Double-strand-break repair protein rad21 homolog/Synaptotagmin-7 alleviates Alzheimer's disease in mice by promoting M2 polarization of microglia.

Synaptotagmin-7 (SYT7) has been proposed as an innovative therapeutic strategy for treating cognitive impairment, while its contribution to Alzheimer's disease (AD) alleviation remains unclear. In this study, we investigated the role and potential mechanisms of SYT7 in AD. APP/PS1 mice were induced as an AD mouse model, and RNA-sequencing was conducted to analyze the transcriptomic differences between the brain tissues of AD mice and controls. SYT7, which was the most significantly differentially expressed gene in the RNA-sequencing, was found to be reduced in AD-like mice, and overexpression of SYT7 alleviated cognitive dysfunction and attenuated neuroinflammation and neuronal loss in the hippocampal tissues of mice with AD. Transcription factor double-strand-break repair protein rad21 homolog (RAD21) bound to the promoter of SYT7 to activate SYT7 transcription. SYT7 and RAD21 were expressed in microglia. SYT7 and RAD21 both promoted M2 polarization of microglia, while silencing of SYT7 repressed the M2 polarization of microglia in the presence of RAD21 overexpression. Overall, our results indicate that RAD21 mediated transcriptional activation of SYT7 to promote M2 polarization of microglia, thereby alleviating AD-like symptoms in mice, which might provide prospective cues for developing therapeutic strategies to improve cognitive impairment and AD course.

Association between cheese and fish consumption and the occurrence of depression based on European population: mediating role of metabolites.

Background: The consumption of cheese and fish has been linked to the onset of depression. However, the connection between consuming cheese, consuming fish, experiencing depression, and the pathways that mediate this relationship remains unclear. The purpose of this research was to investigate the potential association between the consumption of cheese and fish and the occurrence of depression. Moreover, it is important to identify any metabolites that might be involved and understand their respective roles and functions. Methods: A two-step, two-sample Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) data on cheese, non-oily fish, and oily fish consumption and depression, along with 12 alternate mediators. The study included a total of 451,486 participants in the cheese consumption group, 460,880 in the non-oily fish consumption group, 460,443 in the oily fish consumption group, and 322,580 with a diagnosis of depression. The single nucleotide polymorphism (SNP) estimates were pooled using inverse-variance weighted, weighted median, MR-Egger, simple mode, and weighted mode. Results: The data we collected suggested that consuming more cheese correlated with a lower likelihood of experiencing depression (OR: 0.95; 95% CI: 0.92 to 0.98). Neither non-oily fish nor oily fish consumption was directly linked to depression onset (p = 0.08, p = 0.78, respectively). Although there was a direct causal relationship with depression, the mediating relationship of triglycerides (TG), total cholesterol in large HDL, cholesterol to total lipids ratio in large HDL, free cholesterol to total lipids ratio in large HDL, glycine, and phospholipids to total lipids ratio in very large HDL of cheese intake on depression risk were - 0.002 (95% CI: -0.023 - 0.020), -0.002 (95% CI: -0.049 - 0.045), -0.001 (95% CI: -0.033 - 0.031), -0.001 (95% CI: -0.018 - 0.015), 0.001 (95% CI: -0.035 - 0.037), and - 0.001 (95% CI: -0.024 - 0.021), respectively. The mediating relationship of uridine, free cholesterol to total lipids ratio in large HDL, total cholesterol in large HDL, acetoacetate, and 3-hydroxybutyrate (3-HB) between non-oily fish consumption and depression risk were 0.016 (95% CI: -0.008 - 0.040), 0.011 (95% CI: -1.269 - 1.290), 0.010 (95% CI: -1.316 - 1.335), 0.011 (95% CI: -0.089 - 0.110), and 0.008 (95% CI: -0.051 - 0.068), respectively. The mediation effect of uridine and free cholesterol to total lipids ratio in large HDL between intake of oily fish and the risk of depression was found to be 0.006 (95% CI: -0.015 - 0.028) and - 0.002 (95% CI: -0.020 - 0.017), respectively. The correlation between eating cheese and experiencing depression persisted even when adjusting for other variables like Indian snacks, mango consumption, sushi consumption, and unsalted peanuts using multivariable MR. Conclusion: The consumption of cheese and fish influenced the likelihood of experiencing depression, and this may be mediated by certain metabolites in the body. Our study provided a new perspective on the clinical treatment of depression.

Using intravoxel incoherent motion imaging to evaluate uric acid-induced renal injury and efficacy after treatment.

OBJECTIVES: To validate the feasibility of intravoxel incoherent motion imaging (IVIM) for monitoring renal injury and uric acid-lowering efficacy in a rat model of hyperuricaemia. METHODS: A total of 92 rats were analysed and categorized into 4 groups: control (CON), hyperuricaemia (HUA), allopurinol intervention (ALL), and combined intervention (COM). Eight rats were randomly selected from each group and underwent IVIM scanning on days 0, 1, 3, 5, 7, and 9. Quantitative magnetic resonance values (D, D*, and f values) measured from the different renal anatomical regions. Quantitative histopathological analysis was performed to assess renal tubular injury using neutrophil gelatinase-associated lipocalin (NGAL), and renal fibrosis using alpha-smooth-muscle-actin (α-SMA). Pearson's correlation analysis was used to determine the correlation between IVIM-derived parameters and the expression of NGAL and α-SMA. RESULTS: The D values of the HUA, ALL, and COM groups generally showed a downward trend over time, and this fluctuation was most significant in the HUA group. The D values showed significant intergroup differences at each point, whereas only a few discrepancies were found in the D* and f values. In addition, the renal D value was negatively correlated with the positive staining rates for NGAL and α-SMA (P < .05), except for the lack of correlation between Dos and α-SMA (P > .05). CONCLUSION: IVIM could be a noninvasive and potential assessment modality for the evaluation of renal injury induced by hyperuricaemia and its prognostic efficacy. ADVANCES IN KNOWLEDGE: IVIM could be a surrogate manner in monitoring renal damage induced by hyperuricaemia and its treatment evaluation.

Temporal dynamic changes of intrinsic brain activity in Alzheimer's disease and mild cognitive impairment patients: a resting-state functional magnetic resonance imaging study.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory impairment. Previous studies have largely focused on alterations of static brain activity occurring in patients with AD. Few studies to date have explored the characteristics of dynamic brain activity in cognitive impairment, and their predictive ability in AD patients. METHODS: One hundred and eleven AD patients, 29 MCI patients, and 73 healthy controls (HC) were recruited. The dynamic amplitude of low-frequency fluctuation (dALFF) and the dynamic fraction amplitude of low-frequency fluctuation (dfALFF) were used to assess the temporal variability of local brain activity in patients with AD or mild cognitive impairment (MCI). Pearson's correlation coefficients were calculated between the metrics and subjects' behavioral scores. RESULTS: The results of analysis of variance indicated that the AD, MCI, and HC groups showed significant variability of dALFF in the cerebellar posterior and middle temporal lobes. In AD patients, these brain regions had high dALFF variability. Significant dfALFF variability was found between the three groups in the left calcarine cortex and white matter. The AD group showed lower dfALFF than the MCI group in the left calcarine cortex. CONCLUSIONS: Compared to HC, AD patients were found to have increased dALFF variability in the cerebellar posterior and temporal lobes. This abnormal pattern may diminish the capacity of the cerebellum and temporal lobes to participate in the cerebrocerebellar circuits and default mode network (DMN), which regulate cognition and emotion in AD. The findings above indicate that the analysis of dALFF and dfALFF based on functional magnetic resonance imaging data may give a new insight into the neurophysiological mechanisms of AD.

EEG power spectral analysis reveals tandospirone improves anxiety symptoms in patients with Alzheimer's disease: a prospective cohort study.

BACKGROUND: To study the efficacy of tandospirone citrate in treating Alzheimer's disease (AD) patients with anxiety. METHODS: Thirty mild-to-moderate AD patients with anxiety symptoms were randomly divided into a monotherapy group (donepezil) and a combination therapy group (donepezil and tandospirone). The treatment lasted for 12 weeks. Drug efficacy was regularly assessed using psychological assessment scales and quantitative pharmaco-electroencephalogram (QPEEG) power spectral analysis. RESULTS: After 12 weeks of treatment, the mean Hamilton Anxiety Scale (HAMA) score and mean Neuropsychiatric Inventory (NPI) score of the combination therapy group were 5.13±4.18 and 4.2±5.0, respectively, which was significantly lower compared to baseline and the monotherapy group (all P<0.05). The mean attention score on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) was 0.07±0.26 for the combination group, which was significantly lower than that of the monotherapy group (P<0.05). QPEEG revealed that the power values of the δ wave in the right prefrontal lobe, left middle temporal lobe and right posterior temporal lobe decreased in the combination therapy group but not in the monotherapy group. Similarly, the power values of the α2 wave in the right parietal, right posterior temporal and left middle temporal lobes, and the ß1 wave power values of left middle temporal and left posterior temporal lobes were also significantly decreased in the combination therapy group, but not in the monotherapy group. CONCLUSIONS: Tandospirone citrate can significantly improve anxiety symptoms and attention in patients with mild to moderate AD. QPEEG examination might provide a objective way for the efficacy of the tandospirone in anxiety symptoms of the patients with Alzheimer's disease.

Disrupted balance of long and short-range functional connectivity density in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients: a resting-state fMRI study.

BACKGROUND: Alzheimer's disease (AD) is an age-progressive neurodegenerative disorder that affects cognitive function. There have been several functional connectivity (FC) strengths; however, FC density needs more development in AD. Therefore, this study wanted to determine the alternations in resting-state functional connectivity density (FCD) induced by Alzheimer's and mild cognitive impairment (MCI). METHODS: One hundred and eleven AD patients, 29 MCI patients, and 73 healthy controls (age- and sex-matched) were recruited and assessed using resting-state functional magnetic resonance imaging (MRI) scanning. The ultra-fast graph theory called FCD mapping was used to calculate the voxel-wise short- and long-range FCD values of the brain. We performed voxel-based between-group comparisons of FCD values to show the cerebral regions with significant FCD alterations. We performed Pearson's correlation analyses between aberrant functional connectivity densities and several clinical variables with adjustment for age and sex. RESULTS: Patients with cognition decline showed significantly abnormal long-range FCD in the cerebellum crus I, right insula, left inferior frontal gyrus, left superior frontal gyrus, left inferior frontal gyrus, and right middle frontal gyrus. The short-range FCD changed in the cerebellum crus I, left inferior frontal gyrus, left superior occipital gyrus, and right middle frontal gyrus. The long- and short-range functional connectivity in the left inferior frontal gyrus was positively correlated with Mini-mental State Examination (MMSE) scores. CONCLUSIONS: FCD in the identified regions reflects mechanism and compensation for loss of cognitive function. These findings could improve the pathology of AD and MCI and supply a neuroimaging marker for AD and MCI.

Biomimetic composite scaffolds based on surface modification of polydopamine on ultrasonication induced cellulose nanofibrils (CNF) adsorbing onto electrospun thermoplastic polyurethane (TPU) nanofibers.

To improve the interaction between cells and scaffolds, the appropriate surface chemical property is very important for tissue engineering scaffolds. In this study, the thermoplastic polyurethane (TPU) nanofibers was firstly fabricated by electrospinning technique, and then its surface was modified with cellulose nanofibrils (CNF) particles by ultrasonic-assisted to obtain TPU/CNF nanofibers. Subsequently, the TPU/CNF-polydopamine (PDA) composite nanofibers with core/shell structure were fabricated by PDA coating method. In comparison with TPU nanofibers, the uniformization of PDA coating layer on the surface of TPU/CNF composite nanofibers significantly increased due to the addition of CNF, which used as the active sites to guide the PDA particles accumulated along with the fiber direction. The water absorption and hydrophilicity of TPU/CNF-PDA composite nanofibers were significantly increased in comparison with those of TPU and TPU/CNF nanofibers. The mechanical properties of the TPU/CNF-PDA composite nanofibers were higher than those of the TPU and TPU/CNF nanofibers due to the formation of strong hydrogen bonds between PDA and TPU/CNF, making TPU, CNF and PDA strongly adhere to each other. The attachment and viability of mouse embryonic osteoblasts cells (MC3T3-E1) cultured on TPU/CNF-PDA composite nanofibers were obviously enhanced compared with TPU and TPU/CNF nanofibers. Those results suggested that the modified TPU/CNF-PDA composite nanofibers have excellent mechanical and biological properties, which promoting them potentially useful for tissue engineering scaffolds. The presented strategy represents a general route to modify the surface of scaffolds, which are promising for tissue engineering applications.

Dual super-amphiphilic modified cellulose acetate nanofiber membranes with highly efficient oil/water separation and excellent antifouling properties.

Along with increasing oily, industrial wastewater and seawater pollution, oil spills-and their clean-up via the separation of oil and water-are still a worldwide challenge. Aiming to fabricate an oil/water separation membrane with excellent comprehensive performance, we report here a new type of multifunctional deacetylated cellulose acetate (d-CA) membrane. The cellulose acetate (CA) nanofiber membranes are fabricated by electrospinning and then deacetylated to obtain the d-CA nanofiber membranes, which are super-amphiphilic in air, oleophobic in water, and super-hydrophilic in oil. The multifunctional d-CA nanofiber membranes can be used as water-removal substances for oil/water mixtures, as well as emulsified oil/water and oil/corrosive aqueous systems, with gravity as the only needed driving force. The d-CA nanofiber membranes possess the highest separation flux, reaching up to 38,000 L/m2·h, and the highest separation efficiency, reaching up to 99.97 % for chloroform/water mixtures under the force of gravity. In fact, the separation flux was several times higher than that of commercial CA (c-CA) membranes. The excellent anti-pollution and self-cleaning abilities endow the membranes with powerful cyclic stability and reusability. The d-CA nanofiber membranes show great application prospects in chemical plants, textile mills, and the food industry, as well as offshore oil spills, to separate oil from water.

Clinicopathologic and prognostic significance of human epidermal growth factor receptor in patients with gastric cancer: An updated meta-analysis.

PURPOSE: The aim of this update meta-analysis was to clarify the clinicopathologic and prognostic significance of human epidermal growth factor receptor(EGFR) expression in gastric cancer patients. EXPERIMENTAL DESIGN: Several electronic databases were searched from January 1970 to May 2016. The odds ratio (OR) was calculated to assess the association between EGFR expression and pathological parameters. The hazard ratio (HR) and 95% CI were calculated to explore the relationship between EGFR expression and overall survival. RESULTS: Finally 7229 patients with gastric cancer from 25 eligible studies were included in the present meta analysis. High EGFR expression was found to be significantly related with tumor differentiation (OR=1.96, 95%CI: 1.14-3.34, Z=2.43, P=0.015), lymph node metastasis (OR=2.20, 95% CI: 1.63-2.96, Z=5.17, P=0.001), and tumor stage (OR=2.13, 95% CI: 1.35-3.36, Z=3.25, P=0.001). However, high EGFR expression was not significantly associated with invasion depth (OR=2.09, 95% CI: 0.4-11.05, Z=0.87, P=0.385). The pooled HR suggested that high EGFR expression was significantly correlated with overall survival (HR=1.19, 95% CI 1.04-1.37, Z=2.44, P=0.015). CONCLUSIONS: The present meta-analysis demonstrated that high EGFR expression significantly predicts poor prognosis, suggesting that high EGFR expression may serve as a predictive biomarker for poor prognosis in patients with gastric cancer.