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1.  The Recombinant Maize Ribosome-Inactivating Protein Transiently Reduces Viral Load in SHIV89.6 Infected Chinese Rhesus Macaques 
Toxins  2015;7(1):156-169.
Ribosome inactivating proteins (RIPs) inhibit protein synthesis by depurinating the large ribosomal RNA and some are found to possess anti-human immunodeficiency virus (HIV) activity. Maize ribosome inactivating protein (RIP) has an internal inactivation loop which is proteolytically removed for full catalytic activity. Here, we showed that the recombinant active maize RIP protected chimeric simian-human immunodeficiency virus (SHIV) 89.6-infected macaque peripheral blood mononuclear cells from lysis ex vivo and transiently reduced plasma viral load in SHIV89.6-infected rhesus macaque model. No evidence of immune dysregulation and other obvious side-effects was found in the treated macaques. Our work demonstrates the potential development of maize RIP as an anti-HIV agent without impeding systemic immune functions.
doi:10.3390/toxins7010156
PMCID: PMC4303820  PMID: 25606813
maize RIP; anti-HIV; animal model; viral load
2.  Characteristics and clinical outcome of nonsteroidal anti-inflammatory drug-induced acute hepato-nephrotoxicity among Chinese patients 
World Journal of Gastroenterology : WJG  2014;20(38):13956-13965.
AIM: To determine the clinicopathological characteristics of nonsteroidal anti-inflammatory drug (NSAID)-induced acute hepato-nephrotoxicity among Chinese patients.
METHODS: We conducted a retrospective chart review of patients using the International Classification of Diseases, Ninth Revision diagnosis code for acute kidney injury (AKI) (584.5 or 584.9) and for acute liver injury (ALI) (570.0 or 573.3) from January 2004 to December 2013. Medical records were reviewed to confirm the diagnosis of AKI and ALI and to quantify NSAID administration.
RESULTS: Seven of 59 patients (11.8%) were identified with acute hepato-nephrotoxicity induced by NSAIDs. Five patients (71.4%) received over the recommended NSAIDs dose. Compared with NSAIDs-associated mere AKI, the risk factors of NSAIDs-induced acute hepato-nephrotoxicity are age older than 60 years (57.1%), a high prevalence of alcohol use (71.4%) and positive hepatitis B virus (HBV) markers (85.7%). Compared with NSAIDs-associated mere ALI, the risk factors of NSAIDs-induced acute hepato-nephrotoxicity are age older than 60 years (57.1%), increased extracellular volume depletion (71.4%), and renin-angiotensin-aldosterone system (RAAS) inhibitor combined use (57.1%). Acute interstitial nephritis and acute tubulointerstitial disease were apparent in three out of six (42.9%) kidney biopsy patients, respectively. Acute hepatitis was found in four out of six (66.7%) liver biopsy patients. Overall complete recovery occurred in four patients within a mean of 118.25 ± 55.42 d.
CONCLUSION: The injury typically occurred after an overdose of NSAIDs. The risk factors include age older than 60 years, alcohol use, positive HBV markers, extracellular volume depletion and RAAS inhibitor combined use.
doi:10.3748/wjg.v20.i38.13956
PMCID: PMC4194579  PMID: 25320533
Nonsteroidal anti-inflammatory drug; Hepato-nephrotoxicity; Acute interstitial nephritis; Acute hepatitis; Cholestasis
3.  Effective Treatment of Manganese-Induced Occupational Parkinsonism With p-Aminosalicylic Acid: A Case of 17-Year Follow-Up Study 
Objective
Chronic manganese (Mn) intoxication induces syndromes resembling Parkinson disease. The clinical intervention has largely been unsuccessful. We report a 17-year follow-up study of effective treatment of occupational Mn parkinsonism with sodium para-aminosalicylic acid (PAS).
Methods
The patient, female and aged 50 at the time of treatment, was exposed to airborne Mn for 21 years (1963–1984). The patient had palpitations, hand tremor, lower limb myalgia, hypermyotonia, and a distinct festinating gait. She received 6 g PAS per day through an intravenous drip infusion for 4 days and rested for 3 days as one therapeutic course. Fifteen such courses were carried out between March and June 1987.
Results
At the end of PAS treatment, her symptoms were significantly alleviated, and handwriting recovered to normal. Recent follow-up examination at age 67 years (in 2004) showed a general normal presentation in clinical, neurologic, brain magnetic resonance imaging, and handwriting examinations with a minor yet passable gait.
Conclusions
This case study suggests that PAS appears to be an effective drug for treatment of severe chronic Mn poisoning with a promising prognosis.
doi:10.1097/01.jom.0000204114.01893.3e
PMCID: PMC4180660  PMID: 16766929
4.  Regulation of leptin receptor‐expressing neurons in the brainstem by TRPV1 
Physiological Reports  2014;2(9):e12160.
Abstract
The central nervous system plays a critical role in the regulation of feeding behavior and whole‐body metabolism via controlling the autonomic output to the visceral organs. Activity of the parasympathetic neurons in the dorsal motor nucleus of the vagus (DMV) determines the vagal tone and thereby modulates the function of the subdiaphragmatic organs. Leptin is highly involved in the regulation of food intake and alters neuronal excitability of brainstem neurons. Transient receptor potential vanilloid type 1 (TRPV1) has also been shown to increase neurotransmission in the brainstem and we tested the hypothesis that TRPV1 regulates presynaptic neurotransmitter release to leptin receptor‐expressing (LepRbEGFP) DMV neurons. Whole‐cell patch‐clamp recordings were performed to determine the effect of TRPV1 activation on excitatory and inhibitory postsynaptic currents (EPSC, IPSC) of LepRbEGFP neurons in the DMV. Capsaicin, a TRPV1 agonist increased the frequency of miniature EPSCs in 50% of LepRbEGFP neurons without altering the frequency of miniature IPSCs in the DMV. Stomach‐projecting LepRbEGFP neurons were identified in the DMV using the transsynaptic retrograde viral tracer PRV‐614. Activation of TRPV1 increased the frequency of mEPSC in ~50% of stomach‐related LepRbEGFP DMV neurons. These data demonstrate that TRPV1 increases excitatory neurotransmission to a subpopulation of LepRbEGFP DMV neurons via presynaptic mechanisms and suggest a potential interaction between TRPV1 and leptin signaling in the DMV.
e12160
Our data demonstrate that TRPV1 is involved in the regulation of a subpopulation of leptin receptor‐expressing neurons in the dorsal motor nucleus of the vagus via presynaptic mechanisms.
doi:10.14814/phy2.12160
PMCID: PMC4270226  PMID: 25263209
DMV; leptin; patch‐clamp; TRPV1
5.  A modified total arch replacement combined with a stented elephant trunk implantation for acute type A dissection under deep hypothermic circulatory arrest and selective antegrade cerebral perfusion 
Objectives
Since the optimal management of patients with acute aortic dissection is unclear, this study analyzed total arch replacement combined with stented elephant trunk implantation in the treatment of acute type A aortic dissection.
Methods
Between February 2008 and February 2013, 86 consecutive patients admitted to our hospital for acute type A dissection underwent total arch replacement combined with stented elephant trunk implantation under deep hypothermic circulatory arrest. The Bentall, David, and Wheat procedure was performed on 46, 12 and two patients, respectively. Ascending aorta replacement was performed on 26 patients, while two patients in Bentall group and 7 in ascending aorta replacement group underwent coronary artery bypass grafting as a concomitant procedure.
Results
Sixty-nine patients were male and 17 patients were female, with an average age of 45.2 ± 2.3 years. The in-hospital mortality rate was 5.8%. Two patients presented with persisting paraplegia. The cardiopulmonary bypass time was 186.3 ± 45.2 minutes and the myocardium ischemia time was 102.6 ± 28.1 minutes. Selective antegrade cerebral perfusion time was 29.4 ± 10.3 minutes. Low-body circulatory arrest time was 18.5 ± 8.4 minutes. Mechanical ventilation time was 80.7 ± 11.3 hours. ICU and hospital stays were 5.3 ± 4.8 and 16.8 ± 5.5 days, respectively. Seven patients underwent reoperation for bleeding. During a mean follow-up of 28.5 months, two patients died and 2 patients were lost to follow-up. Obliteration of the false lumen around the stented graft and at the diaphragmatic level occurred in 97.1% (68 of 70) and 70% (49 of 70) of the patients.
Conclusions
Modified total arch replacement combined with stented elephant trunk implantation using selective antegrade cerebral perfusion is a safe and effective alternative for patients with acute type A dissection and produces satisfactory clinical outcomes in our center.
doi:10.1186/s13019-014-0140-6
PMCID: PMC4203861  PMID: 25174987
Dissection; Aortic arch surgery; Total arch replacement; Aortic surgery; Surgical therapy
6.  Trauma-associated Human Neutrophil Alterations Revealed by Comparative Proteomics Profiling 
Proteomics. Clinical applications  2013;7(0):10.1002/prca.201200109.
PURPOSE
Polymorphonuclear neutrophils (PMNs) play an important role in mediating the innate immune response after severe traumatic injury; however, the cellular proteome response to traumatic condition is still largely unknown.
EXPERIMENTAL DESIGN
We applied 2D-LC-MS/MS based shotgun proteomics to perform comparative proteome profiling of human PMNs from severe trauma patients and healthy controls.
RESULTS
A total of 197 out of ~2500 proteins (being identified with at least two peptides) were observed with significant abundance changes following the injury. The proteomics data were further compared with transcriptomics data for the same genes obtained from an independent patient cohort. The comparison showed that the protein abundance changes for the majority of proteins were consistent with the mRNA abundance changes in terms of directions of changes. Moreover, increased protein secretion was suggested as one of the mechanisms contributing to the observed discrepancy between protein and mRNA abundance changes. Functional analyses of the altered proteins showed that many of these proteins were involved in immune response, protein biosynthesis, protein transport, NRF2-mediated oxidative stress response, the ubiquitin-proteasome system, and apoptosis pathways.
CONCLUSIONS AND CLINICAL RELEVANCE
Our data suggest increased neutrophil activation and inhibited neutrophil apoptosis in response to trauma. The study not only reveals an overall picture of functional neutrophil response to trauma at the proteome level, but also provides a rich proteomics data resource of trauma-associated changes in the neutrophil that will be valuable for further studies of the functions of individual proteins in PMNs.
doi:10.1002/prca.201200109
PMCID: PMC3737403  PMID: 23589343
human neutrophil; LC-MS/MS; Proteomics; Trauma; Genomics
7.  Significance of Image Guidance to Clinical Outcomes for Localized Prostate Cancer 
BioMed Research International  2014;2014:860639.
Purpose. To compare toxicity profiles and biochemical tumor control outcomes between patients treated with image-guided intensity-modulated radiotherapy (IG-IMRT) and non-IGRT intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods. Between 2009 and 2012, 65 patients with localized prostate cancer were treated with IG-IMRT. This group of patients was retrospectively compared with a similar cohort of 62 patients who were treated between 2004 and 2009 with IMRT to the same dose without image guidance. Results. The median follow-up time was 4.8 years. The rectal volume receiving ≥40 and ≥70 Gy was significantly lower in the IG-IMRT group. Grade 2 and higher acute and late GI and GU toxicity rates were lower in IG-IMRT group, but there was no statistical difference. No significant improvement in biochemical control at 5 years was observed in two groups. In a Cox regression analysis identifying predictors for PSA relapse-free survival, only preradiotherapy PSA was significantly associated with biochemical control; IG-IMRT was not a statistically significant indicator. Conclusions. The use of image guidance in the radiation of prostate cancer at our institute did not show significant reduction in the rates of GI and GU toxicity and did not improve the biochemical control compared with IMRT.
doi:10.1155/2014/860639
PMCID: PMC4119732  PMID: 25110701
8.  Coding SNPs as intrinsic markers for sample tracking in large-scale transcriptome studies 
BioTechniques  2012;52(6):386-388.
Large-scale transcriptome profiling in clinical studies often involves assaying multiple samples of a patient to monitor disease progression, treatment effect, and host response in multiple tissues. Such profiling is prone to human error, which often results in mislabeled samples. Here, we present a method to detect mislabeled sample outliers using coding single nucleotide polymorphisms (cSNPs) specifically designed on the microarray and demonstrate that the mislabeled samples can be efficiently identified by either simple clustering of allele-specific expression scores or Mahalanobis distance-based outlier detection method. Based on our results, we recommend the incorporation of cSNPs into future transcriptome array designs as intrinsic markers for sample tracking.
doi:10.2144/0000113879
PMCID: PMC4090115  PMID: 22668418
microarray; transcriptome profiling; coding SNP; outlier detection; sample tracking
9.  Maternal protein restriction induces alterations in hepatic tumor necrosis factor-α/CYP7A1 signaling and disorders regulation of cholesterol metabolism in the adult rat offspring 
It is well recognized that adverse events in utero impair fetal development and lead to the development of obesity and metabolic syndrome in adulthood. To investigate the mechanisms linking impaired fetal growth to increased cholesterol, an important clinical risk factor characterizing the metabolic syndrome and cardiovascular disease, we examined the impact of maternal undernutrition on tumor necrosis factor-α (TNF-α)/c-jun N-terminal kinase (JNK) signaling pathway and the cholesterol 7α-hydroxylase (CYP7A1) expression in the livers of the offspring with a protein restriction model. The male offspring with intrauterine growth restriction (IUGR) caused by the isocaloric low-protein diet showed decreased liver weight at birth and augmented circulation and hepatic cholesterol levels at 40 weeks of age. Maternal undernutrition significantly upregulated cytokine TNF-α expression and JNK phospholytion levels in the livers from fetal age to adulthood. Elevated JNK phospholytion could be linked to downregulated hepatocyte nuclear factor-4α and CYP7A1 expression, subsequently led to higher hepatic cholesterol. This work demonstrated that intrauterine malnutrition-induced IUGR might result in intrinsic disorder in hepatic TNF-α/CYP7A1 signaling, and contribute to the development of hypercholesterolemia in later life.
doi:10.3164/jcbn.13-100
PMCID: PMC4078062  PMID: 25120278
perinatal nutrition; TNF-α; JNK; CYP7A1; cholesterol
10.  Folate Intake and the Risk of Breast Cancer: A Dose-Response Meta-Analysis of Prospective Studies 
PLoS ONE  2014;9(6):e100044.
Background
Previous observational studies regarding the existence of an association between folate intake and the risk of breast cancer have been inconsistent. This study aimed to summarize the evidence regarding this relationship using a dose-response meta-analytic approach.
Methodology and Principal Findings
We performed electronic searches of the PubMed, EmBase, and Cochrane Library databases to identify studies published through June 2013. Only prospective observational studies that reported breast cancer effect estimates with 95% confidence intervals (CIs) for more than 2 folate intake categories were included. We excluded traditional case-control studies because of possible bias from various confounding factors. Overall, we included 14 prospective studies that reported data on 677,858 individuals. Folate intake had little effect on the breast cancer risk (relative risk (RR) for highest versus lowest category = 0.97; 95% CI, 0.90–1.05; P = 0.451). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of breast cancer (RR = 0.99; 95% CI, 0.98–1.01; P = 0.361). Furthermore, we used restricted cubic splines to evaluate the nonlinear relationship between folate intake and the risk of breast cancer, and discovered a potential J-shaped correlation between folate intake and breast cancer risk (P = 0.007) and revealed that a daily folate intake of 200–320 µg was associated with a lower breast cancer risk; however, the breast cancer risk increased significantly with a daily folate intake >400 µg.
Conclusion/Significance
Our study revealed that folate intake had little or no effect on the risk of breast cancer; moreover, a dose-response meta-analysis suggested a J-shaped association between folate intake and breast cancer.
doi:10.1371/journal.pone.0100044
PMCID: PMC4059748  PMID: 24932496
11.  Polyunsaturated Fatty Acid Intake and Risk of Lung Cancer: A Meta-Analysis of Prospective Studies 
PLoS ONE  2014;9(6):e99637.
Background
Studies have reported inconsistent results for the existence of an association between polyunsaturated fatty acid (PUFA) intake and risk of lung cancer. The purpose of this study is to summarize the evidence regarding this relationship using a dose response meta-analytic approach.
Methodology and Principal Findings
We searched the PubMed, EmBase, and Cochrane Library electronic databases for related articles published through July 2013. Only prospective studies that reported effect estimates with 95% confidence intervals (CIs) of lung cancer incidence for greater than 2 categories of PUFA intake were included. We did random-effects meta-analyses of study-specific incremental estimates to determine the risk of lung cancer associated with a 5 g per day increase in PUFA intake. Overall, we included 8 prospective cohort studies reporting data on 1,268,442 individuals. High PUFA intake had little or no effect on lung cancer risk (risk ratio [RR], 0.91; 95% CI, 0.78–1.06; P = 0.230). Furthermore, the dose-response meta-analysis also suggested that a 5 g per day increase in PUFA has no significant effect on the risk of lung cancer (RR, 0.98; 95%CI: 0.96–1.01; P = 0.142). Finally, the findings of dose response curve suggested that PUFA intake of up to 15 g/d seemed to increase the risk of lung cancer. Furthermore, PUFA intake greater than 15 g/d was associated with a small beneficial effect and borderline statistical significance. Subgroup analyses for 5 g per day increment in PUFA indicated that the protective effect of PUFA was more evident in women (RR, 0.94; 95% CI, 0.87–1.01; P = 0.095) than in men (RR, 1.00; 95% CI, 0.98–1.02; P = 0.784).
Conclusion/Significance
Our study indicated that PUFA intake had little or no effect on lung cancer risk. PUFA intake might play an important role in lung cancer prevention in women.
doi:10.1371/journal.pone.0099637
PMCID: PMC4055702  PMID: 24925369
12.  Platycodin D from Platycodonis Radix enhances the anti-proliferative effects of doxorubicin on breast cancer MCF-7 and MDA-MB-231 cells 
Chinese Medicine  2014;9:16.
Background
It has been demonstrated that platycodin D (PD) exhibits anti-cancer activities. This study aims to investigate the anti-proliferative effects of the combination of PD and doxorubicin (DOX) on human breast cancer cells (MCF-7 and MDA-MB-231 cells).
Methods
The anti-proliferative effects of different dosages of PD, DOX, and PD + DOX on MCF-7 and MDA-MB-231 cells were determined by the MTT assay. The 10 μM PD, 5 μM DOX, and 10 μM PD + 5 μM DOX induced-protein expression of apoptosis-related molecules on MCF-7 and MDA-MB-231 cells were detected by western blot. The 10 μM PD, 5 μM DOX and 10 μM PD + 5 μM DOX-induced mitochondrial membrane potential changes on MCF-7 and MDA-MB-231 cells were stained with JC-1 before visual determination. The intracellular accumulations of DOX, induced by 10 μM PD, 5 μM DOX and 10 μM PD + 5 μM DOX, were detected by flow cytometry.
Results
PD enhanced anti-cancer activities of DOX were observed in both MCF-7 and MDA-MB-231 cell lines. Compared with mono treatment, the combined treatment increased the protein expression of cleaved poly (ADP-ribose) polymerase and decreased the mitochondrial membrane potential. The combined treatment with PD did not obviously increase the accumulation of DOX in MCF-7 cells (1.66 ± 0.13 in DOX-treated group, and 1.69 ± 0.06 in PD + DOX-treated group, P = 0.76), but it significantly increased the accumulation of DOX in MDA-MB-231 cells (1.76 ± 0.17 in DOX-treated group, 2.09 ± 0.02 in PD + DOX-treated group, P = 0.027).
Conclusion
The combined treatment of DOX and PD exhibited stronger anti-proliferative effects on MCF-7 and MDA-MB-231 cells than DOX and PD treatment did.
doi:10.1186/1749-8546-9-16
PMCID: PMC4075934  PMID: 24982689
13.  The effect of almond consumption on elements of endurance exercise performance in trained athletes 
Background
Almonds are a healthy tree nut food with high nutrient density. Their consumption has been shown to ameliorate oxidative stress, inflammation, etc. The objective of the study was to examine the effect of almonds on elements of endurance exercise performance in trained athletes.
Methods
A 10-week crossover, placebo controlled study was conducted. Eight trained male cyclists and two triathletes were randomly assigned to consume 75 g/d whole almonds (ALM) or isocaloric cookies (COK) with equal subject number. They consumed the assigned food for 4 wks and then the alternate food for another 4 wks. They underwent 3 performance tests including 125-min steady status exercise (SS) and 20-min time trial (TT) on an indoor stationary trainer at the start of the study (BL) and at the end of each intervention phase. Venous blood was collected in the morning prior to the performance test for biochemical measurements and finger blood during the test for glucose determination. Carbohydrate and fat oxidation, energy expenditure, and oxygen use were calculated using respiratory gas analysis.
Results
ALM increased cycling distance during TT by 1.7 km as compared BL (21.9 vs. 20.2 km, P = 0.053) and COK increased 0.6 km (20.8 vs. 20.2 km, P > 0.05). ALM, but not COK, led to higher CHO and lower fat oxidation and less oxygen consumption during TT than BL (P < 0.05), whereas there was no significant difference in heart rate among BL, ALM and COK. ALM maintained higher blood glucose level after TT than COK (P < 0.05). ALM had higher vitamin E and haemoglobin and lower serum free fatty acid (P < 0.05), slightly elevated serum arginine and nitric oxide and plasma insulin (P > 0.05) than BL, and a higher total antioxidant capacity than COK (P < 0.05).
Conclusions
Whole almonds improved cycling distance and the elements related to endurance performance more than isocaloric cookies in trained athletes as some nutrients in almonds may contribute to CHO reservation and utilization and effective oxygen utilization. The results suggest that almonds can be incorporated into diets of those who undertake exercise training for performance improvement.
doi:10.1186/1550-2783-11-18
PMCID: PMC4031978  PMID: 24860277
Almonds; Exercise performance; Substrate oxidation; Antioxidant defense capacity
14.  Developmental Toxicity of Diclofenac and Elucidation of Gene Regulation in zebrafish (Danio rerio) 
Scientific Reports  2014;4:4841.
Environmental pollution by emerging contaminants, e.g. pharmaceuticals, has become a matter of widespread concern in recent years. We investigated the membrane transport of diclofenac and its toxic effects on gene expression and the development of zebrafish embryos. The association of diclofenac with the embryos conformed to the general partition model at low concentration, the partition coefficient being 0.0033 ml per embryo. At high concentration, the interaction fitted the Freundlich model. Most of the diclofenac remained in the extracellular aqueous solution with less than 5% interacting with the embryo, about half of which was adsorbed on the membranes while the rest entered the cytoplasm. Concentrations of diclofenac over 10.13 μM were lethal to all the embryos, while 3.78 μM diclofenac was teratogenic. The development abnormalities at 4 day post treatment (dpt) include shorter body length, smaller eye, pericardial and body edema, lack of liver, intestine and circulation, muscle degeneration, and abnormal pigmentation. The portion of the diclofenac transferred into the embryo altered the expression of certain genes, e.g. down-regulation of Wnt3a and Gata4 and up-regulation of Wnt8a. The alteration of expression of such genes or the regulation of downstream genes could cause defects in the cardiovascular and nervous systems.
doi:10.1038/srep04841
PMCID: PMC4007093  PMID: 24788080
15.  Hepatoprotective effect of Cichorium intybus L., a traditional Uighur medicine, against carbon tetrachloride-induced hepatic fibrosis in rats 
AIM: To investigate the hepatoprotective effect of a Cichorium intybus L. extract (CIE) on CCl4-induced hepatic fibrosis in rats.
METHODS: Seventy-two male Wistar albino rats were randomly divided into six groups of twelve rats each. The normal control group was allowed free access to food and water. Liver injury was performed in the remaining five groups with an i.p. injection of a 1.0 mL/kg CCl4 and olive oil (2:3 v/v) mixture, twice weekly for 8 weeks. All rats, with the exception of the injury model group, were intragastrically (i.g.,) administered quantum satis (q.s.) dosages [CIE group: 6, 18, and 54 mg/kg, respectively; Fu Fang Bie Jia Ruan Gan Pian (FFBJRGP) group: 780 mg/kg]. The oral administration of different drugs was performed on the day before CCl4 administration and subsequently once per day for 8 wk. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), hydroxyproline (Hyp), and glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) in the rat livers were measured. Histopathological changes in the liver were assessed for each group using HE staining and a Masson Trichrome examination. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) was examined by immunohistochemical analysis.
RESULTS: CIE at oral doses of 6, 18, and 54 g/kg per day showed a significant hepatoprotective effect, especially at a dose of 54 g/kg per day. CIE doses reduced the levels of AST (149.04 ± 34.44, P < 0.01), ALT (100.72 ± 27.19, P < 0.01), HA (548.50 ± 65.09, P < 0.01), LN (28.69 ± 3.32, P < 0.01) and Hyp (263.33 ± 75.82, P < 0.01). With regards to hepatoprotective activity, the CIE dose of 54 g/kg per day produced the largest significant effect by increasing GSH (3.11 ± 0.81), SOD (269.98 ± 33.77, P < 0.01) and reducing MDA (2.76 ± 0.51, P < 0.01) levels in the liver. The expressions of TGF-β1 and α-SMA were measured by immunohistology and found to be significantly reduced by CIE in a dose-dependent manner.
CONCLUSION: CIE may effectively protect against CCl4-induced hepatic fibrosis in rats; thus, it is a promising anti-fibrotic therapeutic agent.
doi:10.3748/wjg.v20.i16.4753
PMCID: PMC4000513  PMID: 24782629
Cichorium intybus L. extract; Traditional Uighur medicine; Hepatic fibrosis; Carbon tetrachloride
16.  Differential expressions of BMPR1α, ACTN4α and FABP7 in Hirschsprung disease 
Hirschsprung disease (HSCR) is characterized by the absence of intramural ganglion cells in the nerve plexuses of the distal gut. Recent studies have shown that the bone morphogenetic protein receptor-type IA (BMPR1α), actinin-alpha 4 (ACTN4α) and fatty acid binding protein 7 (FABP7) play important roles in the differentiation and development of neurons. The aganglionic (stenotic) and the ganglionic (normal) colon segment tissues of 60 HSCR patients were collected to investigate the expression pattern of BMPR1α, ACTININ-4α and FABP7 using RT-PCR, quantitative real-time RT-PCR (qRT-PCR) and immunohistochemical staining. The mRNA and protein expressions of BMPR1α and ACTN4α were higher in the stenotic colon segment tissue than those in the normal colon segment tissue. However, the mRNA and protein expressions of FABP7 were lower in the stenotic colon segment tissue than those in the normal colon segment tissue. The study in HSCR patients, findings in mRNA and protein alterations to expecting provide more information to in order to find some clue for the pathomechanism of HSCR disease.
PMCID: PMC4069943  PMID: 24966941
Hirschsprung disease (HSCR); BMPR1α; ACTININ-4α and FABP7; aganglionic (stenotic) colon segment; ganglionic (normal) colon segment
17.  Spatiotemporal expression of Wnt5a during the development of the striated muscle complex in rats with anorectal malformations 
Fecal incontinence and constipation after procedures for anorectal malformations (ARMs) are closely related to the maldevelopment of the striated muscle complex (SMC). Previous studies have demonstrated that myogenic regulatory factors (MRFs) play a significant role in muscle development. Wnt signal pathway is extremely important for MRFs regulation. This study was designed to investigate the spatiotemporal expression pattern of Wnt5a in SMC in ARMs rat embryos. Materials and Methods: Anorectal malformation embryos were induced by ethylene thiourea on embryonic day 10 (E10). Expression levels of protein and mRNA of Wnt5a were confirmed by immunohistochemistry staining, western blot and quantitative real-time PCR (qRT-PCR) between normal rat embryos and embryos with ARMs. Results: Immunostaining revealed that, on embryonic day 17 (E17), the Wnt5a protein was initially expressed in the SMC in normal embryos. With the growth of pregnancy, the positive staining cells gradually increased. The same time-dependent changes of Wnt5a protein were detected in ARMs embryos. Besides, immunostaining showed that Wnt5a had a significant increase in normal embryos compared with ARMs embryos. Similarly, in Western blot and qRT-PCR, the higher expression of Wnt5a protein and mRNA were remarkable in normal embryos during the SMC development, relatively. Conclusion: Our study demonstrated that the downregulation of Wnt5a at the time of SMC development might partly be related to the dysplasia of SMC in ARMs.
PMCID: PMC4069947  PMID: 24966909
Anorectal malformations; Wnt5a; striated muscle complex; expression
18.  Association between Folate Intake and the Risk of Lung Cancer: A Dose-Response Meta-Analysis of Prospective Studies 
PLoS ONE  2014;9(4):e93465.
Background
Studies have reported inconsistent results regarding the existence of an association between folate intake and the risk of lung cancer. The purpose of this study was to summarize the evidence from prospective cohort studies regarding this relationship by using a dose-response meta-analytic approach.
Methodology and Principal Findings
In September 2013, we performed electronic searches in PubMed, Embase, and the Cochrane Library to identify studies examining the effect of folate intake on the incidence of lung cancer. Only prospective cohort studies that reported the effect estimates about the incidence of lung cancer with 95% confidence intervals (CIs) for more than 2 categories of folate intake were included. Overall, we examined 9 cohort studies reporting the data of 566,921 individuals. High folate intake had little effect on the risk of lung cancer (risk ratio [RR], 0.92; 95% CI, 0.84–1.01; P = 0.076). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of lung cancer (RR, 0.99; 95% CI, 0.97–1.01; P = 0.318). Subgroup analysis suggested that the potential protective effect of low folate intake (100–299 µg/day) was more evident in women than men, while the opposite was true of high folate intake (>400 µg/day). Finally, subgroup analyses of a 100 µg/day increment in folate intake indicated that its potential protective effect was more evident in men than in women.
Conclusion/Significance
Our study revealed that folate intake had little or no effect on the risk of lung cancer. Subgroup analyses indicated that an increased folate intake was associated with a reduced risk of lung cancer in men. Furthermore, low folate intake may be a protective factor for women, and high folate intake for men.
doi:10.1371/journal.pone.0093465
PMCID: PMC3979671  PMID: 24713625
19.  WNT3A gene expression is associated with isolated Hirschsprung disease polymorphism and disease status 
WNT3A has been regarded as an activator of the canonical Wnt signaling pathway. It has been found Wnt signaling pathway is closely related with embrionic development and Hirschsprung disease (HSCR). A common haplotype consisting of minor SNPs alleles located in the WNT3A gene has been described as a risk factor for various genetic disorders. However, whether WNT3A contributes to the onset of HSCR has not been identified. The present study aims to detect the interactions of genetic variations in the WNT3A gene and examine the biological expression levels with Hirschsprung disease (HSCR) in the Chinese people. We analyzed WNT3A gene (rs61743220, rs192966556 and rs145882986) variants in the whole blood samples from HSCR patients and normal children (control groups). WNT3A expression was also examined by quantitative real-time PCR (qRT-PCR), western blotting and immunostaining. Consequently, when rs192966556 and rs145882986 alleles of the WNT3A gene lack the SNPs, they are especially associated with a greater risk of HSCR (OR [95% confidence interval] = 1.791, p = 0.001; OR [95% confidence interval] = 1.556, p = 0.003, respectively). The mRNA and protein expressions of WNT3A were higher in the aganglionic colon segment tissues than in the normal ganglionic segments tissues. Immunostaining indicates that the staining of WNT3A was much stronger (brown) in the aganglionic colon segment tissues than that in the normal ganglionic colon segment tissues (colorless or light yellow) in the mucous layer and muscular layer. Although preliminary, these results suggest that WNT3A may play an important role in the pathogenesis of HSCR.
PMCID: PMC4014216  PMID: 24817932
Hirschsprung disease; WNT3A; polymorphism; gene and protein; expression
20.  A parthenogenetic maternal and double paternal contribution to an ovotesticular disorder of sex development 
Background
An ovotesticular disorder of sex development (OT-DSD) was rarely found in human. The mechanism causing such condition is poorly understood. We hereby reported a 11-year-old child with OT-DSD and a karyotype 46,XX/46,XY, a single maternal and double paternal genetic contribution to the patient.
Results
Fluorescence in situ hybridization (FISH), blood grouping, HLA (human leukocyte antigen) haplotyping and a genome-wide scanning of lymphocytes with 398 short tandem repeat microsatellite markers were performed to investigate the origin of the cell lines concerned. ABO typing revealed that two populations of red cells were in the patient, which were group A and group B, both from paternal alleles. HLA haplotyping showed the patient had three haplotypes. Haplotype 1 was inherited from maternity, haplotype 2 and 3 were from paternity. The STR microsatellite analysis showed 25 of the 74 fully informative markers in both parents, three alleles were inherited: one of them was from mother, another two were from father. Seventeen of the thirty-eight paternal markers, the patient inherited two paternal alleles. For 121 informative maternal markers, the patient had a single maternal allele. There were two distinct alleles in locus DXS6810 and DXS1073 on X-chromosome, in which one was from the mother and the other from the father.
Conclusions
The patient was a single maternal and double paternal genetic, which was a type of a parthenogenetic division of a maternal haploid nucleus into two identical nuclei, followed by fertilization by two spermatozoa and fusion of the two zygotes into a single individual at the early embryonic stage. To the best of our knowledge, this is the oldest OT-DSD case of parthenogenetic chimerism. These data provide additional evidence that a parthenogenetic maternal and double paternal contribution causes 46,XX/46,XY OT-DSD.
doi:10.1186/1755-8166-7-16
PMCID: PMC3974030  PMID: 24581244
Ovotesticular disorder of sex development; Parthenogenetic chimera; Molecular genetics
21.  Effect of omega-3 fatty acid supplementation on cancer incidence, non-vascular death, and total mortality: a meta-analysis of randomized controlled trials 
BMC Public Health  2014;14:204.
Background
Omega-3 fatty acids are known to prevent cardiac death. However, previous observational studies have suggested that omega-3 fatty acids are associated with cancer risk in adults. We conducted a meta-analysis based on randomized controlled trials to evaluate the effect of omega-3 fatty acids on the risk of cancer incidence, nonvascular death, and total mortality.
Methods
In February 2013, we performed electronic searches in PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials on cancer incidence, nonvascular death, and total mortality. Relative risk (RR) was used to measure the effect of omega-3 fatty acid supplementation on the risk of cancer incidence, nonvascular death, and total mortality using a random-effect model. The analysis was further stratified by factors that could affect the treatment effects.
Results
Of the 8,746 identified articles, we included 19 trials reporting data on 68,954 individuals. These studies reported 1,039 events of cancer, 2,439 events of nonvascular death, and 7,025 events of total mortality. Omega-3 fatty acid supplementation had no effect on cancer incidence (RR, 1.10; 95% CI: 0.97–1.24; P = 0.12), nonvascular death (RR, 1.00; 95% CI: 0.93–1.08; P = 1.00), or total mortality (RR, 0.95; 95% CI: 0.88–1.03; P = 0.24) when compared to a placebo. Subgroup analysis indicated that omega-3 fatty acid supplementation was associated with a reduction in total mortality risk if the proportion of men in the study population was more than 80%, or participants received alpha-linolenic acid.
Conclusions
Omega-3 fatty acid supplementation does not have an effect on cancer incidence, nonvascular death, or total mortality.
doi:10.1186/1471-2458-14-204
PMCID: PMC3938028  PMID: 24568238
Omega-3 fatty acid; Cancer; Mortality; Meta-analysis
22.  Super sub-wavelength patterns in photon coincidence detection 
Scientific Reports  2014;4:4068.
High-precision measurements implemented with light are desired in all fields of science. However, light acts as a wave, and the Rayleigh criterion in classical optics yields a diffraction limit that prevents obtaining a resolution smaller than the wavelength. Sub-wavelength interference has potential application in lithography because it beats the classical Rayleigh resolution limit. Here, we carefully study second-order correlation theory to establish the physics behind sub-wavelength interference in photon coincidence detection. A Young's double slit experiment with pseudo-thermal light is performed to test the second-order correlation pattern. The results show that when two point detectors are scanned in different ways, super sub-wavelength interference patterns can be obtained. We then provide a theoretical explanation for this surprising result, and demonstrate that this explanation is also suitable for the results found for entangled light. Furthermore, we discuss the limitations of these types of super sub-wavelength interference patterns in quantum lithography.
doi:10.1038/srep04068
PMCID: PMC3925945  PMID: 24531057
23.  Bispectral index in predicting the prognosis of patients with coma in intensive care unit 
BACKGROUND:
The bispectral (BIS) index is a processed electroencephalogram (EEG) parameter with extensive validation and demonstrated clinical utility. The study aimed to investigate the correlation between the BIS index and the prognosis of patients with coma in the ICU.
METHODS:
A total of 208 patients with coma in the ICU were enrolled in this study. According to the BIS value, the patients were divided into four groups: group I, BIS value 0 to 20; group II, BIS value 21 to 40; group III, BIS value 41 to 60; and group IV, BIS value greater than 60. The difference in BIS values with the differences in prognosis of patients with coma was compared between the four groups, and the prognosis of patients with coma was stratified into consciousness, coma, vegetative state, and brain death. Subsequently, the best cut-off score of BIS values calculated for determining the correlation between BIS value and mental state was proposed.
RESULTS:
There are no significant differences in the age and APACHE II scores between the four groups (P>0.05). An inverse correlation was observed between BIS value and mental state (r= –0.749, P=0.00). According to the ROC curve, as BIS value was greater than 42.5, there were higher sensitivity and specificity in conscious-coma patients.
CONCLUSION:
BIS value is correlated with the prognosis of patients with coma in ICU, and BIS value can be a useful marker for estimating the prognosis of comatose patients.
doi:10.5847/wjem.j.issn.1920-8642.2014.01.009
PMCID: PMC4129864  PMID: 25215148
Bispectral index; Coma; Prognosis
24.  Expression analysis of BMP2, BMP5, BMP10 in human colon tissues from Hirschsprung disease patients 
Objective: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor β (TGF β) superfamily. BMP2, BMP5 and BMP10 exert their biological functions by interacting with membrane bound receptors belonging to the serine/threonine kinase family. Hirschsprung disease (HSCR) is characterized by the absence of intramural ganglion cells in the nerve plexuses of the distal gut. However, putative Notch function in enteric nervous system (ENS) development and the etiology of HSCR is unknown. Methods: Aganglionic and ganglionic colon segment tissues of 50 HSCR patients were investigated for the expression pattern of BMP2, BMP5 and BMP10 using real-time RT-PCR, Western blot analysis and immunohistochemical staining. Results: The mRNA levels of BMP2, BMP5 and BMP10 in the stenotic colon segment from HSCR patients were significantly higher than those in the normal ones. Similar increased expressions of them in the stenotic colon segments were detected by Western blotting coupled with densitometry analysis. Lastly, immunohistologicl stain showed significant BMP2, 5 and 10 increases in mucous and muscular layers from stenotic colon segments compared to normal segments. Conclusions: BMP2, BMP5 and BMP10 are elevated in the stenotic colon segment of HSCR, and BMPs signaling plays a pivotal role in the development of HSCR.
PMCID: PMC3925897  PMID: 24551273
Bone morphogenetic proteins (BMPs); Hirschsprung disease (HSCR); enteric nervous system (ENS); stenotic colon; ganglion cell
25.  Glucose buffer is suitable for blood group conversion with α-N acetylgalactosaminidase and α-galactosidase 
Blood Transfusion  2014;12(1):61-66.
Background
It is well known that the buffer plays a key role in the enzymatic reaction involved in blood group conversion. In previous study, we showed that a glycine buffer is suitable for A to O or B to O blood group conversion. In this study, we investigated the use of 5% glucose and other buffers for A to O or B to O blood group conversion by α-N-acetylgalactosaminidase or α-galactosidase.
Materials and methods
We compared the binding ability of α-N-acetylgalactosaminidase/α-galactosidase with red blood cells (RBC) in different reaction buffers, such as normal saline, phosphate-buffered saline (PBS), a disodium hydrogen phosphate-based buffer (PCS), and 5% commercial glucose solution. The doses of enzymes necessary for the A/B to O conversion in different reaction buffers were determined and compared. The enzymes’ ability to bind to RBC was evaluated by western blotting, and routine blood typing and fluorescence activated cell sorting was used to evaluate B/A to O conversion efficiency.
Results
The A to O conversion efficiency in glucose buffer was similar to that in glycine buffer with the same dose (>0.06 mg/mL pRBC). B to O conversion efficiency in glucose buffer was also similar to that in glycine buffer with the same dose (>0.005 mg/mL pRBC). Most enzymes could bind with RBC in glycine or glucose buffer, but few enzymes could bind with RBC in PBS, PCS, or normal saline.
Conclusion
These results indicate that 5% glucose solution provides a suitable condition for enzymolysis, especially for enzymes combining with RBC. Meanwhile, the conversion efficiency of A/B to O was similar in glucose buffer and glycine buffer. Moreover, 5% glucose solution has been used for years in venous transfusion, it is safe for humans and its cost is lower. Our results do, therefore, suggest that 5% glucose solution could become a novel suitable buffer for A/B to O blood group conversion.
doi:10.2450/2013.0023-13
PMCID: PMC3926730  PMID: 24333060
red blood cells; α-galactosidase; α-N-acetylgalactosaminidase; glucose; blood group conversion

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