Effects of dietary supplementation of fish oil plus vitamin D3 on gut microbiota and fecal metabolites, and their correlation with nonalcoholic fatty liver disease risk factors: a randomized controlled trial.

We previously reported that fish oil plus vitamin D3 (FO + D) could ameliorate nonalcoholic fatty liver disease (NAFLD). However, it is unclear whether the beneficial effects of FO + D on NAFLD are associated with gut microbiota and fecal metabolites. In this study, we investigated the effects of dietary supplementation of FO + D on gut microbiota and fecal metabolites and their correlation with NAFLD risk factors. Methods: A total of 61 subjects were randomly divided into three groups: FO + D group (2.34 g day-1 of eicosatetraenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3), FO group (2.34 g day-1 of EPA + DHA), and corn oil (CO) group (1.70 g d-1 linoleic acid). Blood and fecal samples were collected at the baseline and day 90. Gut microbiota were analyzed through 16S rRNA PCR analysis, and fecal co-metabolites were determined via untargeted ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Results: The relative abundance of Eubacterium (p = 0.03) and Lactobacillus (p = 0.05) increased, whereas that of Streptococcus (p = 0.02) and Dialister (p = 0.04) decreased in the FO + D group compared with the CO group. Besides, changes in tetracosahexaenoic acid (THA, C24:6 n-3) (p = 0.03) levels were significantly enhanced, whereas 8,9-DiHETrE levels (p < 0.05) were reduced in the FO + D group compared with the CO group. The changes in 1,25-dihydroxyvitamin D3 levels in the fecal samples were inversely associated with insulin resistance, which was determined using the homeostatic model assessment model (HOMA-IR, r = -0.29, p = 0.02), and changes in 8,9-DiHETrE levels were positively associated with adiponectin levels (r = -0.43, p < 0.05). Conclusion: The present results indicate that the beneficial effects of FO + D on NAFLD may be partially attributed to the impact on gut microbiota and fecal metabolites.

Elevated serum phosphatidylcholine (16:1/22:6) levels promoted by fish oil and vitamin D3 are highly correlated with biomarkers of non-alcoholic fatty liver disease in Chinese subjects.

The aim of the present study was to investigate the relationship between the changes of serum lipid metabolites and the risk factors of non-alcoholic fatty liver disease (NAFLD) after fish oil (FO) or fish oil plus vitamin D (FO + D) intervention in Chinese NAFLD subjects. Seventy-four NAFLD subjects, aged 55.2 ± 15.9 years, were randomized to consume FO + D (n = 23), FO (n = 27) or corn oil (CO, n = 24) capsules for a 3-month intervention. Serum lipid-related metabolites were measured with ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics approach together with multivariate data analysis. The differential metabolites were screened and identified with variable importance in projection (VIP) scores based on orthogonal partial least squares discriminant analysis models. Serum phosphatidylcholine (PC) (16:1/22:6) levels had the highest and second highest VIP scores following FO + D and FO interventions, respectively. Serum PC (16:1/22:6) levels were negatively correlated with circulating alanine transaminase (ALT) (r = -0.268, p = 0.021), triacylglycerol (TAG) (r = -0.236, p = 0.042), interleukin (IL)-1ß (r = -0.401, p < 0.001) and tumor necrosis factor (TNF)-α (r = -0.322, p = 0.005) concentrations, and were positively correlated with high-density lipoprotein cholesterol (HDL-C) (r = 0.272, p = 0.019) concentrations. The present study was the first to report that serum PC (16:1/22:6) levels were highly correlated with ALT, TAG, HDL-C, IL-1ß and TNF-α concentrations, indicating that PC (16:1/22:6) might ameliorate lipid metabolism and inflammation in NAFLD subjects.

Concentrated fish oil ameliorates non-alcoholic fatty liver disease by regulating fibroblast growth factor 21-adiponectin axis.

OBJECTIVES: The fibroblast growth factor 21 (FGF21)-adiponectin axis participates in energy hemostasis and obesity-related syndrome. The present study aimed to investigate whether concentrated fish oil (FO) intervention could alleviate non-alcoholic fatty liver disease (NAFLD) via the regulation of the FGF21-adiponectin axis. METHODS: In a randomized controlled trial, 61 patients with NAFLD, age 55.9 ± 15.6 y, were randomly divided into two groups: FO (3 g/d; n = 30) and corn oil (CO; 3 g/d; n = 31), which served as the control group. RESULTS: After a 3-mo intervention, there were significant net reductions in serum alanine transaminase (-5.4 ± 14.5 U/L vs. -0.25 ± 4.70 U/L; P = 0.001) and triacylglycerol (-0.70 ± 1.10 mmol/L vs. 0.11 ± 1.04 mmol/L; P = 0.018) levels in the FO group compared with the CO group. Furthermore, the mean changes of FGF21 levels (-16.3 ± 20.1 pg/mL vs. 7.2 ± 32.9 pg/mL; P = 0.002) were significantly decreased, but adiponectin levels (1.14 ± 1.53 µg/mL vs. -0.42 ± 2.04 pg/mL; P = 0.011) were significantly increased in the FO group compared with the CO group. In the animal study, the mice fed the high-fat diet demonstrated characteristics of NAFLD. The administration of FO significantly improved high-fat diet-induced hepatic steatosis, insulin resistance, and inflammation compared with the high-fat control group. In addition, FO improved the sensitivity of FGF21, and stimulated the expression levels of adiponectin in the liver. CONCLUSIONS: The present study suggested that FO could potentially ameliorate NAFLD through mediating the FGF21-adiponectin axis.

The effects of fish oil plus vitamin D3 intervention on non-alcoholic fatty liver disease: a randomized controlled trial.

PURPOSE: The present study aimed to investigate fish oil plus vitamin D3 (FO + D) supplementation on biomarkers of non-alcoholic fatty liver disease (NAFLD). METHODS: In a 3-month randomized controlled trial, 111 subjects with NAFLD, aged 56.0 ± 15.9 y, were randomized into FO + D group (n = 37), fish oil group (FO, n = 37) or corn oil group (CO, n = 37). The subjects consumed the following capsules (3 g/day), which provided 2.34 g/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3 (FO + D group), or 2.34 g/day of EPA + DHA (FO group), or 1.70 g/d linoleic acid (CO group). RESULTS: Using multivariable-adjusted general linear model, there were significant net reductions in serum alanine aminotransferase (ALT), and triacylglycerol (TAG) and TNF-α levels in the FO + D and FO groups, compared with the control group (P < 0.05). The supplemental FO + D also showed significant reductions in insulin (- 1.58 ± 2.00 mU/L vs. - 0.63 ± 1.55 mU/L, P = 0.050) and IL-1ß (- 6.92 ± 7.29 ng/L vs. 1.06 ± 5.83 ng/L, P < 0.001) in comparison with control group. Although there were no significant differences between FO + D and FO groups regarding biochemical parameters, supplemental FO + D showed decreases in ALT (from 26.2 ± 13.5 U/L to 21.4 ± 9.6 U/L, P = 0.007), aspartate aminotransferase (AST, from 22.5 ± 7.0 U/L to 20.2 ± 4.0 U/L, P = 0.029), HOMA-IR (from 3.69 ± 1.22 to 3.38 ± 1.10, P = 0.047), and TNF-α (from 0.43 ± 0.38 ng/L to 0.25 ± 0.42 ng/L, P < 0.001) levels following the intervention. CONCLUSION: The present study demonstrated that groups supplemented with FO + D and FO had similar beneficial effects on biomarkers of hepatocellular damage and plasma TAG levels in subjects with NAFLD, while in the FO + D group, there were some suggestive additional benefits compared with FO group on insulin levels and inflammation. TRIAL REGISTRATION: ChiCTR1900024866.

N-3 polyunsaturated fatty acids effectively protect against neural tube defects in diabetic mice induced by streptozotocin.

Folate cannot prevent all neural tube defects (NTD), indicating that other pathogeneses still exist except for the folate deficiency. Maternal diabetes mellitus during pregnancy can increase the risk of offspring NTD. Our previous study showed that polyunsaturated fatty acids (PUFA) were lower in the placenta of human NTD cases than in healthy controls, and the supplementation of fish oil (rich in long-chain (LC) n-3 PUFA, mainly C20:5n-3 and C22:6n-3) had a better prevention effect against sodium valproate induced NTD than corn oil (rich in C18:2n-6) and flaxseed oil (rich in C18:3n-3). The aim of the present study was to investigate whether PUFA could prevent diabetes-induced NTD in mice. Streptozotocin (STZ)-induced diabetic pregnant mice were fed with a normal diet (DMC), a diet containing a low dose of fish oil (DMLn-3), a diet containing a high dose of fish oil (DMHn-3) or a diet rich in corn oil (DMn-6). Healthy pregnant mice were fed with a normal diet (HC). Compared with the DMC group, the rate of NTD was significantly lower in the DMHn-3 group (4.44% vs. 12.50%), but not in the DMLn-3 (11.11%) or DMn-6 group (12.03%). The NTD rate in the DMHn-3 group was comparable with that in the HC group (1.33%) (p = 0.246), and lower than that in the DMn-6 group (p = 0.052). The NTD rate in DMLn-3 and DMn-6 groups was significantly higher than that in the HC group. No significant difference was observed in NTD rate between DMLn-3 and DMHn-3 groups, and between DMLn-3 and DMn-6 groups. Compared with the HC group, the DMC group had a significantly lower C22:6n-3 in both serum and embryos. Fish oil supplementation ameliorated neuroepithelial cell apoptosis, and the apoptotic rate was comparable between DMHn-3 and HC groups. Although the apoptotic rate was significantly lower in the DMn-6 group than the DMC group, it was still much higher than that in the HC group. The proteins P53 and Bax in embryos were higher, while the proteins Bcl-2 and Pax3 were lower in the DMC group than in the HC group. The disturbance of Pax3, P53 and Bax induced by diabetes was abolished in DMLn-3, DMHn-3 and DMn-6 groups. Importantly, Bcl-2 in embryos was restored to the normal level only in the DMHn-3 group but not in the DMLn-3 or DMn-6 group. In conclusion, LC n-3 PUFA enriched fish oil has a protective effect against NTD in diabetes induced by STZ through improving neuroepithelial cell apoptosis, and the mechanism may be by increasing the anti-apoptosis protein Bcl-2 independently of Pax3 and P53.

Skeletal muscle mass indexes and nonalcoholic fatty liver disease in Chinese elders.

BACKGROUND AND OBJECTIVES: As an endocrine organ, the mass of skeletal muscle is closely related to human health. The present study aimed to investigate the relationship between regional skeletal muscle and nonalcoholic fatty liver disease (NAFLD) in Chinese elders. METHODS AND STUDY DESIGN: A total of 1,328 participants (579 males and 749 females), aged 65 to 96 years were recruited between March to November 2020 in Qingdao, China. Of these, 400 cases and 400 healthy controls, matched by gender and age (±3 years), were included in the study. Skeletal muscle mass was measured by bioelectrical impedance analysis, and body weight was adopted to standardize skeletal muscle mass to obtain skeletal muscle mass indexes. RESULTS: Inverse associations were observed for trunk muscle mass index (TMI) (OR=0.42; 95% CI: 0.19, 0.93; p for trend=0.083) and leg skeletal muscle mass index (LMI) (OR=0.41; 95% CI: 0.18, 0.97; p for trend=0.012) with NAFLD risk after adjustment for age, body mass index, glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, dietary intakes of energy, carbohydrate, protein and fat, smoking, alcohol drinking, education and physical activity. Dose-response analysis indicated that per standard deviation increment of LMI was associated with 23% (95%CI: 0.63, 0.95) reduction of NAFLD risk. CONCLUSIONS: The present study demonstrates that higher TMI and LMI are associated with a lower NAFLD risk.

Vitamin D and liver cancer risk: A meta-analysis of prospective studies.

BACKGROUND AND OBJECTIVES: The association between circulating vitamin D and liver cancer risk has been controversial on the basis of epidemiological studies. The aim of this study was to quantitatively evaluate this association with prospective studies. METHODS AND STUDY DESIGN: A systematic literature search was implemented in PubMed and Scopus databases up to June 2019. Using a random-effects model, the multivariate-adjusted relative risks (RRs) with corresponding 95% confidence interval (CI) were pooled for the highest versus lowest category. Trend estimation was conducted with a two-stage dose-response meta-analysis. RESULTS: Six independent prospective studies (992 liver cancer events and 60,811 participants) were included for data synthesis. The summary estimate showed that a higher circulating vitamin D was associated with lower risk of liver cancer (Summary RR=0.78; 95% CI: 0.63, 0.95; I2=53.6%, p=0.035). Dose-response analysis indicated that liver cancer was associated with 8% (95% CI: 0.89, 0.95) lower risk with a 10 nmol/L increment of circulating vitamin D concentration. CONCLUSIONS: The present study provides substantial evidence that a higher concentration of circulating vitamin D would have conferred protection against liver cancer.

Dietary intakes of fruits and vegetables and lung cancer risk in participants with different smoking status: a meta-analysis of prospective cohort studies.

BACKGROUND AND OBJECTIVES: The results from epidemiological studies are controversial between vegetable and fruit consumption and lung cancer risk in participants with different smoking status. The present meta-analysis aimed to investigate these associations with prospective cohort studies. Meanwhile, the potential dose-response relationship was evaluated. METHODS AND STUDY DESIGN: Relevant studies were identified with PubMed and Scopus databases up to June 2019. Multivariate-adjusted relative risks for the highest versus the lowest category and 95% confidence intervals were calculated by using a random-effects model. The dose-response relationship was examined by using restricted cubic spline regression model. RESULTS: Eight prospective studies were included for data synthesis. The summary estimates indicated that higher vegetable and fruit intake was significantly associated with lower risk of lung cancer in participants with current smokers (RR: 0.84, 95% CI: 0.73, 0.95; I2=25.2%). No significant association was found in former smokers (RR: 0.97, 95% CI: 0.88, 1.07; I2=15.0%) and never smokers (RR: 0.90, 95% CI: 0.74, 1.11; I2=6.6%). Dose-response analysis showed that 100 g/day increment of vegetable and fruit intake was associated with a 2% reduction in lung cancer risk among current smokers (95% CI: 0.97, 0.99). CONCLUSIONS: The present meta-analysis provides significant evidence of an inverse association between vegetable and fruit intake and lung cancer risk in current smokers.

Effect of Betaine on Reducing Body Fat-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Animal studies have shown the beneficial effect of betaine supplementation on reducing body fat, while the data from human studies are controversial and inconsistent. The objective of the present systematic review was to investigate the effects of betaine intervention on treating obesity in humans and quantitatively evaluate the pooled effects based on randomized controlled trials with a meta-analysis. The PubMed and Scopus databases, and the Cochrane Library, were searched up to September 2019. Weighted mean differences were calculated for net changes in obesity-related indices by using a random-effects model. Publication bias was estimated using Begg's test. Six studies with 195 participants were identified. Betaine supplementation significantly reduced the total body fat mass (-2.53 kg; 95% CI: -3.93, -0.54 kg; I2 = 6.6%, P = 0.36) and body fat percentage (-2.44%; 95% CI: -4.20, -0.68%; I2 = 0.0%, P = 0.44). No changes were observed regarding body weight (-0.29 kg; 95% CI: -1.48, 0.89 kg; I2 = 0.00%, P = 0.99) and body mass index (-0.10 kg/m2; 95% CI: -5.13, 0.31 kg/m2; I2 = 0.00%, P = 0.84). The results suggested that dietary betaine supplementation might be an effective approach for reducing body fat.

The Associations of Fruit and Vegetable Intake with Lung Cancer Risk in Participants with Different Smoking Status: A Meta-Analysis of Prospective Cohort Studies.

The results of epidemiological studies on the relationship between fruit and vegetable intake and lung cancer risk were inconsistent among participants with different smoking status. The purpose of this study was to investigate these relationships in participants with different smoking status with prospective cohort studies. A systematic literature retrieval was conducted using PubMed and Scopus databases up to June 2019. The summary relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were calculated by random-effects model. The nonlinear dose-response analysis was carried out with restricted cubic spline regression model. Publication bias was estimated using Begg's test. Nine independent prospective studies were included for data synthesis. Dietary consumption of fruit was negatively correlated with lung cancer risk among current smokers and former smokers, and the summery RRs were 0.86 (95% CI: 0.78, 0.94) and 0.91 (95% CI: 0.84, 0.99), respectively. Consumption of vegetable was significantly associated with reduced risk of lung cancer for current smokers (summary RR = 87%; 95% CI: 0.78, 0.94), but not for former smokers and never for smokers. Dose-response analysis suggested that risk of lung cancer was reduced by 5% (95% CI: 0.93, 0.97) in current smokers, and reduced by 4% (95% CI: 0.93, 0.98) in former smokers with an increase of 100 grams of fruit intake per day, respectively. Besides, dose-response analysis indicated a 3% reduction in lung cancer risk in current smokers for 100 gram per day increase of vegetable intake (95% CI: 0.96, 1.00). The findings of this study provide strong evidence that higher fruit consumption is negatively associated with the risk of lung cancer among current smokers and former smokers, while vegetable intake is significantly correlated with reducing the risk of lung cancer in current smokers. These findings might have considerable public health significance for the prevention of lung cancer through dietary interventions.

Fruit and vegetable intake and liver cancer risk: a meta-analysis of prospective cohort studies.

The associations of vegetable and fruit intake with liver cancer risk have been inconsistent based on epidemiological studies. The present study aimed to quantitatively evaluate these associations with prospective cohort studies. A systematic literature search was performed with PubMed and Scopus databases up to June 2019. Multivariate-adjusted relative risks (RRs) with a corresponding 95% confidence interval (CI) for the highest versus lowest category were pooled by using a random-effects model. Pre-specified subgroup and univariate meta-regression analyses were performed to identify the sources of heterogeneity. Dose-response analysis was conducted by using the variance weighted least squares regression model. Nine independent prospective cohort studies with 1703 liver cancer events and 1 326 176 participants were included for data synthesis. The summary estimates showed that higher vegetable intake was associated with a 39% (95%CI: 0.50, 0.75) reduction in liver cancer risk, with no significant between-study heterogeneity (P = 0.057). Dose-response analysis indicated that the risk of liver cancer was reduced by 4% (95%CI: 0.97, 0.95; P for trend <0.001) with a 100 gram per day increment of vegetable intake. Subgroup analysis showed that higher intakes of vegetables were associated with a 50% (95%CI: 0.35, 0.72) reduction of liver cancer risk in males, but not in females. However, a non-significant association was found between fruit intake and liver cancer risk. The present study provides strong evidence that higher intakes of vegetables would have beneficial effects on the prevention of liver cancer, especially for males.

Effects of EPA and DHA on blood pressure and inflammatory factors: a meta-analysis of randomized controlled trials.

The present study aimed to clarify whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have differential effects on blood pressure and inflammatory mediators. A systematic literature search was conducted in PubMed and Scopus updated to Apr. 2018. The mean changes in risk factors of chronic diseases were calculated as weighted mean difference (WMD) by using a random-effects model. Twenty randomized controlled trials (RCTs) were included. The summary estimate showed that EPA intervention significantly reduced systolic blood pressure (SBP) (-2.6 mmHg; 95%confident interval (CI): -4.6, -0.5 mmHg), especially in subjects with dyslipidemia (-3.8 mmHg; 95%CI: -6.7, -0.8 mmHg). The pooled effect indicated that supplemental DHA exerted a significant reduction in diastolic blood pressure (DBP) in subjects with dyslipidemia (-3.1 mmHg; 95%CI: -5.9, -0.2 mmHg). Both EPA (-0.56 mg/L; 95%CI: -1.13, 0.00) and DHA (-0.5 mg/L; 95%CI: -1.0, -0.03) significantly reduced the concentrations of C-reactive protein (CRP), respectively, especially in subjects with dyslipidemia and higher baseline CRP concentrations. Given that limited trials have focused on EPA or DHA intervention on concentrations of interleukin (IL)-6 and tumor necrosis factor (TNF)-α, further RCTs should be explored on these inflammatory factors. The present meta-analysis provides substantial evidence that EPA and DHA have independent (blood pressure) and shared (CRP concentration) effects on risk factors of chronic diseases, and high-quality RCTs with multi-center and large simple-size should be performed to confirm the present findings.

Oxidative stress impairs myocyte autophagy, resulting in myocyte hypertrophy.

NEW FINDINGS: What is the central question of this study? Does oxidative stress induce impairment of autophagy that results in myocyte hypertrophy early after pressure overload? What is the main finding and its importance? In cultured myocytes, hydrogen peroxide decreased autophagy and increased hypertrophy, and inhibition of autophagy enhanced myocyte hypertrophy. In rats with early myocardial hypertrophy after pressure overload, myocyte autophagy was progressively decreased. The antioxidant N-acetyl-cysteine or the superoxide dismutase mimic tempol prevented the decrease of myocyte autophagy and attenuated myocyte hypertrophy early after pressure overload. These findings suggest that oxidative stress impairs myocyte autophagy that results in myocyte hypertrophy. ABSTRACT: Insufficient or excessive myocyte autophagy is associated with left ventricular (LV) hypertrophy. Reactive oxygen species mediate myocyte hypertrophy in vitro and pressure overload-induced LV hypertrophy in vivo. In the present study, we tested the hypothesis that oxidative stress induces an impairment of autophagy that results in myocyte hypertrophy. H9C2 cardiomyocytes pretreated with the autophagy inhibitor 3-methyladenine were exposed to 10 and 50 µm hydrogen peroxide (H2 O2 ) for 48 h. Male Sprague-Dawley rats underwent abdominal aortic constriction (AAC) or sham operation. The animals were killed 24, 48 or 72 h after surgery. In a separate group, the AAC and sham-operated rats randomly received the antioxidant N-acetyl-cysteine or the superoxide dismutase mimic tempol for 72 h. In H9C2 cardiomyocytes, H2 O2 decreased the ratio of microtubule-associated protein light chain 3 (LC3) II to LC3 I and increased P62 and phosphorylated ERK (p-ERK) proteins and myocyte surface area. 3-Methyladenine further increased H2 O2 -induced p-ERK expression. In rats after AAC, the heart to body weight ratio was progressively increased, the LC3 II/I ratio was progressively decreased, p62 and p-ERK expression was increased, and expression of Beclin1, Atg5 and Atg12 was decreased. N-Acetyl-cysteine or tempol prevented the decreases in the LC3 II/I ratio and Beclin1 and Atg5 expression and attenuated the increases in LV wall thickness, myocyte diameter and brain natriuretic peptide expression in AAC rats. In conclusion, oxidative stress decreases Beclin1 and Atg5 expression that results in impairment of autophagy, leading to myocyte hypertrophy. These findings suggest that antioxidants or restoration of autophagy might be of value in the prevention of early myocardial hypertrophy after pressure overload.

Short update on docosapentaenoic acid: a bioactive long-chain n-3 fatty acid.

PURPOSE OF REVIEW: Docosapentaenoic acid (DPA) is a long-chain n-3 polyunsaturated fatty acid that is intermediary between eicosapentaenoic acid and docosahexaenoic acid in the n-3 synthesis pathway. DPA is part of our normal diet through fish and lean red meat. In recent years, DPA has received increasing attention as an important bioactive fatty acid in light of its potential beneficial health effects, which include anti-inflammatory actions, antiplatelet aggregation, and improved plasma lipid prolife. This review provides a short summary of the most recent research on DPA. RECENT FINDINGS: In this review, we report on the latest association data as well as data generated from in-vitro and in-vivo studies on DPA and cardiovascular health, mental health, inflammation, and cancer. We also report on the newly identified DPA metabolites and their effects on exacerbation of inflammation in animal models. SUMMARY: Although there is a growing body of evidence supporting DPA's role as an important bioactive fatty acid, there is a need for more 'cause and effect studies', clinical trials and studies which can reveal whether DPA plays separate roles to those identified for eicosapentaenoic acid and docosahexaenoic acid.

Three core techniques in surgery of neuroepithelial tumors in eloquent areas: awake anaesthesia, intraoperative direct electrical stimulation and ultrasonography.

BACKGROUND: The goal of surgery in the treatment of intrinsic cerebral tumors is to resect the maximum tumor volume, and to spare the eloquent areas. However, it is difficult to discover the eloquent areas intraoperatively due to individual anatomo-functional variability both for sensori-motor and language functions. Consequently, the surgery of intrinsic cerebral tumors frequently results in poor extent of resection or permanent postoperative deficits, or both, and remains a difficult problem for neurosurgeons. METHODS: From January 2003 to January 2010, 112 patients with neuroepithelial tumors in/close to the eloquent areas were operated on under awake anesthesia with the intraoperative direct electrical stimulation for functional mapping of the eloquent areas. The extent of the tumors was verified by intraoperative ultrasonography. The maximal resection of the tumors and minimal damage of the eloquent areas were the surgical goal of all patients. RESULTS: Totally 356 cortical sites in 99 patients were detected for motor response by intraoperative direct electrical stimulation, 50 sites in 16 patients for sensory, 72 sites in 48 patients for language. Sixty-six patients (58.9%) achieved total resection, 34 (30.4%) subtotal and 12 (10.7%) partial. Fifty-eight patients (51.8%) had no postoperative deficit, while 37 patients (33.0%) had transitory postoperative paralysis, 26 patients (23.2%) with transitory postoperative language disturbance and 3 patients (2.7%) with permanent neurological deficits. No patient complained of pain recollection following operation. CONCLUSIONS: Awake anesthesia, intraoperative direct electrical stimulation and ultrasonography are three core techniques for the resection of intrinsic cerebral tumors near the eloquent areas. This new concept allows an improvement in the quality of surgery for neuroepithelial tumors in/adjacent to eloquent areas.

Telomeric plasmid induces human cancer cell dysfunction depending on ATM activity.

Telomeres are essential for chromosome stability and the regulation of the replicative life-span of somatic cells. Many studies showed that exogenous telomeric repeats could activate p53 protein. It is not known how cell dysfunction is induced by telomeric plasmids. A covalent closed circular (ccc) double-stranded plasmid containing (TTAGGG)(96) repeats (pRST5) was transiently transfected into the human gastric cancer MGC-803 cells. We first confirmed that the cell viabilities decreased by 27%, cell senescence increased by 62% and G2/M cycle arrested in pRST5 plasmid transfected cells. Compared to control groups, cells transfected with telomeric plasmids showed an ATM-dependent increasing of p53, TRF1, and TRF2 expression. Furthermore, telomere dysfunction-induced foci (TIF) were observed. In conclusion, telomeric plasmids can elicit endogenous telomere dysfunction and induce cell senescence by activating ATM-p53 pathway.