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The article discusses study on association of cAMP response element binding protein (CREB1) and CBP genes with Alzheimer's disease in Han Chinese. It mentions no significant difference in allele and genotype frequencies between the case and control groups in either eastern China or southwestern China populations. It adds they may not play major roles in the pathophysiology of the disease.

ICPC-a was from the Imperata cylindrica with a molecular weight of 45 kDa, which was composed of α-D-1,3-Glc p and α-D-1,6-Glc p. The ICPC-a showed thermal stability, maintaining its structural integrity up to 220°C. X-ray diffraction analysis confirmed its amorphous nature, while scanning electron microscopy revealed a layered morphology. ICPC-a significantly ameliorated uric acid stimulation-induced HK-2 cell injury and apoptosis and reduced uric acid levels in mice with hyperuricemic nephropathy. ICPC-a protected against renal injury by inhibiting lipid peroxidation levels, increasing antioxidant damage and defense levels, inhibiting secretion of pro-inflammatory factors, regulating purine metabolism, PI3K-Akt signaling pathway, NF-κB signaling pathway, inflammatory bowel disease, mTOR signaling pathway, and MAPK signaling pathway. These findings indicate that ICPC-a is a promising natural substance with multiple targets, multiple pathways of action, and without toxicity, making it a valuable subject for further research and development. [Display omitted] [ABSTRACT FROM AUTHOR]

A water-soluble polysaccharide was isolated from marine green algae Ulva pertusa and then chelated with iron to prepare the polysaccharide‑iron (III) complex. The immunomodulatory activities of sulfated polysaccharide and polysaccharide‑iron (III) complex were investigated through a mice immune-deficiency model. Cyclophosphamide (Cy) was utilized to establish mice immunodeficiency model. Both polysaccharide and polysaccharide‑iron (III) complex were proved to promote the proliferation of lymphocyte and enhance the activities of mice macrophages. In mice serum, the levels of cytokines including TNF-α, IFN-γ and IL-10 restored and the contents of hemolysin were also found elevated after treatment with polysaccharide and its iron complex. Besides, it has been shown that both polysaccharide and polysaccharide‑iron (III) complex increased the contents of Hb, RBC and HCT in mice blood, and the effect of iron complex was better. All these results suggested that Ulva pertusa polysaccharide could be developed as a healthy function food. It was also noteworthy that the polysaccharide‑iron (III) complex showed no negative effect upon the immunomodulatory activity of polysaccharide. Instead, the polysaccharide‑iron (III) complex showed excellent hematopoietic capacity perhaps due to the supplement of iron. [ABSTRACT FROM AUTHOR]

In this study, the peptides of soy protein obtained by enzymatic digestion with proteases were analyzed for their antidiabetic, antihypertensive, and antioxidant activities. Peptides prepared with alkaline proteinase (AP) exhibited the highest α‐glucosidase inhibitory activity compared with those from papain and trypsin digestion. AP hydrolysates also exhibited dipeptidyl peptidase IV (DPP‐IV) inhibitory, angiotensin‐converting enzyme (ACE) inhibitory, and antioxidant activities. Gastrointestinal digestion of peptides enhanced α‐glucosidase, DPP‐IV, and ACE inhibitory activities compared with AP hydrolysates. AP peptides showing highest α‐glucosidase inhibitory activity were purified by anion‐exchange and size‐exclusion chromatography， and identified using tandem MS. We found three novel α‐glucosidase inhibitory peptides with sequences LLPLPVLK, SWLRL, and WLRL with IC50 of 237.43 ± 0.52, 182.05 ± 0.74, and 162.29 ± 0.74 μmol/L, respectively. Therefore, peptides hydrolyzed from soy protein are promising natural ingredients for nutraceutical applications assisting in the management of diabetes. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HAP) was very attractive for using as bone implant material for a long period due to the close similarity with natural bone in composition and osteoconductive properties. In this study, three kinds of natural HAP (nHAP) derived from rainbow trout ( Onchorynchus mkiss ), cod ( Gadus ) and salmon ( Oncorhynchus keta ) bones were prepared using thermal calcination method for the first time. Resultant nHAPs were characterized by fourier transform infrared spectroscopy (FT-IR), x-ray diffraction analysis (XRD), field-emission scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) analysis. Biocompatibility of calcined nHAP was evaluated through MTT cell viability assay and alkaline phosphatase activity experiment using mouse preosteoblast MC3T3-E1. Results of cell experiment indicated that the nHAP originated from rainbow trout and salmon bones showed better biological compatibility compared with the nHAP originated from cod bone and chemical synthetic HAP (cHAP). This is most likely attributed to the different element composition in nHAP, i.e., the nHAP derived from rainbow trout and salmon bones showed the presence of CO 3 2– and Mg 2+ . Therefore, the nHAP originated from rainbow trout and salmon bones have a great potential for application as implant material substitute in bone tissue engineering and the natural waste fish bone product can be used for hydroxyapatite synthesis as a part of bio-waste management. [ABSTRACT FROM AUTHOR]

Various bioactive peptides are continuously being identified from casein hydrolysates. In this work, a novel angiotensin I-converting enzyme (ACE)-inhibitory (ACEI) peptide, NMAINPSKENLCSTFCK, derived from the α s2 -casein fragment residues 25–41, was screened and identified by UPLC-ESI-Q-TOF-MS/MS from tryptic casein hydrolysate. The IC 50 value of the peptide, determined by an HPLC method, was 129.07 μM. The Lineweaver-Burk plot showed that this peptide acted as a mixed-type inhibitor against ACE, which might be attributed to the peptide being susceptible to degradation by ACE, indicating that the mixed-type inhibition could partly be a result of newly generated peptide fragments. The physicochemical characteristics and the secondary structure were evaluated by circular dichroism analysis and online prediction software (Expasy, PepDraw, and ProtParam) to identify the basic characteristics of this peptide. Moreover, molecular docking was simulated by Discovery Studio 2017 R2 software to provide the potential mechanisms underlying the ACEI activity of the peptides. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effect of sweet tea polysaccharide (STP) on the physicochemical and structural properties of heat-induced whey protein isolate (WPI) gels, and explored the potential mechanism. The results indicated that STP promoted the unfolding and cross-linking of WPI to form a stable three-dimensional network structure, and significantly improved the strength, water-holding capacity and viscoelasticity of WPI gels. However, the addition of STP was limited to 2 %, too much STP would loosen the gel network and affect the gel properties. The results of FTIR and fluorescence spectroscopy suggested that STP affected the secondary and tertiary structures of WPI, promoted the movement of aromatic amino acids to the protein surface and the conversion of α-helix to β-sheet. In addition, STP reduced the surface hydrophobicity of the gel, increased the free sulfhydryl content, and enhanced the hydrogen bonding, disulfide bonding, and hydrophobic interactions between protein molecules. These findings can provide a reference for the application of STP as a gel modifier in the food industry. [ABSTRACT FROM AUTHOR]

Abstract: BACKGROUND: Bioactive casein peptides have attracted considerable attention for their applications in industry. However, there is little clarity regarding mass spectrometric profiles for peptides in enzymatic hydrolysates of casein produced under varying conditions. In this study, the compositions of the peptides from casein hydrolysates were compared for different enzyme/substrate ratio (E/S) and hydrolysis times. The toxicity, allergenicity and bioactivity of the identified peptides were assessed in silico. RESULTS: A total of 70 unique peptides were identified, and there were 28, 21, 13 and 8 peptides from αs1‐casein, αs2‐casein, β‐casein and κ‐casein respectively. The peptide number decreased with the increase in E/S and hydrolysis time. Moreover, peptides with relative molecular mass Mr ranging from 1000 to 1500 Da occupied the highest proportion of 31.43%, and almost all of the peptides showed Mr less than 5000 Da. In silico analysis showed that all of the peptides were non‐toxic and non‐allergenic, and several of them were assessed by PeptideRanker as having a relatively high likelihood of being bioactive peptides. CONCLUSIONS: Composition of the peptides in the casein hydrolysates varied with the enzymolysis conditions. This study's results may facilitate the production of target bioactive peptides by controlling E/S and hydrolysis time, which is beneficial for the application of casein peptides in the functional food industry. © 2017 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Abstract: Milk protein concentrate (MPC) is a widely used material in the food industry. However, despite its widespread use, the mechanism underlying the decreased solubility of MPC that occurs during storage has not yet been clarified. In this study, the solubility changes, protein cross‐linking, and Maillard reaction and the relationships between them were investigated in modified MPC powders (MMPC) containing different concentrations of protein and/or lactose stored at 50°C for 15–45 days. The results demonstrated that both the protein and lactose contents affected solubility. The proteins interacted through hydrogen bonding, disulfide bonding, hydrophobic interactions, and nondisulphide covalent bonding, which led to cross‐linking. The Maillard reaction promoted protein cross‐linking and was in turn influenced by protein cross‐linking. The Maillard reaction was slower when the degree of protein cross‐linking was greater. These results improve our understanding of the mechanism leading to poor solubility of MPC powders during storage. [ABSTRACT FROM AUTHOR]

Surface-layer associated proteins (SLAP) of Lactobacillus paracasei ssp. paracasei M5-L and Lactobacillus casei Q8-L were examined to identify the functional basis for their protection within intestinal epithelial cells. The results showed that SLAP of M5-L and Q8-L remained active in a trypsin solution and retained a 45- kDa protein band, similar to that observed in controls. In contrast, under conditions of simulated gastric juice, the SLAP were partially degraded. Inhibitory effects of SLAP on adherence of Shigella sonnei to HT-29 cells were assessed with use of exclusion, competition, and replacement assays. In response to M5-L at 50 µg/mL SLAP, an inhibition ratio of 33% was obtained, while for Q8-L at 400 µg/mL SLAP, the inhibition ratio was 48%. Hoechst 33258 test results showed that cells infected with S. sonnei and co-incubated with SLAP of M5-L and Q8-L were only partially apoptotic, with apoptosis rates of 37.67 and 43.67%, respectively. These levels of apoptosis were substantially lower than that observed with cells infected with S. sonnei alone. In addition, the SLAP of Q8-L and M5-L reduced downstream caspase-1 activity and further modified apoptotic cell damage. Finally, SLAP of M5-L and Q8-L were also able to prevent S. sonnei-induced membrane damage by inhibiting delocalization of zonula occludens (ZO)-1 and reducing the amount of occludin produced by S. sonnei. [ABSTRACT FROM AUTHOR]

The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse. Therefore, there were higher pharmacokinetic parameters-AUC, MRT, and t1/2 of the two compounds in radiation-injured mouse, when compared with normal mouse. In order to investigate the intrinsic mechanism of AS on radiation injury, AS extract's protective effects on brain, the main part of mouse that suffered from radiation, were explored. The function of AS extract in repressing expression changes of radiation response proteins in prefrontal cortex (PFC) of mouse brain included tubulin protein family (α-, β-tubulin subunits), dihydropyrimidinase-related protein 2 (CRMP2), γ-actin, 14-3-3 protein family (14-3-3ζ, ε), heat shock protein 90β (HSP90β), and enolase 2. The results demonstrated the AS extract had positive effects on nerve cells' structure, adhesion, locomotion, fission, and phagocytosis, through regulating various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol 3 kinase/protein kinase B), Neurotrophin, Rap1 (Ras-related protein RAP-1A), gap junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1) signaling pathways to maintain normal mouse neurological activity. All of the results indicated that AS may be a promising alternative medicine for the treatment of radiation injury in mouse brain. It would be tested that whether the bioactive ingredients of AS could be effective through the blood-brain barrier in the future. [ABSTRACT FROM AUTHOR]

Diosmin is the aglycone moiety of diosmetin (3′,5,7 trihydroxy-4′methoxy radicals flavonoids), a naturally occurring flavone glycoside, whose antithrombotic effect was studied in rats. This study was designed to find the protein changes of venous thrombosis in Wistar rats comparing conditions with and without Diosmin treatment by two-dimensional gel electrophoresis (2-DE), and investigate the effect of a crucial protein known as CEP350 on human vascular endothelial cell growth. Through prior chromatographic purification with macroporous absorption resin (AB-8) and polyamide, Diosmin was isolated from Galium verum L. by solvent extraction, then purified to 98% purity using HPLC. Wistar rats were divided into control group, model group, and prevention group. And their venous thrombosis tissue segments were dissected and prepared for histopathological examination and detection of plasma protein C (PC). Next, proteomic analysis was performed with the samples. Low-abundance proteins of the three groups were separated by two-dimensional gel electrophoresis (2-DE). 2-DE analysis revealed that 191 protein spots were differentially expressed among those three groups. For protein identification, we selected six spots to use matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) detection, and then do the homology search in NCBI database. Considering characteristics of these proteins, we proposed CEP350 is related to spindle assembly. Furthermore, we used Lipofectamine 2000 to transfect HUVECs with CEP350 siRNA and evaluated the extent of silencing using real time–polymerase chain reaction (RT-PCR). Cells were stained for immunofluorescence with tubulin-tracker red, and structural changes were analyzed using laser scanning confocal microscope. We concluded that CEP350 depletion decreased microtubule stability. Dosmin could modulate the assemble of spindle from unevenly distributing and protect body from varicose veins by regulating CEP350. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) has been recently recognized as a promising new novel bone growth factor for the beneficial effects on bone cells and promotion of bone growth. Currently, it has been attracted wide attention in bone regeneration as functional food additives or a potential bioactive protein in bone tissue engineering. The present study investigated the possibility that hydroxyapatite (HAP) particles, a widely used bone substitute material for high biocompatibility and osteoconductivity, functionalized with lactoferrin as a composite material are applied to bone tissue engineering. Two kinds of hydroxyapatite samples with different sizes, including nanorods and microspheres particles, were functionalized with lactoferrin molecules, respectively. A detailed characterization of as-prepared HAP-LF complex is presented, combining thermal gravimetric analysis (TGA) and Fourier Transform Infrared Spectroscopy (FT-IR). Zeta potential and the analysis of electrostatic surface potential of lactoferrin were carried to reveal the mechanism of adsorption. The effects of HAP-LF complex on MC3T3-E1 osteoblast proliferation and morphology were systematically evaluated at different culture time. Interestingly, results showed that cell viability of HAP-LF group was significantly higher than HAP group indicating that the HAP-LF can improve the biocompatibility of HAP, which mainly originated from a combination of HAP-LF interaction. These results indicated that hydroxyapatite particles can work as a controlled releasing carrier of lactoferrin successfully, and lactoferrin showed better potentiality on using in the field of bone regeneration by coupling with hydroxyapatite. This study would provide a new biomaterial and might offer a new insight for enhancement of bone regeneration. [ABSTRACT FROM AUTHOR]

Background: Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and can lead to significant psychosocial functional impairment. Although the pathogenesis of major depressive disorder (MDD) and SSD still remains poorly understood, a set of studies have found that many same genetic factors play important roles in the etiology of these two disorders. Nowadays, the differential gene expression between MDD and SSD is still unknown. In our previous study, we compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD and matched healthy controls (8 subjects in each group), and finally determined 48 gene expression signatures. Based on these findings, we further clarify whether these genes mRNA was different expressed in peripheral blood in patients with SSD, MDD and healthy controls (60 subjects respectively) Method: With the help of the quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR), we gained gene relative expression levels among the three groups. Results: We found that there are three of the forty eight co-regulated genes had differential expression in peripheral blood among the three groups, which are CD84, STRN, CTNS gene (F = 3.528, p = 0.034; F = 3.382, p = 0.039; F = 3.801, p = 0.026, respectively) while there were no significant differences for other genes. Conclusion: CD84, STRN, CTNS gene may have significant value for performing diagnostic functions and classifying SSD, MDD and healthy controls. [ABSTRACT FROM AUTHOR]

Complement pathway activation was found to occur frequently in schizophrenia, and complement 3 (C3) plays a major role in this process. Previous studies have provided evidence for the possible role of C3 in the development of schizophrenia. In this study, we hypothesized that the gene encoding C3 (C3) may confer susceptibility to schizophrenia in Han Chinese. We analyzed 7 common single nucleotide polymorphisms (SNPs) of C3 in 647 schizophrenia patients and 687 healthy controls. Peripheral C3 mRNA expression level was measured in 23 drug-naïve patients with schizophrenia and 24 controls. Two SNPs (rs1047286 and rs2250656) that deviated from Hardy-Weinberg equilibrium were excluded for further analysis. Among the remaining 5 SNPs, there was no significant difference in allele and genotype frequencies between the patient and control groups. Logistic regression analysis showed no significant SNP-gender interaction in either dominant model or recessive model. There was no significant difference in the level of peripheral C3 expression between the drug-naïve schizophrenia patients and healthy controls. In conclusion, the results of this study do not support C3 as a major genetic susceptibility factor in schizophrenia. Other factors in AP may have critical roles in schizophrenia and be worthy of further investigation. [ABSTRACT FROM AUTHOR]

Background Although the treatment guidelines of bipolar disorders (BPD) have spread more than a decade, the concordance with evidence-based guidelines was typically low in routine clinical practice. This study is to present the data on the maintenance treatment of BPD in mainland China. Methods One thousand and twenty-three patients who had experienced a euthymia were eligible for entry into this survey on the maintenance treatment of BPD. Guidelines disconcordance was determined by comparing the medication(s) that patients were prescribed with the recommendations in the guidelines of the Canadian Network for Mood and Anxiety Treatments. Results Three hundred and sixty-four patients (35.6%) had not been prescribed with the maintenance treatment as guidelines recommendations, and 208 patients (20.3%) were prescribed with the antidepressants. A longer duration of BPD, a depressive episode at first onset, and a recent depressive or mixed episode significantly increased the risk for guidelines disconcordance and prescribing antidepressant. In contrast, a hospitalization history due to manic episode was associated with a significant decrease in the risk for guidelines disconcordance and prescribing antidepressant. Limitation This study was a cross-sectional and retrospective investigation based on medical records. Conclusions Considering the potentially hazardous effects of inappropriate treatment, individualized psychoeducational strategies for subjects with BPD are necessary to enhance treatment adherence and close the gap between guidelines and clinical practice in mainland China. [ABSTRACT FROM AUTHOR]

In this study, an inulin-type fructan (PGPI-1-a) was isolated from the roots of Platycodon grandiflorum. PGPI-1-a was composed of (2 → 1)-linked β-D-fructofuranose (Fruf) and a terminal α- d -glucopyranose (Glcp) with a molecular weight of 12.1 kDa. PM2.5 exposure has brought a great threat to human health in recent years. Therefore, this study explored the effect of PGPI-1-a on the intestinal microbial community structure of rats exposed to PM2.5 using the animal model of PM2.5 inhalation exposure. The results showed that PGPI-1-a could regulate the intestinal microbiota by partly restoring the perturbed levels of Peptoniphilaceae_[G-2] and Lachnospiraceae_[G-2] caused by PM2.5 exposure. In addition, the relative abundance of Butyrivibrio , a butyric acid-producing genera, significantly increased after PGPI-1-a intervention. These results indicated that PGPI-1-a could improve the imbalance of intestinal microbiota due to PM2.5 exposure to a certain extent. [Display omitted] [ABSTRACT FROM AUTHOR]

Schizophrenia is a prevalent psychiatric disorder with a complex etiology. Mitochondrial dysfunction has been frequently reported in schizophrenia. Phosphatase and tension homologue-induced kinase 1 (PINK1) and presenilin-associated rhomboid-like protease (PARL) are mitochondrial proteins, and genetic variants of these two genes may confer genetic susceptibility to schizophrenia by influencing mitochondrial function. In this study, we conducted a two-stage genetic association study to test this hypothesis. We genotyped 4 PINK1 and 5 PARL genetic variants and evaluated the potential association of the 9 SNPs with schizophrenia in two independent case-control cohorts of 2510 Han Chinese individuals. No positive association of common genetic variants of the PINK1 and PARL genes with schizophrenia was identified in our samples after Bonferroni correction. Re-analysis of the newly updated Psychiatric Genetics Consortium (PGC) data sets confirmed our negative result. Intriguingly, one PINK1 SNP (rs10916832), which showed a marginally significant association in only Hunan samples ( P = 0.032), is associated with the expression of a schizophrenia susceptible gene KIF17 according to the expression quantitative trait locus (eQTL) analysis. Our study indicated that common genetic variants of the PINK1 and PARL genes are unlikely to be involved in schizophrenia. Further studies are essential to characterize the role of the PINK1 and PARL genes in schizophrenia. [ABSTRACT FROM AUTHOR]

Epidemiological studies have indicated that both maternal bacterial and viral infections during pregnancy increase the risk of schizophrenia among offspring, but to date there is not clear explanation for this increased risk. Previously, the decreased C4b-binding protein (C4BP), a potent circulating soluble inhibitor of the classical and lectin pathways of complement, was reported to be associated with risk of schizophrenia. Here, we analyzed 4 common single nucleotide polymorphisms (SNPs) of C4BPB and 5 SNPs of C4BPA in a group of 556 schizophrenia patients and a matched group of 610 healthy controls to see if the genes C4BPB and C4BPA, which encode C4BP, may confer a susceptibility to schizophrenia. Comparing the genotype and allele frequencies of those SNPs between cases and controls, we found no association between the C4BPB / C4BPA variants and schizophrenia. Our results provided preliminary evidence that C4BPB / C4BPA may not confer susceptibility to schizophrenia among Han Chinese. Further genetic studies from large-scale population are required to obtain more conclusive results. [ABSTRACT FROM AUTHOR]

Acanthopanax senticosus (AS) is a medicinal and food homologous plant with many biological activities. In this research, we generated a brain injury model by 60Co -γ ray radiation at 4 Gy, and gavaged adult mice with the extract with AS, Acanthopanax senticocus polysaccharides (ASPS), flavones, syringin and eleutheroside E (EE) to explore the therapeutic effect and metabolic characteristics of AS on the brain injury. Behavioral tests and pathological experiments showed that the AS prevented the irradiated mice from learning and memory ability impairment and protected the neurons of irradiated mice. Meanwhile, the functional components of AS increased the antioxidant activity of irradiated mice. Furthermore, we found the changes of neurotransmitters, especially in the EE and syringin groups. Finally, distribution and pharmacokinetic analysis of AS showed that the functional components, especially EE, could exert their therapeutic effects in brain of irradiated mice. This lays a theoretical foundation for the further research on the treatment of radiation-induced brain injury by AS. [ABSTRACT FROM AUTHOR]

Sweet tea (Rubus Suavissmus S. Lee) is consumed as herbal tea in southwestern China, which has multiple functions such as relieving cough, alleviating allergic responses, and clearing away heat. Here we report the structure and lipid-lowering activity of a sweet tea polysaccharide (STP-60a). STP-60a is a homogeneous heteropolysaccharide with a molecular weight of 9.16 × 104 Da, and composed of rhamnose, arabinose, glucose, galactose and glucuronic acid. The main backbone of STP-60a consists of β-L-Rha p -(1→, →3)-β-D-Gal p -(1→, →4)-β-D-Glc p -UA-(1→, →3,6)-β-D-Gal p -(1→, →6)-β-D-Gal p -(1→, →3)-4-OAc-β-L-Ara p -(1→, →3)-α-L-Ara f -(1→ and the side chain are α-L-Ara f -(1→ and →3)-α-D-Glc p -(1→. Using Caenorhabditis elegans (C. elegans) in a high-sugar diet as a model, we found that STP-60a significantly reduced the fat accumulation in the intestine of C. elegans , and extensively affected lipolysis, fatty acid synthesis and β-oxidation processes. In addition, sbp-1 and nhr-49 were essential for STP-60a to exert a lipid-lowering effect. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights: [•] A two-stage study aimed at identifying association of LRRK2 with schizophrenia. [•] 12 LRRK2 SNPs were analyzed in Han Chinese with and without schizophrenia. [•] Genotype, allele and haplotype frequencies were compared between cases and controls. [•] None of the 12 analyzed SNPs showed a positive association with schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: Neuropsychological endophenotype approach is an emerging strategy in schizophrenia research to understand and identify the functional importance of genetically transmitted, brain-based deficits present in this disorder. Accumulating evidence indicated that working memory deficit is a core neuropsychological dysfunction in schizophrenia and a primary endophenotype indexing the liability to develop schizophrenia. Genetic variation in ankyrin 3 gene (ANK3) is likely to have widespread cognitive effects. Our previous study has identified a significant association of ANK3 SNPs and schizophrenia. In this study, we aimed to examine whether the schizophrenia-risk SNPs within ANK3 may affect working memory deficits in schizophrenia patients. Herein, we assess the working memory performance in 163 patients with first-episode, antipsychotic-naïve schizophrenia and 42 sex, age-matched healthy subjects using N-back task. Two SNPs rs10761482 and rs10994336 were genotyped among the patients and 209 controls. Our results showed that schizophrenia patients showed significantly poorer performance than healthy controls on N-back task (ps<0.01). After adjusting for the scores of intelligence quotient, memory quotient and the demographic factors, there was a significant genotype effect of the rs10994336 on the accuracy rate and reaction time of 2-back item (p =0.048 and 0.024, respectively). Post-hoc analyses showed that patients with rs10994336T/T genotype had significantly lower accuracy rate and more reaction time at 2-back task than those with T/C and C/C genotypes. The association of SNP rs10994336 with schizophrenia was replicated in our sample (genotypic p =0.024 and allelic p =0.006). However, we did not find any significant association of rs10761482 with schizophrenia and parameters in N-back task. Our results indicated that genetic variation within ANK3 may exert gene-specific modulating effects on working memory deficits in schizophrenia. [Copyright &y& Elsevier]

With the recent attention to the importance of evidence-based medicine in psychiatry, a number of treatment guidelines have been published. This survey investigated prescribing pattern and predictors for guideline disconcordance in the acute treatment of bipolar depression across mainland China. Pharmacological treatments of 1078 patients with bipolar depression were examined. Guidelines disconcordance was determined by comparing the medication(s) patients were prescribed with the recommendation(s) in the guidelines of the Canadian Network for Mood and Anxiety Treatments. Predictors for guidelines discordance were analyzed with logistic regression. Of the 1078 patients, 50.2% patients were treated against treatment guidelines recommendations. The patients who were treated in general hospitals (OR = 1.53, 95% CI 1.18–1.97), with a depressive episode (OR = 1.67, 95% CI 1.27–2.19) and an older age at first onset (OR = 1.62, 95% CI 1.15–2.28) were more likely to receive guideline-disconcordant treatment than their counterparts. In contrast, the patients with current mental comorbidity, an older age at study entry, a longer duration of disease, and more frequent episodes in past year were less likely to receive guideline-disconcordant treatments than their counterparts with an OR of 0.43 (95% CI 0.24–0.77), 0.52 (95CI% 0.36–0.75), 0.48 (95% CI 0.36–0.65), and 0.50 (95% CI 0.38–0.64), respectively. Our finding suggested the disconcordance with treatment guidelines in patients with an acute bipolar depression is common under naturalistic conditions in mainland China, and the predicting factors correlated with guidelines disconcordance include both psychiatrist-specific (clinicians from general hospitals) and patient-specific features (a depressive episode at first onset, no current co-morbidity with mental disorders, a younger age at study entry, an older age at first onset, shorter duration of disease, and non-frequent episodes in past year). [ABSTRACT FROM AUTHOR]

In this study, we examined whether common variants in the G protein-coupled receptor kinase 6 gene ( GRK6) confers susceptibility to schizophrenia in Chinese. We genotyped two common variants in 697 schizophrenia patients and 563 healthy control subjects. No significant difference in either allele or genotype comparisons between the case and control groups was found. Our results imply that GRK6 may not play a role in the pathophysiology of schizophrenia among Han Chinese. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Rationale: Clinical observations indicate that atypical antipsychotics, especially clozapine, induce obsessive-compulsive (OC) symptoms in schizophrenia patients. Recent data from neuroimaging and clinical trials suggest a role for altered glutamate neurotransmission in the etiology of OC disorder (OCD), and SLC1A1, GRIN2B, and GRIK2 have all been reported to regulate glutamate transmission and affect OCD pathophysiology. Objectives: This study aimed to determine whether SLC1A1, GRIN2B, and GRIK2 are associated with clozapine-induced OC symptoms. Methods: A total of 250 clinically stable schizophrenia patients receiving clozapine treatment were recruited. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to evaluate the severity of OC symptoms. Based on their Y-BOCS scores, 250 patients were divided into the OC and non-OC groups (patients with or without OC symptoms, respectively). Additionally, three reported OCD susceptibility polymorphisms, SLC1A1 (rs2228622), GRIN2B (rs890), and GRIK2 (rs1556995), were genotyped. Results: Trends of association with OC symptoms were observed in rs2228622A and rs890T alleles. SLC1A1 and GRIN2B interaction was found in the significant two-locus gene-gene interaction model ( p = 0.0021), using the multifactor dimensionality reduction method. Further analysis showed a significant interaction between SLC1A1 and GRIN2B on the Y-BOCS score ( F = 7.650, p < 0.001), and individuals with AA/TT genotypes had a significantly higher mean Y-BOCS score than those with other genotypes, except AG/TT. Conclusions: These results suggest that SLC1A1, GRIN2B, and interactions between the two may potentially confer a susceptibility to OC symptoms in schizophrenia patients receiving clozapine. [ABSTRACT FROM AUTHOR]

Abstract: Polysaccharides with different molecular weights were extracted from Ulva pertusa and fractionated by ultrafiltration. Iron(III) complex of the low molecular-weight U. pertusa polysaccharides were synthesized. Atomic absorption spectrum showed that the iron content of iron(III)–polysaccharide complex was 27.4%. The comparison between U. pertusa polysaccharides and their iron(III) complex showed that iron chelating altered the structural characteristics of the polysaccharides. The bioactivity analysis showed that polysaccharide with low molecular weight was more effective than polysaccharide with high molecular weight in protecting mice from radiation induced damages on bone marrow cells and immune system. Results also proved that the anti-radiation and anti-oxidative activity of iron(III) complex of low molecular-weight polysaccharides were not less than that of low molecular-weight polysaccharides. [Copyright &y& Elsevier]

• Impaired interaction between prediction and sensory processes in schizophrenia. • Long-term regularity biases auditory perception in patients with auditory verbal hallucinations (AVHs). • Short-term repetition influences auditory perception more in patients without AVHs. • The impaired weighting between top-down predictions and bottom-up sensory processes can extend to tonal features. • Predictions at multiple timescales differentially modulate perception in schizophrenia. Cognitive models postulate that impaired source monitoring incorrectly weights the top-down prediction and bottom-up sensory processes and causes hallucinations. However, the underlying mechanisms of the interaction, such as whether the incorrectly weighting is ubiquitously on all levels of sensory features and whether different top-down processes have distinct effects in subgroups of schizophrenia are still unclear. This study investigates how multi-scale predictions influence perception of basic tonal features in schizophrenia. Sixty-three schizophrenia patients with and without symptoms of auditory verbal hallucinations (AVHs), and thirty healthy controls identified target tones in noise at the end of tone sequences. Predictions of different timescales were manipulated by either an alternating pattern in the preceding tone sequences (long-term regularity) or a repetition between the target tone and the tone immediately before (short-term repetition). The sensitivity index, d prime (d'), was obtained to assess the modulation of predictions on tone identification. Patients with AVHs showed higher d' when the target tones conformed to the long-term regularity of alternating pattern in the preceding tone sequence than when the target tones were inconsistent with the pattern. Whereas, the short-term repetition modulated the tone identification in patients without AVHs. Predictions did not influence tone identification in healthy controls. Our results suggest that impaired source monitoring in schizophrenia patients with AVHs heavily weights top-down predictions over bottom-up perceptual processes to form incorrect perception. The weighting function in source monitoring can extend to the processes of basic tonal features, and predictions at multiple timescales could differentially modulate perception in different clinical populations. The impaired interaction between top-down and bottom-up processes might underlie the development of hallucination symptoms in schizophrenia. [ABSTRACT FROM AUTHOR]

Simple Summary: Innate and acquired platinum resistance are the leading causes of epithelial ovarian cancer (EOC) mortality. However, the mechanisms remain elusive. Here we found that Exo70, a key subunit of the exocyst, is upregulated in EOC and promotes cisplatin efflux to facilitate innate resistance. More interestingly, cisplatin could downregulate Exo70 to sustain cell sensitivity. However, this function was hampered during prolonged cisplatin treatment, which in turn stabilized Exo70 to facilitate the acquired cisplatin resistance of EOC cells. Our study potentiates Exo70 as a promising target to overcome cisplatin resistance in EOC. Whilst researches elucidating a diversity of intracellular mechanisms, platinum-resistant epithelial ovarian cancer (EOC) remains a major challenge in the treatment of ovarian cancer. Here we report that Exo70, a key subunit of the exocyst complex, contributes to both innate and acquired cisplatin resistance of EOC. Upregulation of Exo70 is observed in EOC tissues and is related to platinum resistance and progression-free survival of EOC patients. Exo70 suppressed the cisplatin sensitivity of EOC cells through promoting exocytosis-mediated efflux of cisplatin. Moreover, cisplatin-induced autophagy-lysosomal degradation of Exo70 protein by modulating phosphorylation of AMPK and mTOR, thereby reducing the cellular resistance. However, the function was hampered during prolonged cisplatin treatment, which in turn stabilized Exo70 to facilitate the acquired cisplatin resistance of EOC cells. Knockdown of Exo70, or inhibiting exocytosis by Exo70 inhibitor Endosidin2, reversed the cisplatin resistance of EOC cells both in vitro and in vivo. Our results suggest that Exo70 overexpression and excessive stability contribute to innate and acquired cisplatin resistance through the increase in cisplatin efflux, and targeting Exo70 might be an approach to overcome cisplatin resistance in EOC treatment. [ABSTRACT FROM AUTHOR]

• A novel polysaccharide UPP was isolated from Ulva Pertusa. • The structural characterization of UPP was identified by NMR. • UPP was a semi-crystalline polymer without triple-helical structure. A new water-soluble polysaccharide UPP was obtained from Ulva Pertusa and its structure was studied. The structural analysis results showed that UPP was composed of eight residues. The bone structure of UPP was →4)-β-D-Xylp-(1→4)-α-L-Rhap3S(1→3,4)-β-L-Arap(1→3)-α-L-Rhap(1→2,4)-α-L-Rhap(1→4)-α-D-Galp(1→ and there were two main branches. The branch structure at the 3-position of 1,3,4-β-L-Arap was →3,4)-β-L-Arap(1→4)-β-D-Glcp3Me(1→4)- β-D-GlcpA(1→ and the branch structure at 2-position of 1,2,4-α-L-Rhap was →4)-β-D-GlcpA(1→4)-β-D-Xylp(1→. In addition, the physicochemical property analysis showed that UPP was a semi-crystalline polymer and there was no triple-helical structure. This structure analysis of UPP will be beneficial for future research on the algal polysaccharides. [ABSTRACT FROM AUTHOR]

Uranium high-efficiency separation from seawater still has some obstacles such as slow sorption rate, poor selectivity and biofouling. Herein, we report a strategy for ultrafast and highly selective uranium extraction from seawater by positively charged conjugated microporous polymers (CMPs). The polymers are synthesized by Sonogashira-Hagihara cross-coupling reaction of 1,3-dibromo-5,5-dimethylhydantoin and 1,3,5-triethynylbenzene, and then modified with oxime and carboxyl via click reaction. The CMPs show an ultrafast sorption (0.46 mg g−1 day−1) for uranium, and possess an outstanding selectivity with a high sorption capacity ratio of U/V (8.4) in real seawater. The study of adsorption process and mechanism indicate that the CMPs skeleton exhibits high affinity for uranium and can accelerate the sorption, and uranium(VI) is adsorbed on the materials by the interaction of oxime/carboxyl ligands and hydantoin. Moreover, the material can be simply loaded onto the filter membrane, and shows remarkable antibiofouling properties against E. coli and S. aureus and excellent uptake capacity for uranium with low concentration in real seawater. This work may provide a promising approach to design adsorbents with fast adsorption rate, high selectivity and antibacterial activity, and expand the thinking over the development of novel and highly efficient adsorbents for uranium extraction from seawater. Image 1 • A strategy is developed for highly efficient uranium extraction from seawater by CMPs. • The CMPs show an ultrafast sorption (0.46 mg g−1 day−1) for uranium in real seawater. • The CMPs possess an outstanding selectivity for uranium against vanadium (U/V = 8.4). • The CMPs have good antibiofouling properties against E. coli and S. aureus. • The CMPs can be bound onto microfiltration membrane for practical uranium adsorption. [ABSTRACT FROM AUTHOR]

Lactoferrin as a key basic protein in bovine milk has attracted extensive attentions due to its multifunctional activities. Thermal treatment has been widely used during processing of dairy products, which might damage the bioactivity of heat‐sensitive proteins. However, there has been little information on effect of heat treatment on the bioactivity of lactoferrin. In this study, the effects of four different thermal treatments (65°C/30 min, 72°C/10 s, 85°C/10 min, and 95°C/10 min) on lactoferrin were examined by sodium dodecyl sulfate–polyacrylamide gel electrophoresis, circular dichroism spectrum, electron microscope, dynamic light scattering, and semiquantitative RT‐PCR. Results revealed that these treatments altered its second structure and surface hydrophobicity. Moreover, the osteogenic activity of lactoferrin decreased by analyzing the effect of different samples on the mitogen‐activated protein kinase mRNA expression. These findings provided theory data for the research and development of lactoferrin as a functional component in food industry. Practical applications: As we know, thermal treatment has been widely used during processing of dairy products. Lactoferrin is a key basic protein component in bovine milk and has a variety of biological activities such as osteogenic activity. However, very few studies have focused on the effect of heat treatment on the osteogenic activity of lactoferrin, thereby limiting its applications. The objective of the present study was to investigate the effects of heating on the structure and osteogenic activity of lactoferrin. Results showed that the regular heat‐processing parameters in dairy industry and structural change of lactoferrin led to the loss of its osteogenic activity. These results will provide some theoretical and practical data for the development of lactoferrin as ingredient in functional food industry. [ABSTRACT FROM AUTHOR]

The immune system is very sensitive to radiation. This study revealed that adenosine 5′-monophosphate (5′-AMP) increased the DNA contents of the spleen and the spleen index of irradiated mice. Moreover, the exogenous 5′-AMP could significantly repair the ultra-structure of the damaged spleen through transmission electron microscopy. When indicators of the mouse immune system were assessed, the flow cytometry and enzyme-linked immunosorbent assay (ELISA) revealed that the administration of exogenous 5′-AMP could reduce the apoptosis in the splenic cells. It could also regulate the transition of cells towards S phase, increase the proportion of CD4+ and CD8+ cellular subsets, and enhance the secretion of interleukin-2 (IL-2), IL-4, IL-10, and interferon-γ (IFN-γ). These effects were associated with a decrease in oxidative stress, as evidenced by changes in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), reduced glutathione (GSH), and malondialdehyde (MDA) levels of spleen tissues. These results suggested that exogenous 5′-AMP could repair the damaged spleen, increase the spleen index, and regulate the cell cycles and apoptosis. There was an increase in the production of various cytokines and play a protective role on the immune system of irradiated mice by dynamically adjusting the REDOX balance. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction has been widely reported in psychiatric and neurodegenerative diseases. We aimed to investigate the association between matrilineal structures of Han Chinese populations and Alzheimer's disease (AD) by a 2-stage case-control study: A total of 341 AD patients and 435 normal individuals from Southwest China were analyzed for mitochondrial DNA sequence variations and were classified into respective haplogroups. A total of 371 AD patients and 470 normal individuals from East China, as validation samples, were genotyped for the variants defining the risk haplogroup. Haplogroup B5 had a significantly higher frequency in AD patients (7.33%) than in control subjects (3.68%) from Southwest China, and we found a similar pattern of higher frequency of B5 in patients in the case-control sample from East China. In the combined population, association of haplogroup B5 with AD risk was strengthened ( p = 0.02; odds ratio = 1.74; 95% confidence interval = 1.10–2.76). In lymphoblastoid cell lines belonging to haplogroup B5a, we observed significantly increased reactive oxygen species and decreased mitochondrial mass. Hela cells with stable expression of the MT-ATP6 gene with B5-defining variant m.8584G>A also showed a significantly decreased mitochondrial function. Taken together, our results indicated that haplogroup B5 conferred genetic susceptibility to AD in Han Chinese, and this effect was most likely mediated by ancient variant m.8584G>A. The predisposing effect of B5 to AD is consistent with the ancestral-susceptibility model of complex diseases. [ABSTRACT FROM AUTHOR]

Abstract: The leucine-rich repeat kinase–2 (LRRK2) gene has been regarded as 1 of the most common genetic causes of Parkinson's disease (PD). We hypothesized that LRRK2-susceptible allele(s) for PD might pose a risk for Alzheimer's disease (AD). In this study, we screened 12 LRRK2 gene variants in 2 independent cohorts from southwestern China (341 AD patients and 435 normal individuals) and eastern China (297 AD patients and 384 normal individuals), to discern the potential association between this gene and AD. No variant was identified to be associated with AD in either case-control sample. As both of the cohorts were of Han Chinese origin, we combined the LRRK2 variant data for the 2 sample sets together (a total of 638 AD patients and 819 normal individuals) and still found no association between the LRRK2 gene and AD, suggesting that LRRK2 gene variants may not affect the development of AD in Han Chinese individuals. [Copyright &y& Elsevier]