Flexible high-density microelectrode arrays for closed-loop brain-machine interfaces: a review.

Flexible high-density microelectrode arrays (HDMEAs) are emerging as a key component in closed-loop brain-machine interfaces (BMIs), providing high-resolution functionality for recording, stimulation, or both. The flexibility of these arrays provides advantages over rigid ones, such as reduced mismatch between interface and tissue, resilience to micromotion, and sustained long-term performance. This review summarizes the recent developments and applications of flexible HDMEAs in closed-loop BMI systems. It delves into the various challenges encountered in the development of ideal flexible HDMEAs for closed-loop BMI systems and highlights the latest methodologies and breakthroughs to address these challenges. These insights could be instrumental in guiding the creation of future generations of flexible HDMEAs, specifically tailored for use in closed-loop BMIs. The review thoroughly explores both the current state and prospects of these advanced arrays, emphasizing their potential in enhancing BMI technology.

Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease.

Dyslipidemia due to renal insufficiency is a common complication in patients with chronic kidney diseases (CKD), and a major risk factor for the development of cardiovascular events. Atorvastatin (AT) is mainly used in the treatment of dyslipidemia in patients with CKD. However, response to the atorvastatin varies inter-individually in clinical applications. We examined the association between polymorphisms in genes involved in drug metabolism and transport, and plasma concentrations of atorvastatin and its metabolites (2-hydroxy atorvastatin (2-AT), 2-hydroxy atorvastatin lactone (2-ATL), 4-hydroxy atorvastatin (4-AT), 4-hydroxy atorvastatin lactone (4-ATL), atorvastatin lactone (ATL)) in kidney diseases patients. Genotypes were determined using TaqMan real time PCR in 212 CKD patients, treated with 20 mg of atorvastatin daily for 6 weeks. The steady state plasma concentrations of atorvastatin and its metabolites were quantified using ultraperformance liquid chromatography in combination with triple quadrupole mass spectrometry (UPLC-MS/MS). Univariate and multivariate analyses showed the variant in ABCC4 (rs3742106) was associated with decreased concentrations of AT and its metabolites (2-AT+2-ATL: ß = -0.162, p = 0.028 in the dominant model; AT+2-AT+4-AT: ß = -0.212, p = 0.028 in the genotype model), while patients carrying the variant allele ABCC4-rs868853 (ß = 0.177, p = 0.011) or NR1I2-rs6785049 (ß = 0.123, p = 0.044) had higher concentrations of 2-AT+2-ATL in plasma compared with homozygous wildtype carriers. Luciferase activity was enhanced in HepG2 cells harboring a construct expressing the rs3742106-T allele or the rs868853-G allele (p < 0.05 for each) compared with a construct expressing the rs3742106G or the rs868853-A allele. These findings suggest that two functional polymorphisms in the ABCC4 gene may affect transcriptional activity, thereby directly or indirectly affecting release of AT and its metabolites from hepatocytes into the circulation.

Molecular cloning, tissues distribution, and function analysis of thioredoxin-like protein-1 (TXNL1) in Chinese giant salamanders Andrias davidianus.

Thioredoxin-like protein-1 (TXNL1) is the member of thioredoxin superfamily, a family of thiol oxidoreductases. TXNL1 plays an important role in scavenging ROS and the maintenance of cellular redox balance. However, its physiological functions in Andrias davidianus have not been well understood. In the present study, the full-length cDNA encoding thioredoxin-like protein-1 (AdTXNL1) of A. davidianus was cloned, the mRNA tissue distribution was analyzed, and the function was characterized. The Adtxnl1 cDNA contained an open reading frame (ORF) of 870 bp encoding a polypeptide of 289 amino acids with the N-terminal TRX domain, a Cys34-Ala35-Pro36-Cys37 (CAPC) motif, and the C-terminal proteasome-interacting thioredoxin domain (PITH). The mRNA of AdTXNL1 was expressed in a wide range of tissues, with the highest level in the liver. The transcript level of AdTXNL1 was significantly up-regulated post Aeromonas hydrophila challenge in liver tissue. Moreover, the recombinant AdTXNL1 protein was produced and purified, and used to investigate the antioxidant activity. In the insulin disulfide reduction assay, rAdTXNL1 exhibited strong antioxidant capability. Altogether, the thioredoxin-like protein-1 may be involved in reduction/oxidation (redox) balance and as an important immunological gene in A. davidianus.

The interaction of MC3R and MC4R with MRAP2a in rainbow trout (Oncorhynchus mykiss).

Melanocortin 3 and 4 receptors are two important neural G protein-coupled receptors that regulate energy homeostasis in vertebrates. Melanocortin receptor accessory protein 2 (MRAP2) is also involved in the regulation of food intake and body weight as a variable regulator of melanocortin receptors. Rainbow trout (Oncorhynchus mykiss) is a valuable cold-water fish cultured worldwide. In the rainbow trout model, we cloned and identified mrap2a, a paralog of mrap2. Rainbow trout mrap2a consisted of a 690 bp ORF and was expected to encode a putative protein of 229 amino acids. The qPCR results showed that rainbow trout mrap2a was expressed at high levels in brain tissue similar to mc3r and mc4r. In addition, co-immunoprecipitation verified that MRAP2a interacts with MC3R and MC4R in vitro and that MRAP2a is involved in and regulates the constitutive activity and signaling of MC3R and MC4R. MRAP2a reduced constitutive and agonist-stimulated cAMP levels of MC3R; furthermore, MRAP2a increased constitutive ERK1/2 activation but reduced ligand-induced stimulation at high levels of expression. For MC4R, MRAP2a showed decreased cAMP basal activity but increased agonist-stimulated cAMP signaling and increased ACTH ligand sensitivity. However, MRAP2a failed to affect MC4R constitutive activity and agonist-induced ERK1/2 signaling. Undoubtedly, our study will have great significance for revealing the conserved role of MC4R and MC3R signaling in teleost fish, especially in cold-water fish growth and energy homeostasis.

Functional characterization of melanocortin-3 receptor in rainbow trout (Oncorhynchus mykiss).

The melanocortin-3 receptor (MC3R) is an important regulator of energy homeostasis and inflammation in mammals. However, its function in teleost fish needs to be further explored. In this study, we characterized rainbow trout MC3R (rtMC3R), which encoded a putative protein of 331 amino acids. Phylogenetic and chromosomal synteny analyses showed that rtMC3R was closely related to bony fishes. Quantitative PCR (qPCR) revealed that the transcripts of rtMC3R were highly expressed in the brain and muscle. The cellular function of rtMC3R was further verified by the signal-pathway-specific luciferase reporter assays. Four agonists such as α-MSH, ß-MSH, ACTH (1-24), and NDP-MSH can active rtMC3R, increasing the production of intracellular cAMP and upregulating MAPK/ERK signals. Moreover, we found that rtMC3R stimulated with α-MSH and NDP-MSH can significantly inhibit the NF-κB signaling pathway. This research will be helpful for further studies on the function of MC3R in rainbow trout, especially the role of energy metabolism and immune regulation.

miR-365 inhibits the progression of gallbladder carcinoma and predicts the prognosis of Gallbladder carcinoma patients.

Gallbladder carcinoma (GBC) is one of the most common fatal biliary tract tumors in the world. Its 3-year survival rate is 30% and the recurrence rate remains very high. miR-365 was downregulated in numerous tumors and worked as tumor suppressor gene. However, the role of miR-365 in GBC was unclear. In this study, our results found that the expression of miR-365 in GBC tissues was reduced rather than that in non-cancerous tissues. miR-365 overexpression inhibited the proliferation, metastasis and expansion of GBC CSCs. Mechanically, bioinformatic and luciferase reporter analysis identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as a direct target of miR-365. Overexpression of miR-365 in GBC cells reduced the RAC1 mRNA and protein expression. The special RAC1 inhibitor EHop-106 abolished the discrepancy of growth, metastasis and self-renewal ability between miR-365-overexpression GBC cells and their control cells, which further demonstrated that RAC1 was involved in miR-365-disrupted GBC cells growth, metastasis and self-renewal. More importantly, reduced expression of miR-365 was a predictor of poor prognosis of GBC patients. In conclusion, miR-365 inhibited GBC cell growth, metastasis and self-renewal capacity by directly targeting RAC1, and may therefore prove to be a novel prognosis biomarker for GBC patients.

Effect of postoperative early enteral nutrition on clinical outcomes and immune function of cholangiocarcinoma patients with malignant obstructive jaundice.

BACKGROUND: Most cholangiocarcinoma patients with malignant obstructive jaundice (MOJ) have varying degrees of malnutrition and immunodeficiency preoperatively. Therefore, perioperative nutritional support has important clinical significance in the treatment of cholangiocarcinoma. AIM: To investigate the effects of postoperative early enteral nutrition (EEN) on immunity function and clinical outcomes of cholangiocarcinoma patients with MOJ. METHODS: This prospective clinical study included 60 cholangiocarcinoma patients with MOJ who underwent surgery. The patients were randomly divided into an experimental group and a control group according to the nutrition support modes. The control group received postoperative total parenteral nutrition (TPN), whereas the experimental group received postoperative EEN and parenteral nutrition (PN; EEN + PN). The clinical outcomes, postoperative immune function, incidences of surgical site infection and bile leakage, intestinal function recovery time, average hospitalization days, and hospitalization expenses of the two groups were assessed on postoperative days (PODs) 1, 3, and 7. RESULTS: The CD3+T, CD4+T, CD8+T, and CD4+T/CD8+T cell count and the immunoglobulin (Ig) G, IgM, and IgA levels in the EEN + PN group were significantly higher than those in the TPN group on PODs 3 and 7 (P < 0.05), whereas no significant differences in the CD3+T, CD4+T, CD8+T, and CD4+T/CD8+T cell counts and IgG, IgM, and IgA levels before operation and on POD 1 were found between the two groups (P > 0.05). The intestinal function recovery time and postoperative hospital stay were shorter (P < 0.001 for both) in the EEN + PN group than in the TPN group. The hospitalization expenses of the EEN + PN group were lower than those of the TPN group (P < 0.001). However, the incidence of abdominal distension was higher than in the EEN + PN group than in the TPN group (P < 0.05). The incidence rates of biliary leakage and surgical site infection were not significantly different between the two groups (P > 0.05). CONCLUSION: A postoperative EEN program could reduce the incidence of postoperative complications and improve the clinical outcomes and immune functions of cholangiocarcinoma patients with MOJ and is thus beneficial to patient recovery.

High expression of forkhead box M1 (FOXM1) is a poor prognostic biomarker in lung adenocarcinoma.

BACKGROUND: Forkhead box M1 (FOXM1) is closely related to the formation and development of cancer. Because of differences in cellular origin, lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SCC) usually exhibit different signatures. Therefore, it is essential to investigate the abnormalities of FOXM1 in the two subtypes separately. METHODS: Through the Oncomine and TCGA databases, we investigated the expression of FOXM1 mRNA, its prognostic value and possible mechanisms leading to its dysregulation. Furthermore, networks involving FOXM1 and its significantly altered neighboring genes were identified using the cBioPortal database. GO and KEGG enrichment analyses were performed using DAVID. RESULTS: Expression of FOXM1 mRNA was higher in lung tumor tissues than in normal tissues, and higher in SCC tissues than in ADC tissues. FOXM1 mRNA expression was correlated with N stage, TNM stage, age, sex and smoking history in ADC, but only correlated with N stage, age and sex in SCC. Survival analysis indicated that high expression of FOXM1 mRNA resulted to poor overall survival (OS) for ADC patients, but not for SCC patients. Cox regression analysis confirmed that FOXM1 mRNA expression was an independent prognostic indicator for ADC patients, and regression analysis identified a moderately positive correlation between FOXM1 mRNA levels and copy number alterations (CNAs), but a weakly negative association with DNA methylation. FOXM1 was mainly involved in cell cycle regulation, G2/M transition, G1/S transition and p53, PI3K-Akt and TGF-beta signaling pathway. CONCLUSIONS: High expression of FOXM1 mRNA might be an independent biomarker of poor OS in ADC patients.

Computer-aided diagnosis of laryngeal cancer via deep learning based on laryngoscopic images.

OBJECTIVE: To develop a deep convolutional neural network (DCNN) that can automatically detect laryngeal cancer (LCA) in laryngoscopic images. METHODS: A DCNN-based diagnostic system was constructed and trained using 13,721 laryngoscopic images of LCA, precancerous laryngeal lesions (PRELCA), benign laryngeal tumors (BLT) and normal tissues (NORM) from 2 tertiary hospitals in China, including 2293 from 206 LCA subjects, 1807 from 203 PRELCA subjects, 6448 from 774 BLT subjects and 3191 from 633 NORM subjects. An independent test set of 1176 laryngoscopic images from other 3 tertiary hospitals in China, including 132 from 44 LCA subjects, 129 from 43 PRELCA subjects, 504 from 168 BLT subjects and 411 from 137 NORM subjects, was applied to the constructed DCNN to evaluate its performance against experienced endoscopists. RESULTS: The DCCN achieved a sensitivity of 0.731, a specificity of 0.922, an AUC of 0.922, and the overall accuracy of 0.867 for detecting LCA and PRELCA among all lesions and normal tissues. When compared to human experts in an independent test set, the DCCN' s performance on detection of LCA and PRELCA achieved a sensitivity of 0.720, a specificity of 0.948, an AUC of 0.953, and the overall accuracy of 0.897, which was comparable to that of an experienced human expert with 10-20 years of work experience. Moreover, the overall accuracy of DCNN for detection of LCA was 0.773, which was also comparable to that of an experienced human expert with 10-20 years of work experience and exceeded the experts with less than 10 years of work experience. CONCLUSIONS: The DCNN has high sensitivity and specificity for automated detection of LCA and PRELCA from BLT and NORM in laryngoscopic images. This novel and effective approach facilitates earlier diagnosis of early LCA, resulting in improved clinical outcomes and reducing the burden of endoscopists.

miR-365 regulates liver cancer stem cells via RAC1 pathway.

Liver cancer stem cells (CSCs) were involved in tumorigenesis, progression, recurrence, and drug resistance of hepatocellular carcinoma (HCC). miR-365 was downregulated in hepatocellular carcinoma and inhibited HCC cell proliferation and invasion. However, the role of miR-365 in liver cancer stem cells was unknown. Herein, we observed a remarkable decrease of miR-365 expression in CD133 or EpCAM-positive liver CSCs as well as in CSC-enriched hepatoma spheres. Up-regulated miR-365 suppressed liver CSC expansion by inhibiting the dedifferentiation of hepatoma cells and decreasing the self-renewal ability of liver CSCs. Mechanistically, bioinformatic and luciferase reporter analysis identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as a direct target of miR-365. Overexpression of miR-365 in hepatoma cells downregulated the RAC1 mRNA and protein expression. RAC1 also could promote the expansion of liver CSCs. The special RAC1 inhibitor EHop-106 or RAC1 overexpression abolished the discrepancy in liver CSC proportion and the self-renewal capacity between miR-365 overexpression hepatoma cells and control cells, which further confirmed that RAC1 was required in miR-365-suppressed liver CSCs expansion. miR-365 was downregulated in liver CSCs and could inhibit HCC cells dedifferentiation and liver CSCs expansion by targeting RAC1 signaling.

Knockdown of alpha-fetoprotein expression inhibits HepG2 cell growth and induces apoptosis.

AIMS: To explore the biological roles of alpha-fetoprotein (AFP), a tumor-associated antigen in human hepatocellular carcinoma (HCC). MATERIALS AND METHODS: After knockdown of AFP in HepG2 cells by transfection of specific Stealth™ RNAi, the expression of AFP were detected by reverse transcription polymerase chain reaction at mRNA level and by enzyme-linked immunosorbent assay at the protein level. Then, the effect of silenced AFP on cell proliferation was assessed by dimethylthiazolyl-2,5-diphenyl-tetrazolium bromide assay, and apoptosis assessment with Hoechst33258 and flow cytometry (double stain with fluorescein isothiocyanate/propidium iodide), the roles of AFP in the cell cycle regulation were assessed by flow cytometry. We also detected the expression of some key proteins related to apoptosis pathway by Western immunoblot analysis. RESULTS: After the transfection for 48 h, the expression of AFP gene was almost abolished, the cell proliferation was inhibited by 47.61%, the number of cells undergoing early apoptosis was significantly increased to 59.47%; cell cycle was arrested with the increase of G0/G1 phase cells from 45.3% to 58.4%. Inhibition of AFP expression also results in decreasing of transforming growth factor-ß (TGF-ß), mutant P53 expression, and increasing of Bax/Bcl-2 ratio, activation of caspase-3. CONCLUSIONS: The results suggest that AFP may positively regulate cell proliferation by enhancing the apoptosis resistance via effect on TGF-ß and p53/Bax/caspase-3 signaling pathway in HepG2 cells. As such, the knockdown of AFP gene should be further investigated in vivo as a novel approach to HCC treatment.

Purification, partial characterization and bioactivity of sulfated polysaccharides from Grateloupia livida.

Purification, preliminary characterization and bioactivity of polysaccharides from Grateloupia livida (GL) were investigated. Three water-soluble sulfated polysaccharide fractions (GLP-1, GLP-2 and GLP-3) were isolated and purified from the edible and medicinal red seaweed, Grateloupia livida (Harv.) Yamada by DEAE Sepharose CL-6B and Sephadex G-100 column chromatography, and chemical characterization was performed by HPGPC, GC-MS, FT-IR and SEM. In addition, anticoagulant activities were determined by activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) using normal human plasma in vitro. The antioxidant activities against DPPH and ABTS+ radicals were evaluated and compared. The molecular weights of GLP-1, GLP-2 and GLP-3 were 39.5, 60.4 and 3.36kDa, respectively. Monosaccharide analysis revealed that three polysaccharide fractions were homopolysaccharides and comprised of galactose only. Anticoagulant assays indicated that crude GLP, and purified GLP-1 and GLP-2 effectively prolonged APTT and TT, but not PT. All polysaccharide fractions exhibited significant in vitro antioxidant activities in a dose-dependent manner. GLP-2 showed consistently better anticoagulant and antioxidant activities compared with GLP, GLP-1 and GLP-3. These results demonstrate that sulfated polysaccharides isolated from Grateloupia livida can serve as readily available alternative natural sources of anticoagulant and antioxidant agents.

Mir-30d increases intracellular survival of Helicobacter pylori through inhibition of autophagy pathway.

AIM: To determine if mir-30d inhibits the autophagy response to Helicobacter pylori (H. pylori) invasion and increases H. pylori intracellular survival. METHODS: The expression of mir-30d was detected by quantitative polymerase chain reaction (PCR), and autophagy level was examined by transmission electron microscopy, western blot, and GFP-LC3 puncta assay in human AGS cells and GES-1 cells. Luciferase reporter assay was applied to confirm the specificity of mir-30d regulation on the expression of several core molecules involved in autophagy pathway. The expression of multiple core proteins were analyzed at both the mRNA and protein level, and the intracellular survival of H. pylori after different treatments was detected by gentamicin protection assay. RESULTS: Autophagy level was increased in AGS and GES-1 cells in response to H. pylori infection, which was accompanied by upregulation of mir-30d expression (P < 0.05, vs no H. pylori infection). In the two gastric epithelial cell lines, mimic mir-30d was found to repress the autophagy process, whereas mir-30d inhibitor increased autophagy response to H. pylori invasion. mir-30d mimic decreased the luciferase activity of wild type reporter plasmids carrying the 3' untranslated region (UTR) of all five tested genes (ATG2B, ATG5, ATG12, BECN1, and BNIP3L), whereas it had no effect on the mutant reporter plasmids. These five genes are core genes of autophagy pathway, and their expression was reduced significantly after mir-30d mimic transfection (P < 0.05, vs control cells without mir-30d mimic treatment). Mir-30d mimic transfection and direct inhibition of autophagy increased the intracellular survival of H. pylori in AGS cells. CONCLUSION: Mir-30d increases intracellular survival of H. pylori in gastric epithelial cells through inhibition of multiple core proteins in the autophagy pathway.

Optimized Extraction of Polysaccharides from Grateloupia livida (Harv.) Yamada and Biological Activities.

Polysaccharides from Grateloupia livida (Harv.) Yamada (GL) were extracted by a heating circumfluence method. Single-factor experiments were performed for the three parameters: extraction time (X1), extraction temperature (X2) and the ratio of water to raw material (X3) and their test range. From preliminary experimental results, one type of the response surface methodology, the Box-Behnken design was applied for the optimizing polysaccharide extraction conditions. The experimental data obtained were fitted to a second-order polynomial equation. The optimal conditions were extraction time 5 h, extraction temperature 100 °C and ratio of water to raw material 70 mL/g. Under these conditions, the experimental yield was 39.22% ± 0.09%, which well matched the predicted value (39.25%), with 0.9774 coefficient of determination (R²). GL polysaccharides had scavenging activities for DPPH and hydroxyl radicals in vitro. The scavenging rates for both radicals peaked at 20 mg/mL GL concentration. However, the positive standard, VC (ascorbic acid), possessed stronger antioxidant activities than GL polysaccharides. Furthermore, the anticancer activity of GL polysaccharides on HepG2 cell proliferation increased dose- and time-dependently, but the positive standard, 5-fluorouracil (5-fu) showed more significant anticancer activity in this study. Overall, GL polysaccharides may have potential applications in the medical and food industries.

Inhibition of c-Myc by let-7b mimic reverses mutidrug resistance in gastric cancer cells.

Chemotherapy is one of the few effective choices for patients with advanced or recurrent gastric cancer (GC). However, the development of mutidrug resistance (MDR) to cancer chemotherapy is a major obstacle to the effective treatment of advanced GC. Additionally, the mechanism of MDR remains to be determined. In the present study, we tested IC50 of cisplatin (DDP), vincristine (VCR) and 5-fluorouracil (5-FU) in SGC7901, SGC7901/DDP and SGC7901/VCR gastric cancer cells using an MTT assay. The expression of let-7b and c-Myc in these cells was detected by qPCR and western blot analysis. The relationship between let-7b and c-Myc was explored using a luciferase reporter assay. Transfection of let-7b mimic or inhibitor was used to confirm the effect of let-7b on drug sensitivity in chemotherapy via the regulation of c-Myc expression. We found that the expression of let-7b was lower in chemotherapy-resistant SGC7901/DDP and SGC7901/VCR gastric cancer cells than that in chemotherapy-sensitive SGC7901 cells. By contrast, the expression of c-Myc was higher in SGC7901/DDP and SGC7901/VCR cells than that in SGC7901 cells. Furthermore, we confirmed that let-7b suppresses c-Myc gene expression at the mRNA and protein levels in a sequence-specific manner, while transfection of let-7b mimic increases drug sensitivity in chemotherapy-resistant SGC7901/DDP and SGC7901/VCR cells by targeting downregulation of c-Myc. In SGC7901 drug-sensitive cells, however, the sensitivity of chemotherapy was significantly decreased following let-7b inhibitor transfection. The present study results demonstrated that let-7b increases drug sensitivity in chemotherapy­resistant SGC7901/DDP and SGC7901/VCR gastric cancer cells by targeting the downregulation of c-Myc and that, let-7b mimic reverses MDR by promoting cancer stem cell differentiation controlled by double-negative autoregulatory loops (Lin28/let-7 and Myc/let-7) and a double-positive autoregulatory loop (Lin28/Lin28B/Myc) existing in GC cells, which remains to be confirmed.

Egg consumption and breast cancer risk: a meta-analysis.

The relationship between egg consumption and breast cancer risk has been inconsistent, so it is necessary to conduct a meta-analysis to evaluate the relationship. PubMed, EMBASE and ISI Web of Knowledge were searched to find cohort studies or case control studies that evaluated the relationship between egg consumption and breast cancer risk. A comprehensive meta-analysis software was used to conduct the meta-analysis. 13 studies were included. The meta-analysis results showed that egg consumption was associated with increased breast cancer risk (RR 1.04, 95 % CI 1.01-1.08). Subgroup analyses showed egg consumption was also associated with increased breast cancer risk based on cohort studies (RR 1.04, 95 % CI 1.00-1.08), among European population (RR 1.05, 95 % CI 1.01-1.09), Asian population (RR 1.09, 95 % CI 1.00-1.18), postmenopausal population (RR 1.06, 95 % CI 1.02-1.10), and those who consumed ≥2, ≤5/week (RR 1.10, 95 % CI 1.02-1.17), but not in case-control studies (RR 1.06, 95 % CI 0.97-1.15), among American population (RR 1.04, 95 % CI 0.94-1.16), premenopausal population (RR 1.04, 95 % CI 0.98-1.11) and those who consumed ≥1, <2/week (RR 1.04, 95 % CI 0.97-1.11) or >5 eggs/week (RR 0.97, 95 % CI 0.88-1.06). Egg consumption was associated with increased breast cancer risk among the European, Asian and postmenopausal population and those who consumed ≥2, ≤5/week.

Antioxidant, antibacterial and antischistosomal activities of extracts from Grateloupia livida (Harv). Yamada.

The present study was designated to evaluate the antioxidant, antibacterial and antischistosomal activities of Grateloupia livida (GL) extracts in vitro. A GL Ethanol extract (EE) was separated into petroleum ether (PE), ethyl acetate (EA), n-butyl alcohol (BuOH) and aqueous (AQ) fractions to fractionate the polar and non-polar compounds in the EE. Extracts antioxidant activities were evaluated in vitro by DPPH radical-scavenging, deoxyribose radical scavenging, and ß-carotene bleaching assays, all using butylated hydroxytoluene (BHT) as the reference antioxidant compound. The most effective antioxidant properties were observed in the PE fraction in all three assays. Antimicrobial testing showed that the PE fraction exhibited broad-spectrum antimicrobial activity, with the PE fraction also exhibiting strong activity against the human pathogenic trematode S. japonicum adult worm. In order to investigate the relationships between bioactivity and chemical composition, the chemical composition of the PE fraction was analyzed by gas chromatography-mass spectrometry (GC-MS). In total, 25 components were identified in the PE fraction, most of which have known antioxidant and antimicrobial activities. However, none of the compounds have reported activity against Schistosoma, suggesting that the schistosomicidal activity of the PE fraction may be related to minor constituents present in the extract, or governed by more intricate synergistic or additive relationships. Finally, fractions with the greatest biological activity displayed neither cellular cytotoxicity, at concentrations up to 100 ug/ml, or acute oral toxicity in mice, at doses up to 2000 mg/kg. Based on antioxidant, antimicrobial, antischistosomal activities, and low toxicity, the PE fraction possesses properties useful for food preservation and overall improvement of human health.