Clinical features and prognostic significance of tumor involved with subventricular zone in pediatric glioblastoma: a 10-year experience in a single hospital.

PURPOSE: Tumors involved with subventricular zone (SVZ) predicted an adverse prognosis had been well proved in adult glioblastoma (GBM). However, we still know less about its impact on children due to the rarity of pediatric glioblastoma (pGBM). We performed this retrospective study to better understand the clinical and prognostic features of pGBM involved with SVZ. METHODS: Fifty-two patients diagnosed with pGBM at our center between January 2011 and January 2021 were selected for review to demonstrate the characteristics of tumor contacting SVZ. Thirty patients who underwent concurrent chemoradiotherapy and adjuvant chemotherapy postoperatively were selected for survival analysis. RESULTS: Of all the 52 patients, 21 were found to contact SVZ and 31 were not. The median PFS and OS in SVZ + patients were 5.2 and 8.9 months, respectively, whereas median PFS and OS were 11.9 and 17.9 months, respectively, in SVZ - patients. Multivariate analysis showed that involvement of SVZ was an independent prognostic factor for OS while focality at diagnosis was an independent prognostic factor for PFS. Tumors contacted with SVZ tend to have larger volumes, lower incidence of epilepsy, and lower total resect rate and they were more likely to originate from midline location. Age at diagnosis; gender; adjuvant therapy; focality at diagnosis; focality at relapse; mutational status of H3K27M, MGMT, IDH1, and IDH2; and expression of P53 and ATRX protein failed to characterize SVZ + patients. CONCLUSION: Involvement of SVZ predicted worse OS in pGBM and it had some distinct clinical features in comparison with those that did not contact with SVZ. Multifocal tumor at diagnosis was related to a shorter PFS. We should make a further step to clarify its molecular features.

Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma.

BACKGROUND: We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma. METHODS: Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo. RESULTS: Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group. CONCLUSION: ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia.

Clinical Features and Prognostic Factors of Pediatric Glioblastoma: Report of 38 Cases.

OBJECTIVE: To better characterize children with glioblastoma, assess outcomes, and identify prognostic factors associated with overall survival and progression-free survival in a relatively large cohort from a single institution. METHODS: For this retrospective review, 38 pediatric patients with a diagnosis of glioblastoma who were treated at The First Affiliated Hospital of Zhengzhou University between January 2015 and January 2020 were selected. Clinical and pathological characteristics, imaging, treatment, and survival variables were compared. RESULTS: There were 24 boys and 14 girls with a median age of 11.5 years (range, 3-18 years). All patients underwent surgery, with gross total resection in 16 and subtotal resection in 22. Of patients, 18 received radiation combined with chemotherapy, 6 received radiation or chemotherapy alone, and 14 did not receive any adjuvant therapy. Contrast-enhanced magnetic resonance imaging of 21 patients showed rim enhancement, while heterogeneous enhancement was shown on imaging of the other 17 patients. Tumors were observed in hemispheric locations in 19 cases and in central locations in the others. Median overall survival was 10.5 months with a median progression-free survival of 6 months. Extent of resection, adjuvant therapy, and original site of tumor were identified as independent predictors for progression-free survival and overall survival on multivariate analysis. There were significant differences in prognosis among different enhancement characteristics; patients with rim-enhancing tumors had a better prognosis. CONCLUSIONS: Pediatric glioblastoma carries a dismal prognosis. Maximum safe resection followed by adjuvant radiation with chemotherapy is considered standard treatment. Better outcomes are associated with hemispheric tumor locations and rim enhancement on magnetic resonance imaging.

Supratentorial Cortical Ependymomas: A Retrospective Series of 13 Cases at a Single Center.

OBJECTIVE: Cortical ependymomas (CEs), supratentorial ependymomas that selectively involve the cerebral cortex, are relatively rare neoplasms that have not been extensively described. The purpose of our study was to identify the clinical features, radiologic characteristics, and treatment of a series of such tumors. METHODS: Thirteen patients with CEs from our hospital were included in this study. Epidemiologic characteristics, clinical features, imaging findings, treatment methods, and clinical outcomes were reviewed retrospectively. RESULTS: The patients consisted of 7 men and 6 women with mean age of 31.1 ± 23.2 years (range, 4-74 years). The most common clinical manifestation was seizure (n = 11; 85%), followed by headache (n = 2; 15%). None of the tumors were incidentally detected. Eight CEs were located in the right hemisphere and 5 in the left side. The 2 most common tumor locations were the frontal (n = 5; 38%) and parietal lobe (n = 5; 38%). All patients underwent surgical resection. Gross total resection was achieved in 12 patients (92%), and subtotal resection was performed in 1 patient (8%). Ten of the 11 patients who presented with seizure are seizure-free after surgery (91% seizure-free rate). According to the World Health Organization classification system, 9 tumors (69%) were Grade II (ependymoma) and 4 (31%) were Grade III (anaplastic ependymoma). The mean follow-up was 52 months (range, 20-88 months). No recurrence was observed in patients with Grade II CEs. Of 4 patients with Grade III CEs, 2 (50%) suffered from tumor recurrence after initial treatment. CONCLUSIONS: CEs are a rare subset of supratentorial ependymomas that selectively involve the cerebral cortex. Most CEs are low grade and present with seizures. Anaplastic CEs show a greater recurrence rate and a relatively poor prognosis. Gross total resection with or without adjuvant radiotherapy is currently the optimal treatment for CEs. CEs seem to have a more favorable prognosis than other supratentorial ependymomas.

Supratentorial extraventricular ependymomas: A retrospective study focused on long-term outcomes and prognostic factors.

OBJECTIVE: Supratentorial extraventricular ependymomas are relatively rare. Long-term outcomes and prognostic factor for this rare tumor have not been well established. The purpose of this study was to demonstrateprogression-freesurvival(PFS),overallsurvival(OS), and prognostic factors of such tumor. PATIENTS AND METHODS: Fifty-five patients with supratentorial extraventricular ependymomas from our hospital were included in this study. Epidemiological characteristics, clinical features, treatment,long-term outcomes, and prognostic factors for PFS and OS were reviewed retrospectively. RESULTS: The patients consisted of 30 males and 25 females with mean age of 30.0 ±â€¯23.6 years (range, 1-74 years). Twenty-nine tumors were located in the right hemisphere, and 26 in the left side. The 2 most common tumor locations were the frontal (n = 19; 35%) and parietal lobe (n = 11; 20%). All patients underwent surgical resection. Gross-total resection (GTR) was achieved in 42 cases (76%) and subtotal resection (STR) was performed in 13 patients (24%). According to the WHO classification system, 38 tumors (69%) were Grade III (anaplastic ependymoma), and 17 (31%) were Grade II (ependymoma). Three-,5-, and 10 year PFS rates were 60%, 49%, and 36%, respectively. Three-,5-, and 10 year OS rates were 79%, 64%, and 49%, respectively. EOR and tumor grade were identified as prognostic factors for PFS and OS on univariate analysis, multivariate analysis, and Kaplan-Meierlog-rank testing. Subtotal resection (STR) predicted a worse PFS (HR = 4.808; 95%, 1.942-11.905; P = .001) and OS (HR = 5.650; 95%, 2.114-15.152; P = .001). WHO Grade III tumors also had worse PFS (HR = 3.922; 95%, 1.429-18.182; P = .012) and OS (HR = 6.329; 95%, 1.328-30.303; P = 0.021). For patients with tumor recurrence, reoperation was significant prognostic factors for OS (HR = 2.091; 95%, 0.939-4.654; p = .000). Age, sex, tumor side, and postoperativeradiotherapy were not prognostic factors for PFS and OS. CONCLUSIONS: Most supratentorial extraventricular ependymomas are WHO grade III tumors. STRandWHO Grade III pathology predicted worse PFS and OS. Gross-total resection remains the optimal treatment for patients with supratentorial extraventricular ependymoma. Reoperation should be considered first in cases of recurrence. The role of postoperative radiotherapy as an adjuvant treatment for supratentorial extraventricular ependymoma needs further investigation.

miR-152 regulated glioma cell proliferation and apoptosis via Runx2 mediated by DNMT1.

BACKGROUND: Aberrant DNA methylation is associated with tumor onset and progression. Study has verified that the DNA methylation of miR-152 was mediated in many tumors, but whether it involved in glioblastomas was still unclear. METHODS: This study enrolled 20 patients with glioma to analyze the expression pattern of miR-152. Real-time PCR and western blot were used to detect the mRNA or protein expression level, respectively. The relationship between miR-152 and runx2 was detected by Luciferase reporter assay. The methylation level of miR-152 was determined by methylation-specific PCR. Cell proliferation and apoptosis were detected by MTT and Annexin-FITC/PI assay. RESULTS: The expression of miR-152 was down-regulated while the expression of DNMT1 was up-regulated in both glioma tissue and cell lines. MiR-152 was hypermethylated and its expression was negatively correlated with DNMT in glioma cell lines. DNMT1 knockdown promoted the expression of miR-152, however, DNMT1 overexpression suppressed the expression of miR-152. MiR-152 overexpression promoted glioma cell apoptosis while miR-152 knockdown promoted cell proliferation. MiR-152 targets Runx2 to regulate its expression, Runx2 overexpression abolished the effects of miR-152 overexpression. CONCLUSION: MiR-152 regulated cell proliferation and apoptosis of glioma mediated by Runx2, while the mechanism of down regulated miR-152 in glioma tissues and cells was its hypermethylation.

Plasma cholesterol-lowering activity of dietary dihydrocholesterol in hypercholesterolemia hamsters.

OBJECTIVE: Cholesterol analogs have been used to treat hypercholesterolemia. The present study was to examine the effect of dihydrocholesterol (DC) on plasma total cholesterol (TC) compared with that of ß-sitosterol (SI) in hamsters fed a high cholesterol diet. METHODS AND RESULTS: Forty-five male hamsters were randomly divided into 6 groups, fed either a non-cholesterol diet (NCD) or one of five high-cholesterol diets without addition of DC and SI (HCD) or with addition of 0.2% DC (DA), 0.3% DC (DB), 0.2% SI (SA), and 0.3% SI (SB), respectively, for 6 weeks. Results showed that DC added into diet at a dose of 0.2% could reduce plasma TC by 21%, comparable to that of SI (19%). At a higher dose of 0.3%, DC reduced plasma TC by 15%, less effective than SI (32%). Both DC and SI could increase the excretion of fecal sterols, however, DC was more effective in increasing the excretion of neutral sterols but it was less effective in increasing the excretion of acidic sterols compared with SI. Results on the incorporation of sterols in micellar solutions clearly demonstrated both DC and SI could displace the cholesterol from micelles with the former being more effective than the latter. CONCLUSION: DC was equally effective in reducing plasma cholesterol as SI at a low dose. Plasma TC-lowering activity of DC was mediated by inhibiting the cholesterol absorption and increasing the fecal sterol excretion.

[Postpartum weight retention in Beijing, Suzhou and Guangzhou women and its associated factors].

OBJECTIVE: To investigate the prevalence of postpartum weight retention (PPWR) in urban Chinese women, and to explore its associated factors. METHODS: Cluster sampling methods were used to select a total of 6 hospitals in Beijing, Guangzhou and Suzhou. A total of 578 women in the 0 - 1 months, 1 - 2 months, 2 - 4 months and 4 - 8 months postpartum participated in this study. Anthropometric indicators of height and weight were measured for each participant. Questionnaire was used to obtain the sociodemographic characteristics. Maternal information of pre-pregnancy weight and gestational weight gain were obtained by medical records. RESULTS: The pre-pregnancy BMI of participants was (20. 8 ± 2. 7), while postpartum BMI was (23. 4 ± 3. 2). PPWR decreased over time, however, 53. 4% of women had PPWR over 5kg at the 4 - 8 months postpartum. 32. 6% of women were overweight or obese at 4 - 8 months postpartum. Women with PPWR >0kg at 4 - 8 months postpartum had a higher gestational weight gain ((16.5 ± 5.5) kg) compared to those with PPWR≤0 kg ((13.0 ±4.7) kg). Women with higher education experience had a higher proportion of weight retention over 0 kg at 4 - 8 month postpartum. CONCLUSION: PPWR is a serious health and nutritional problem in Chinese women, where excess in gestational weight gain is associated with PPWR. To improve the health and lifestyle of perinatal women, a comprehensive health education and health intervention should be explored.

Pre-pregnancy BMI, gestational weight gain and postpartum weight retention: a meta-analysis of observational studies.

OBJECTIVE: To determine the association of gestational weight gain (GWG) or pre-pregnancy BMI with postpartum weight retention (PPWR). DESIGN: Meta-analysis. SETTING: PubMed, Cochrane Controlled Trials Register, EMBASE, Science Citation Index Expanded, Current Contents Connects and Biosis Previews were used to search articles. SUBJECTS: Publications that described the influence of pre-pregnancy BMI or GWG on PPWR. RESULTS: Seventeen studies that satisfied the eligibility criteria were included in the analyses. Women with inadequate and excessive GWG had significantly lower mean PPWR of -2·14 kg (95 % CI -2·43, -1·85 kg) and higher PPWR of 3·21 kg (95 % CI 2·79, 3·62 kg), respectively, than women with adequate GWG. When postpartum time spans were stratified into 1-3 months, 3-6 months, 6-12 months, 12-36 months and ≥15 years, the association between inadequate GWG and PPWR faded over time and became insignificant (-1·42 kg; 95 % CI -3·08, 0·24 kg) after ≥15 years. However, PPWR in women with excess GWG exhibited a U-shaped trend; that is, a decline during the early postpartum time span (year 1) and then an increase in the following period. Meta-analysis of qualitative studies showed a significant relationship between excessive GWG and higher PPWR risk (OR=2·08; 95 % CI 1·60, 2·70). Moreover, meta-analysis of pre-pregnancy BMI on PPWR indicated that mean PPWR decreased with increasing BMI group. CONCLUSIONS: These findings suggest that GWG, rather than pre-pregnancy BMI, determines the shorter- or longer-term PPWR.

Association between gestational weight gain according to prepregnancy body mass index and short postpartum weight retention in postpartum women.

BACKGROUND & AIMS: This study aims to assess the relationship among prepregnancy body mass index, gestational weight gain, and postpartum weight retention, and to clarify the predictors of the amount of weight retained by Chinese women after pregnancy. METHODS: The multistage stratified random sampling was used in the cross-sectional study. RESULTS: The subjects included 1643 women. Mean gestational weight gain was 15.9 kg and mean postpartum weight retention was 5.1 kg. 43.2% of women gained excessive gestational weight gain and 53.3% of women gained 5 kg or more postpartum weight retention. In addition, the proportions of underweight women with inadequate weight gain and overweight women with excessive weight gain were 24.2% and 52.3%, respectively. Logistic regression analysis showed that the adjusted OR of excessive gestational weight gain was 1.74 (95% CI: 1.09-2.79) in overweight women compared with normal weight women. The postpartum weight retention and the proportion of women with postpartum weight retention of 5 kg or more were significantly higher in the excessive gestational weight gain women than in the adequate gestational weight gain women in all three body mass index groups. The adjusted OR of a weight increase of 5 kg or more was at least 1.90 for underweight, normal weight, and overweight women with a gestational weight gain above the recommended amount compared with those with a gestational weight gain within the recommended amount. CONCLUSIONS: Gestational weight gain above the recommended amount increases the risk of postpartum weight retention in all body mass index groups.

Postconditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury involving mitochondrial ATP-dependent potassium channel and mitochondrial permeability transition pore.

OBJECTIVES: Postconditioning with sevoflurane has been shown to protect against focal cerebral ischemia and reperfusion injury. However, the mechanism remains elusive. In this study, we tested the hypothesis that mitochondrial ATP-sensitive potassium (mitoKATP) and mitochondrial permeability transition pore (mPTP) play roles in the neuroprotection of postconditioning with sevoflurane. METHODS: Adult male Sprague-Dawley rats were subjected to MCAO for 90 minutes and then treated with sevoflurane at the beginning of reperfusion. The infarct volume, neurological deficit score, and brain edema were evaluated at 24 hours. Apoptosis were studied by TUNEL. The neuroprotective effect with or without 5-hydroxydecanoate (5-HD), a selective mitoKATP channel blocker or atractyloside (ATR), and an mPTP opener were analyzed. RESULTS: Postconditioning with sevoflurane significantly decreased neurological deficit scores, infarct volume, and brain edema and also reduced apoptotic cells. 5-HD and ATR abolished the neuroprotective effect, respectively. 5-HD or ATR alone had no effect on ischemia and reperfusion injury. DISCUSSION: Our data suggest that mitoKATP and mPTP play crucial roles in the neuroprotection of postconditioning with sevoflurane.

Mineral compositions in breast milk of healthy Chinese lactating women in urban areas and its associated factors.

BACKGROUND: Optimal mineral intakes are important for infant growth and development. However, data on mineral compositions of breast milk in Chinese women are scarce, and most were acquired before 1990. The objectives of this study were three-fold: (1) to investigate the mineral compositions of Chinese healthy mothers' breast milk in different lactation stages; (2) to explore correlations among mineral concentrations in breast milk; and (3) to explore the associated factors affecting mineral compositions in breast milk. METHODS: The inductively coupled plasma mass spectrometry (ICP-MS) was used to analyze mineral concentrations in breast-milk of 444 healthy lactating women from three cities in China. A questionnaire was used to survey socio-demographic characteristics and pregnancy history. Food intakes by lactating women were measured using both food frequency questionnaire and one cycle of 24-hour dietary recall. RESULTS: Mineral compositions of breast milk varied in different regions. Concentrations of most minerals were higher in the first one or two months of lactation, and then decreased with time, except for magnesium and iron. Inter-mineral correlations existed among several minerals. The calcium-to-phosphorus ratio was above 2:1 in each lactation stage. Women with caesarean section had higher concentration of iodine in the transitional milk (349.9 µg/kg) compared to women with natural delivery (237.5 µg/kg, P < 0.001). Dietary mineral intakes, supplements, food intake frequencies in the recent 6 months, maternal age and maternal BMI did not show significant correlations with concentrations of milk minerals (all P > 0.05). CONCLUSIONS: Milk minerals decreased with time, and changed most rapidly in the first one or two months of lactation. Caesarean section might affect the iodine level in transitional milk.

Nutritional status of breast-fed and non-exclusively breast-fed infants from birth to age 5 months in 8 Chinese cities.

This study aimed to assess the nutritional status of infants aged 0 to 5 months by different feeding approaches. A cross-sectional study on infant nutrition was performed in eight cities in China. A total of 622 infants from birth to 2 months of age and 456 infants from 3 months to 5 months of age were included in this study. Mix-fed infants received breast milk and complementary foods from birth to 2 months of age. Approximately 38.2% of mix-fed infants received excessive vitamin A, and 15.6% of infants exceeded the tolerable upper intake levels (ULs) of zinc. For artificially fed infants who received only complementary foods, approximately 20% and 12.5% infants received inadequate dietary vitamin A and zinc intakes, respectively. The vitamin A and zinc intakes of half of the infants exceeded the ULs. Results showed that the usual intake distribution of the infants from 3 months to 5 months of age were similar to that of the infants from birth to 2 months of age. The common vitamin A and zinc intakes were also severely imbalanced. In addition, higher disease prevalence and lower Z scores of length-forage, weight-for-age, and weight-for-length were found in artificially fed infants and mix-fed infants compared with those in breast-fed infants. In conclusion, the usual nutrient intakes were adequate for the majority of Chinese infants, except for an important number of infants at risk for imbalance of vitamin A and zinc intakes.

Breast milk macronutrient composition and the associated factors in urban Chinese mothers.

BACKGROUND: Infancy is a critical period of growth and physiological development, in which breast milk is the best source of nutrients. Compared to western countries, research on breast milk of Chinese population are limited. Thus, it is necessary to measure breast milk energy and macronutrient concentrations of healthy urban Chinese mothers at different lactation stages, to expand the database of milk composition of Chinese population, and to examine whether dietary or other maternal factors can affect the levels of macronutrients in breast milk. METHODS: Breast milk of full expression of one side breast from 436 urban Chinese lactating mothers at 5-11 days, 12-30 days, 31-60 days, 61-120 days, and 121-240 days postpartum was obtained at 9:00 a.m. to 11:00 a.m. Total energy, lactose, protein, and fat contents were measured. 24-hour dietary recall was surveyed, and maternal nutrient intakes were analyzed. RESULTS: Milk composition changed over the course of lactation and large individual variations were documented. The concentrations were 61.3 kcal/dl for total energy, 7.1 g/dl for lactose, 0.9 g/dl for protein, and 3.4 g/dl for fat in mature milk. Stage of lactation was a strong factor affecting milk composition. Minimal evidence was found for associations between maternal current dietary intake and milk macronutrient concentration, consistently with prior research. Maternal body mass index (BMI) was positively associated with milk fat content, to a greater extent than did dietary intake. All other maternal characteristics were not significant for milk composition. CONCLUSION: These findings suggest that milk composition is generally weakly associated with maternal factors except for stage of lactation, and is likely to be more susceptible to long-term maternal nutritional status than short-term dietary fluctuation.

Bitter gourd inhibits the development of obesity-associated fatty liver in C57BL/6 mice fed a high-fat diet.

Bitter gourd (BG) is a popular fruit in Asia with numerous well-known medicinal uses, including as an antidiabetic. In the current study, we aimed to explore the effects of BG on mitochondrial function during the development of obesity-associated fatty liver. C57BL/6 mice were divided into 4 experimental groups: mice fed a normal diet (control; included for reference only), mice fed a high-fat diet (HFD), and mice fed an HFD supplemented with freeze-dried BG powder through daily gavage at doses of 0.5 (HFD+0.5BG) and 5 (HFD+5BG) g/kg, respectively. After 16 wk, mice in the HFD+5BG group showed less body and tissue weight gain and less hyperglycemia and hyperlipidemia compared with those in the HFD group (P < 0.05). In both HFD+0.5BG and HFD+5BG groups, serum interleukin-6 concentration was lower than that in the HFD group (P < 0.02). The serum C-reactive protein concentration was lower in the HFD+5BG group compared with the HFD group (P < 0.04). An analysis of liver tissue revealed lower liver triglyceride and cholesterol concentrations in both HFD+0.5BG and HFD+5BG groups than in the HFD group (P < 0.01). The HFD+5BG group had less activation of the sterol regulatory element binding protein/fatty acid synthase (SREBP-1/FAS) pathway, greater superoxide dismutase activity, and less total protein and mitochondrial protein oxidation than did the HFD group (P < 0.05). Mitochondrial complex I, II, III, and V activity was greater in the HFD+0.5BG group than in the HFD group (P < 0.03). The HFD+5BG group only had greater complex V activity compared with the HFD group (P < 0.05). Mitochondrial dynamics regulators, including dynamin related protein 1 (DRP1) and mitofusin 1 (MFN1), as well as proapoptotic protein expression levels were restored by BG treatment (P < 0.02). Taken together, our results suggest that BG prevents inflammation and oxidative stress, modulates mitochondrial activity, suppresses apoptosis activation, and inhibits lipid accumulation during the development of fatty liver.

Mitochondrial dysfunction in obesity-associated nonalcoholic fatty liver disease: the protective effects of pomegranate with its active component punicalagin.

AIMS: Punicalagin (PU) is one of the major ellagitannins found in the pomegranate (Punica granatum), which is a popular fruit with several health benefits. So far, no studies have evaluated the effects of PU on nonalcoholic fatty liver disease (NAFLD). Our work aims at studying the effect of PU-enriched pomegranate extract (PE) on high fat diet (HFD)-induced NAFLD. RESULTS: PE administration at a dosage of 150 mg/kg/day significantly inhibited HFD-induced hyperlipidemia and hepatic lipid deposition. As major contributors to NAFLD, increased expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukins 1, 4, and 6 as well as augmented oxidative stress in hepatocytes followed by nuclear factor (erythroid-derived-2)-like 2 (Nrf2) activation were normalized through PE supplementation. In addition, PE treatment reduced uncoupling protein 2 (UCP2) expression, restored ATP content, suppressed mitochondrial protein oxidation, and improved mitochondrial complex activity in the liver. In contrast, mitochondrial content was not affected despite increased peroxisomal proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and elevated expression of genes related to mitochondrial beta-oxidation after PE treatment. Finally, PU was identified as the predominant active component of PE with regard to the lowering of triglyceride and cholesterol content in HepG2 cells, and both PU- and PE-protected cells from palmitate induced mitochondrial dysfunction and insulin resistance. INNOVATION: Our work presents the beneficial effects of PE on obesity-associated NAFLD and multiple risk factors. PU was proposed to be the major active component. CONCLUSIONS: By promoting mitochondrial function, eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of NAFLD.

Effect of probiotic fermented milk on blood pressure: a meta-analysis of randomised controlled trials.

Previous studies have suggested that probiotic fermented milk may possess blood pressure (BP)-lowering properties. In the present study, we aimed to systematically examine the effect of probiotic fermented milk on BP by conducting a meta-analysis of randomised controlled trials. PubMed, Cochrane library and the ClinicalTrials.gov databases were searched up to March 2012 to identify eligible studies.The reference lists of the obtained articles were also reviewed. Either a fixed-effects or a random-effects model was used to calculate the combined treatment effect. Meta-analysis of fourteen randomised placebo-controlled trials involving 702 participants showed that probiotic fermented milk, compared with placebo, produced a significant reduction of 3·10 mmHg (95% CI 24·64, 21·56) in systolic BP and 1·09 mmHg (95% CI 22·11, 20·06) in diastolic BP. Subgroup analyses suggested a slightly greater effect on systolic BP in hypertensive participants than in normotensive ones (23·98 v. 22·09 mmHg). Analysis of trials conducted in Japan showed a greater reduction than those conducted in European countries for both systolic BP (26·12 v. 22·08 mmHg) and diastolic BP (23·45 v. 20·52 mmHg). Some evidence of publication bias was present, but sensitivity analysis excluding small trials that reported extreme results only affected the pooled effect size minimally. In summary, the present meta-analysis suggested that probiotic fermented milk has BP-lowering effects in pre-hypertensive and hypertensive subjects.

Clinical features and surgical management of four peculiar cases of intracranial metastases from renal cell carcinoma.

Intracranial metastasis from renal cell carcinoma is rare. In this study, four patients (age range 56-72 years) were treated for intracranial metastases from renal cell carcinoma. The metastasis was solitary in all four patients and was located in the temporoparietal region in two patients, cerebellum in one patient, and bilateral lateral ventricles in one patient. Preoperative magnetic resonance imaging showed hemorrhage and necrosis in the tumor in all four patients, and one patient had edema in the region of the tumor. All patients were treated with craniotomy for tumor resection, and histopathologic examination showed clear cell carcinoma. Marked bleeding occurred in all patients during the operation, but preoperative direct injection of ethanol into epidural metastases (2 patients) was effective in decreasing intraoperative blood loss. Prognosis was poor with limited survival time (range 2 weeks-45 months), but prognosis was best in the two patients who were treated with postoperative radiation therapy and chemotherapy (survival times 26 and 45 months). To our knowledge, this is the largest report of four uncommon intracranial metastases from RCC in Chinese patients. In summary, intracranial metastasis from renal cell carcinoma should be considered in the differential diagnosis of intracranial tumor because of the high risk of bleeding and poor prognosis.

Immunomodulatory effects of dietary supplementation with a milk-based wolfberry formulation in healthy elderly: a randomized, double-blind, placebo-controlled trial.

Wolfberry (fruit of Lycium barbarum) has been prized for many years in China for its immunomodulatory property and its high specific antioxidant content. However, clear clinical evidence demonstrating the effect of wolfberry dietary supplementation is still lacking. After our earlier report showing that a proprietary milk-based wolfberry formulation (Lacto-Wolfberry) enhances in vivo antigen-specific adaptive immune responses in aged mice, the present study aimed at demonstrating the effect of dietary Lacto-Wolfberry supplementation on immune functions in the elderly, especially vaccine response known to decline with aging. A 3-month randomized, double-blinded, placebo-controlled study was conducted on 150 healthy community-dwelling Chinese elderly (65-70 years old) supplemented with Lacto-Wolfberry or placebo (13.7 grams/day). Immune response to influenza vaccine was assessed in the study, along with inflammatory and physical status. No serious adverse reactions were reported during the trial, neither symptoms of influenza-like infection. No changes in body weight and blood pressure, blood chemistry or cells composition, as well as autoantibodies levels were observed. The subjects receiving Lacto-Wolfberry had significantly higher postvaccination serum influenza-specific immunoglobulin G levels and seroconversion rate, between days 30 and 90, compared with the placebo group. The postvaccination positive rate was greater in the Lacto-Wolfberry group compared to the placebo group, but did not reach statistical significance. Lacto-Wolfberry supplementation had no significant effect on delayed-type hypersensitivity response and inflammatory markers. In conclusion, long-term dietary supplementation with Lacto-Wolfberry in elderly subjects enhances their capacity to respond to antigenic challenge without overaffecting their immune system, supporting a contribution to reinforcing immune defense in this population.