulation of CD146 facilitated an endothelial response to VEGF-induced SRC kinase family (SKF)/p38 mitogen-activated protein kinase (MAPK)/NF-κB activation and consequently promoted endothelial cell migration and tube formation. Our animal experiments showed that treatment with miR-329 repressed excessive CD146 expression on blood vessels and significantly attenuated neovascularization in a mouse model of pathological angiogenesis. Our findings provide the first evidence that CD146 expression in angiogenesis is regulated by miR-329 and suggest that miR-329 could present a potential therapeutic tool for the treatment of angiogenic diseases.
PMCID: PMC3753872  PMID: 23878390
6.  Uncovering the Rare Variants of DLC1 Isoform 1 and Their Functional Effects in a Chinese Sporadic Congenital Heart Disease Cohort 
PLoS ONE  2014;9(2):e90215.
Congenital heart disease (CHD) is the most common birth defect affecting the structure and function of fetal hearts. Despite decades of extensive studies, the genetic mechanism of sporadic CHD remains obscure. Deleted in liver cancer 1 (DLC1) gene, encoding a GTPase-activating protein, is highly expressed in heart and essential for heart development according to the knowledge of Dlc1-deficient mice. To determine whether DLC1 is a susceptibility gene for sporadic CHD, we sequenced the coding region of DLC1 isoform 1 in 151 sporadic CHD patients and identified 13 non-synonymous rare variants (including 6 private variants) in the case cohort. Importantly, these rare variants (8/13) were enriched in the N-terminal region of the DLC1 isoform 1 protein. Seven of eight amino acids at the N-terminal variant positions were conserved among the primates. Among the 9 rare variants that were predicted as “damaging”, five were located at the N-terminal region. Ensuing in vitro functional assays showed that three private variants (Met360Lys, Glu418Lys and Asp554Val) impaired the ability of DLC1 to inhibit cell migration or altered the subcellular location of the protein compared to wild-type DLC1 isoform 1. These data suggest that DLC1 might act as a CHD-associated gene in addition to its role as a tumor suppressor in cancer.
PMCID: PMC3938602  PMID: 24587289
7.  Anti-VEGF Agents with or without Antimetabolites in Trabeculectomy for Glaucoma: A Meta-Analysis 
PLoS ONE  2014;9(2):e88403.
We aimed to evaluate the intraoperative application of antimetabolites compared with anti-vascular endothelial growth factor (VEGF) agents with or without antimetabolites in trabeculectomy (Trab) for glaucoma.
Relevant studies were selected through extensive search using PubMed, EMBASE, the Cochrane Library, and Web of Science databases in August 2013. The primary efficacy estimate was measured using weighted mean difference of the percentage of intraocular pressure reduction (IOPR%) from baseline to end-point, and the secondary efficacy estimates were odds ratio (OR) and 95% confidence interval (CI) for complete success rate and qualified success rate. ORs were also used to measure the tolerability estimate for adverse events. Meta-analyses of fixed or random effects models were conducted using RevMan software 5.2 to pool the results of the studies included. Heterogeneity was assessed using Chi2 test and the I2 measure.
Nine studies enrolling a total of 349 patients were included. The weighted mean difference of IOPR% from baseline was 7.23 (95% CI: 2.57–11.89) for antimetabolites vs. anti-VEGF agents and 3.96 (95% CI: −4.18–12.10) for antimetabolites vs. anti-VEGF agents plus antimetabolites. The pooled ORs comparing antimetabolites with anti-VEGF agents were 2.37 (95% CI: 0.78, 7.21) for the complete success rate and 1.93 (95% CI: 0.52, 7.16) for qualified success rate. The pooled ORs comparing antimetabolites with anti-VEGF agents plus antimetabolites were 1.43 (95% CI: 0.48, 4.29) for the complete success rate and 2.11 (95% CI: 0.12, 37.72) for qualified success rate. The rates of adverse events did not significantly differ between antimetabolites and anti-VEGF agents, with pooled ORs of 0.86 (0.28–2.69) for bleb leakage, 3.01 (0.45–20.10) for choroidal effusion, 0.96 (0.23–3.98) for flat anterior chamber, and 0.90 (0.12–6.60) for hypotony. Further, the rates of adverse events were similar between antimetabolites and anti-VEGF agents plus antimetabolites, with pooled ORs of 0.40 (0.08–2.00) and 8.00 (0.93–68.59) for bleb leakage and hypotony, respectively.
In comparison with anti-VEGF agents, antimetabolites were more effective in lowering IOP in Trab, while the intraoperative application of these two types of agents did not indicate statistically significant differences in the complete success rate, qualified success rate, or incidence of adverse events.
PMCID: PMC3921170  PMID: 24523890
8.  LSD2/KDM1B and Its Cofactor NPAC/GLYR1 Endow a Structural and Molecular Model for Regulation of H3K4 Demethylation 
Molecular cell  2012;49(3):558-570.
Dynamic regulation of histone methylation represents a fundamental epigenetic mechanism underlying eukaryotic gene regulation, yet little is known about how the catalytic activities of histone demethylases are regulated. Here, we identify and characterize NPAC/GLYR1 as an LSD2/KDM1b-specific cofactor that stimulates H3K4me1 and H3K4me2 demethylation. We determine the crystal structures of LSD2 alone and LSD2 in complex with the NPAC linker region in the absence or presence of histone H3 peptide, at resolutions of 2.9, 2.0, and 2.25 Å, respectively. These crystal structures and further biochemical characterization define a dodecapeptide of NPAC (residues 214–225) as the minimal functional unit for its cofactor activity and provide structural determinants and a molecular mechanism underlying the intrinsic cofactor activity of NPAC in stimulating LSD2-catalyzed H3K4 demethylation. Thus, these findings establish a model for how a cofactor directly regulates histone demethylation and will have a significant impact on our understanding of catalytic-activity-based epigenetic regulation.
PMCID: PMC3625064  PMID: 23260659
9.  Evidence of Gene−Environment Interaction for Two Genes on Chromosome 4 and Environmental Tobacco Smoke in Controlling the Risk of Nonsyndromic Cleft Palate 
PLoS ONE  2014;9(2):e88088.
Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10−6
PMCID: PMC3916361  PMID: 24516586
Traditional Chinese medicine (TCM) is practiced in the Chinese health care system for more than 2,000 years. In recent years, herbal medicines, which are used to treat Alzheimer's disease (AD) in China based on TCM or modern pharmacological theories have attracted considerable attention. In this paper, we discuss etiology and pathogenesis of AD, TCM therapy, and herbal extracts for the treatment of AD. There is evidence to suggest that TCM therapy may offer certain complementary cognitive benefits for the treatment of AD. Chinese herb may have advantages with multiple target regulation compared with the single-target antagonist in view of TCM.
PMCID: PMC3927560  PMID: 24624220
PLoS ONE  2014;9(1):e86360.
Due to language limitations, little is known about the reporting quality of randomized clinical trials (RCTs) on the treatment of coronary heart disease (CHD) with traditional Chinese medicine (TCM) in Chinese Journal of Integrated Traditional and Western Medicine (CJITWM).
In this study, we utilized the CONSORT 2010 statement to understand the reporting quality of RCTs on CHD with TCM from the CJITWM.
The China National Knowledge Infrastructure (CNKI) electronic database was searched for CJITWM RCTs on the treatment of CHD with TCM, published between Janurary 1, 2006 and December 31, 2011. We excluded articles reported as “animal studies,” “topic review,” “diagnostic test,” “editorials,” or “others.” The CONSORT checklist was applied to evaluate the reporting quality of all eligible articles by two independent authors after extensive discussion. Each item was graded as either “yes” or “no” depending on whether the authors had reported it or not.
We identified 21 articles meeting our inclusion criteria. The percentage of 11 of the 37 items was 4.8∼95.2%, 14 of the 37 items were reported in all included articles, while 12 items were not mentioned at all. The average reporting percentage for the “title and abstract” section was 52.4%, for the “introduction” section 100.0%, for the “methods” section 45.4%, for the “results” section 57.1%, for the “discussion” section 79.4%, and for the “other information” section 17.5%.
In general, the reviewed RCTs were not consistent with the CONSORT 2010 statement. Authors should adhere to the CONSORT statement in reporting RCTs; editorial departments may consider the CONSORT statement as a guideline and should instruct authors to write manuscripts, and reviewers to judge them according to CONSORT statutes.
PMCID: PMC3904907  PMID: 24489719
PLoS ONE  2014;9(1):e86295.
H19 RNA has been characterized as an oncogenic long non-coding RNA (lncRNA) in breast and colon cancer. However, the role and function of lncRNA H19 in glioma development remain unclear. In this study, we identified that H19/miR-675 signaling was critical for glioma progression. By analyzing glioma gene expression data sets, we found increased H19 in high grade gliomas. H19 depletion via siRNA inhibited invasion in glioma cells. Further, we found H19 positively correlated with its derivate miR-675 expression and reduction of H19 inhibited miR-675 expression. Bioinformatics and luciferase reporter assays showed that miR-675 modulated Cadherin 13 expression by directly targeting the binding site within the 3′ UTR. Finally, introduction of miR-675 abrogated H19 knockdown-induced cell invasion inhibition in glioma cells. To our knowledge, it is first time to demonstrate that H19 regulates glioma development by deriving miR-675 and provide important clues for understanding the key roles of lncRNA-miRNA functional network in glioma.
PMCID: PMC3900504  PMID: 24466011
Primary mucinous lesions of the urinary system are extremely rare. We describe two cases of primary mucinous lesions of the urothelial tract. One case is of mucinous metaplasia in the bladder of a 40-year-old man presenting with frequent urination, urgency, and gross hematuria. The other case is of mucinous adenocarcinoma in the pelvis of an otherwise healthy 67-year-old man with left nephrolithiasis. The histological images of the two cases demonstrate a spectrum from benign mucinous metaplasia to malignant mucinous adenocarcinoma, and suggest that mucinous metaplasia in urothelial tract may be the precancerous lesion of mucinous adenocarcinoma.
PMCID: PMC3902270  PMID: 24482718
Mucinous metaplasia; urothelium; precancerous lesion
This study examined the hypothesis that cardiomyocyte metabolism is inherently linked to the Ubiquitin Proteasome System. Rat neonatal ventricular cardiomyocytes were pulse-treated with 5 αM lactacystin for 30 min, resulting in 95% loss of proteasome activity, and then maintained in culture for up to 24 h. Pulse-treatment resulted in 36% decrease in cardiomyocyte mitochondrial reductase activity by 8 h which improved to 15% by 24 h. Bax proteins were increased 2.5-fold by 8 h but declined by 16 h. Similar effects were observed for ubiquitinated proteins suggesting recovery of proteasome function. Proteasome activity started to increase by 4 h and was back to baseline by 16 h. Multiple proteasome subunits, including α1, were upregulated with peak 2 to 2.5-fold increased protein levels at 8-16 h post-lactacystin which then declined. Incubating cardiomyocytes with 4 αM morpholino-antisense oligonucleotides to the α1-subunit for up to 24 h post-lactacystin diminished recovery of proteasome activity (45% at 24 h) and prevented the increase in α1 protein levels. Ubiquitinated proteins remained elevated and cardiomyocyte mitochondrial reductase activity was decreased 35% by 16 h. These results show that diminished function of the ubiquitin proteasome system decreases cardiomyocyte metabolism. If proteasome activity recovers, function improves, but preventing recovery diminishes metabolic function supporting the hypothesis that cardiomyocyte metabolism is inherently linked to the ubiquitin proteasome system.
PMCID: PMC3925881  PMID: 24551480
Ubiquitin proteasome system; apoptosis; cardiomyocyte; metabolic function
In this article we give a case report on a PTC patient with pancreatic metastasis. In this case, the patient was admitted to our hospital for recurrence of PTC and occupying pancreatic lesions. We considered that the pancreatic neoplasm may be pancreatic metastasis of PTC but there is no previous experience about therapeutic approaches to this type of metastases. After some discussion the distant metastasis within the pancreas was successfully removed by a laparotomy and postoperative histology confirmed the diagnosis. After that surgery, the patient recovered well and then received total thyroidectomy and cervical lymph node dissection for recurrent thyroid cancer. After recovery he was discharged from hospital without further treatment. Eventually, he died of acute myocardial infarction in January 2010. To conclude, it is widely believed that the surgical operation should be chosen more positively in the management of those patients without multiple organ metastases. Thus on one hand it can serve to make a definite diagnosis, and on the other hand it can help the body get rid of the bulk of the tumor burden to prolong survival time of the patients.
PMCID: PMC3925934  PMID: 24551310
Papillary thyroid carcinoma; pancreatic metastasis
PLoS ONE  2014;9(1):e84296.
An established synchronous solid surface fluorimetry (S-SSF) was utilized for in situ study the photolysis processes of anthracene (An) and pyrene (Py) adsorbed on the leaf surfaces of Kandelia obovata seedlings (Ko) and Aegiceras corniculata (L.) Blanco seedlings (Ac). Experimental results demonstrated that the photolysis of An and Py adsorbed on the leaf surfaces of two mangrove species under the laboratory conditions, followed first-order kinetics with their photolysis rates in the order of Ac>Ko. In addition, with the same amount of substances, the photolysis rate of An adsorbed on the same mangrove leaf surfaces was much faster than the adsorbed Py. In order to investigate further, the photolysis processes of An and Py in water were also studied for comparison. And the photolysis of An and Py in water also followed first-order kinetics. Moreover, for the same initial amount, the photolysis rate of the PAH in water was faster than that adsorbed on the leaf surfaces of two mangrove species. Therefore, photochemical behaviors of PAHs were dependent not only on their molecular structures but also the physical-chemical properties of the substrates on which they are adsorbed.
PMCID: PMC3880285  PMID: 24404158
Shock (Augusta, Ga.)  2013;39(1):3-10.
The Wnt/β-catenin signaling pathway is well characterized in stem cell biology and plays a critical role in liver development, regeneration, and homeostasis. We hypothesized that pharmacological activation of Wnt signaling protects against hepatic ischemia/reperfusion (I/R) injury through its known proliferative and anti-apoptotic properties. Sprague-Dawley rats underwent 70% hepatic ischemia by microvascular clamping of the hilum of the left and median lobes of the liver for 90 min, followed by reperfusion. Wnt agonist (2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine, 5 mg/kg BW) or vehicle (20% DMSO in saline) in 0.5 ml was injected intraperitoneally (i.p.) 1 h prior to ischemia or infused intravenously over 30 min right after ischemia. Blood and tissue samples from the pre-treated groups were collected 24 h after reperfusion, and a survival study was performed. Hepatic expression of β-catenin and its downstream target gene Axin2 were decreased after I/R while Wnt agonist restored their expression to sham levels. Wnt agonist blunted I/R-induced elevations of AST, ALT, and LDH and significantly improved the microarchitecture of the liver. The cell proliferation determined by Ki67 immunostaining significantly increased with Wnt agonist treatment and inflammatory cascades were dampened in Wnt agonist-treated animals, as demonstrated by attenuations in IL-6, myeloperoxdase, iNOS and nitrotyrosine. Wnt agonist also significantly decreased the amount of apoptosis, as evidenced by decreases in both TUNEL staining as well as caspase-3 activity levels. Finally, the 10-day survival rate was increased from 27% in the vehicle group to 73% in the pre-treated Wnt agonist group and 55% in the Wnt agonist post-ischemia treatment group. Thus, we propose that direct Wnt/β-catenin stimulation may represent a novel therapeutic approach in the treatment of hepatic I/R.
PMCID: PMC3526673  PMID: 23143067
Wnt/β-catenin; hepatic ischemia/reperfusion; proliferation; inflammation; nitrosative stress; apoptosis
PLoS ONE  2013;8(12):10.1371/annotation/59cb3bf3-cddd-470c-a94e-14992796f861.
PMCID: PMC3875689
Journal of molecular and cellular cardiology  2009;46(6):10.1016/j.yjmcc.2009.02.015.
Mitochondrial oxidative phosphorylation is the major source of energy in cardiac muscle. In the streptozotocin-induced diabetic (STZ-DM) mice, myocardial oxidative phosphorylation was perturbated and oxidative phosphorylation complex V (ATP synthase) activity was significantly reduced. To determine the independent effects of hyperglycemia and insulin deficiency on the changes of myocardial complex V, we used phlorizin (Ph) to normalize blood glucose in the diabetic mice. Ph treatment did not improve myocardial complex V activity in the STZ-DM mice, whereas insulin treatment normalized myocardial complex V activity in the diabetic mice. Therefore, the reduction of complex V activity was caused by insulin deficiency and not by hyperglycemia in STZ-DM myocardium. Acute insulin stimulation induced phosphorylation of Akt and translocation of Akt to mitochondria in myocardium. Translocation of phospho-Akt to mitochondria was enhanced in the STZ-DM mice and was blunted in the diet-induced diabetic mice. In parallel, insulin activation of complex V was enhanced in the STZ-DM myocardium and suppressed in the diet-induced diabetic myocardium. In vivo inhibition of Akt blocked insulin stimulation of phospho-Akt translocation and blunted activation of complex V. Insulin-activated Akt translocation to mitochondria in cardiac muscle is a novel paradigm that may have important implications on myocardial bioenergetics.
PMCID: PMC3872534  PMID: 19249309
Akt translocation; Mitochondria; Diabetes; Cardiac muscle; Oxidative phosphorylation; Insulin
Journal of molecular and cellular cardiology  2013;59:10.1016/j.yjmcc.2013.02.016.
Insulin can translocate Akt to mitochondria in cardiac muscle. The goals of this study were to define sub-mitochondrial localization of the translocated Akt, to dissect the effects of insulin on Akt isoform translocation, and to determine the direct effect of mitochondrial Akt activation on Complex V activity in normal and diabetic myocardium. The translocated Akt sequentially localized to the mitochondrial intermembrane space, inner membrane, and matrix. To confirm Akt translocation, in vitro import assay showed rapid entry of Akt into mitochondria. Akt isoforms were differentially regulated by insulin stimulation, only Akt1 translocated into mitochondria. In the insulin-resistant Type 2 diabetes model, Akt1 translocation was blunted. Mitochondrial activation of Akt1 increased Complex V activity by 24% in normal myocardium in vivo and restored Complex V activity in diabetic myocardium. Basal mitochondrial Complex V activity was lower by 22% in the Akt1−/− myocardium. Insulin-stimulated Complex V activity was not impaired in the Akt1−/− myocardium, due to compensatory translocation of Akt2 to mitochondria. Akt1 is the primary isoform that relayed insulin signaling to mitochondria and modulated mitochondrial Complex V activity. Activation of mitochondrial Akt1 enhanced ATP production and increased phosphocreatine in cardiac muscle cells. Dysregulation of this signal pathway might impair mitochondrial bioenergetics in diabetic myocardium.
PMCID: PMC3872535  PMID: 23500391
PLoS ONE  2013;8(12):e82310.
The aim of the present study was to evaluate the single and joint associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes in Tianjin, China.
Between June 2009 and May 2011, health care records of 33,973 pregnant women were collected and their children were measured for birth weight and birth length. The independent and joint associations of prepregnancy BMI and GWG based on the Institute of Medicine (IOM) guidelines with the risks of pregnancy and neonatal outcomes were examined by using Logistic Regression.
After adjustment for all confounding factors, maternal prepregnancy BMI was positively associated with risks of gestational diabetes mellitus (GDM), pregnancy-induced hypertension, caesarean delivery, preterm delivery, large-for-gestational age infant (LGA), and macrosomia, and inversely associated with risks of small-for-gestational age infant (SGA) and low birth weight. Maternal excessive GWG was associated with increased risks of pregnancy-induced hypertension, caesarean delivery, LGA, and macrosomia, and decreased risks of preterm delivery, SGA, and low birth weight. Maternal inadequate GWG was associated with increased risks of preterm delivery and SGA, and decreased risks of LGA and macrosomia, compared with maternal adequate GWG. Women with both prepregnancy obesity and excessive GWG had 2.2–5.9 folds higher risks of GDM, pregnancy-induced hypertension, caesarean delivery, LGA, and macrosomia compared with women with normal prepregnancy BMI and adequate GWG.
Maternal prepregnancy obesity and excessive GWG were associated with greater risks of pregnancy-induced hypertension, caesarean delivery, and greater infant size at birth. Health care providers should inform women to start the pregnancy with a BMI in the normal weight category and limit their GWG to the range specified for their prepregnancy BMI.
PMCID: PMC3869661  PMID: 24376527
Experimental cell research  2012;318(16):10.1016/j.yexcr.2012.06.012.
Oxysterol binding protein related protein 1S (ORP1S) is a member of a family of sterol transport proteins. Here we present evidence that ORP1S translocates from the cytoplasm to the nucleus in response to sterol binding. The sterols that best promote nuclear import of ORP1S also activate the liver X receptor (LXR) transcription factors and we show that ORP1S binds to LXRs, promotes binding of LXRs to LXR response elements (LXREs) and specifically enhances LXR-dependent transcription via the ME.1 and ME.2 enhancer elements of the apoE gene. We propose that ORP1S is a cytoplasmic sterol sensor, which transports sterols to the nucleus and promotes LXR-dependent gene transcription through select enhancer elements.
PMCID: PMC3867128  PMID: 22728266
ORP1; ORP1S; oxysterol; LXR; nuclear import; NLS

Results 1-25 (411)