Publications by authors named "Yushan Wang"

73 Publications

Application of a new percutaneous multi-function pedicle locator in minimally invasive spine surgery.

Sci Rep 2021 Nov 2;11(1):21451. Epub 2021 Nov 2.

Department of Orthopedics, Jinzhou Central Hospital, Jinzhou, 121001, Liaoning, People's Republic of China.

In this study, a new percutaneous multi-function pedicle locator was designed for personalized three-dimensional positioning of a pedicle in minimally invasive spine surgery (MISS) without computer-assisted navigation technology. The proposed locator was used in a number of patients during MISS, and its advantages were analyzed. Based on the position of a pedicle determined by computed tomography (CT) and fluoroscopic images of a patient, 6 lines and 2 distances were used to determine the puncture point of a pedicle screw on skin, while 2 angles were used to indicate the direction of insertion of a pedicle guide needle from the patient's body surface. The results of the proposed locator were compared with those of the conventional freehand technique in MISS. The potential benefits of using the locator included enhanced surgical accuracy, reduced operation time, alleviation of the harmful intra-operative radiation exposure, lower costs, and shortened learning curve for young orthopedists.
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http://dx.doi.org/10.1038/s41598-021-01027-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563717PMC
November 2021

Acute and long-term effects of VX in rat brain cell aggregate culture.

Toxicol In Vitro 2021 Oct 12;78:105256. Epub 2021 Oct 12.

Defence Research & Development Canada, Suffield Research Centre, Box 4000, Medicine Hat, Alberta T1A 8K6, Canada.

The contact poison VX (O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate) is a chemical warfare agent that is one of the most toxic organophosphorus compounds known. Its primary mechanism of toxic action is through the inhibition of acetylcholinesterase and resultant respiratory paralysis. The majority of work on VX has thus concentrated on its potent anticholinesterase activity and acute toxicity, with few studies investigating potential long-term effects. In this report we describe the effects of VX in aggregating rat brain cell cultures out to 28 days post-exposure. Cholinesterase activity was rapidly inhibited (60 min IC = 0.73 +/- 0.27 nM), but recovered towards baseline values over the next four weeks. Apoptotic cell death, as measured using caspase-3 activity was evident only at 100 μM concentrations. Cell type specific enzymatic markers (glutamine synthase, choline acetyltransferase and 2',3'-cyclic nucleotide 3'-phosphodiesterase) showed no significant changes. Total Akt levels were unchanged, while an increased phosphorylation of this protein was noted only at the highest VX concentration on the first day post-exposure. In contrast, significant and delayed (28 days post-exposure) decreases were noted in vascular endothelial growth factor (VEGF) levels, a protein whose reduced levels are known to contribute to neurodegenerative disorders. These observations may indicate that the long-term effects noted in some survivors of nerve agent intoxication may be due to VX-induced declines in brain VEGF levels.
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http://dx.doi.org/10.1016/j.tiv.2021.105256DOI Listing
October 2021

The Effect and Mechanism of Cholesterol and Vitamin B on Multi-Domain Cognitive Function: A Prospective Study on Chinese Middle-Aged and Older Adults.

Front Aging Neurosci 2021 27;13:707958. Epub 2021 Aug 27.

School of Public Health, Capital Medical University, Beijing, China.

Nutrients are associated with cognitive function, but limited research studies have systematically evaluated on multi-domain cognitive function. The aim of this study was to investigate the effect and mechanism of specific nutrient on multi-domain cognitive function, and provide nutrition guidance for improving cognitive function. Participants were selected based on a multicenter prospective study on middle-aged and older adults in China. Global cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Nutrients intake was assessed according to food frequency questionnaire and China Food Composition Database, and principal component analysis was performed to extract nutrient patterns. Associations between specific nutrients and cognitive function were assessed using log-binomial regression. Restricted cubic spline was used to illustrate the dose-response relationship of nutrients with multi-domain cognitive function. Mediation analysis was used to determine the mechanism of nutrients in cognitive function. Four nutrient patterns were identified (vitamin-mineral, protein-carbohydrate, fatty acid-vitamin E, and cholesterol-vitamin B), and only a nutrient pattern rich in cholesterol and vitamin B was found associated with cognitive function (RR = 0.891, 95%CI = 0.794-0.999). In multi-domain cognitive function, dietary cholesterol and vitamin B were related to better performance of visual memory function ( = 0.034, = 0.02). In dose-response relationship, it suggested a U-shaped association between vitamin B and MMSE ( = 0.02) within a certain range. Dietary intake rich in cholesterol and vitamin B was associated with better cognitive function, and vitamin B had a U-shaped dose-response relation with MMSE. Thus, ensuring moderate cholesterol and vitamin Bintake may be an advisable strategy to improve cognitive function in middle-aged and older adults. EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610.
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http://dx.doi.org/10.3389/fnagi.2021.707958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430239PMC
August 2021

Vitamin D Deficiency Is Associated with Disrupted Cholesterol Homeostasis in Patients with Mild Cognitive Impairment.

J Nutr 2021 Sep 11. Epub 2021 Sep 11.

School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China Capital Medical University, You An Men Wai, Beijing, China.

Background: Several studies have reported that dietary and serum concentrations of vitamin D and cholesterol are correlated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, little is known about whether 25 hydroxyvitamin D [25(OH)D], lipids, and oxysterols are related to cognitive function.

Objective: This study sought to explore the relations between 25(OH)D, lipids, oxysterols, and cognitive function.

Methods: In this study, about 209 MCI patients and 209 age- and gender-matched healthy controls were recruited from the Shanxi province of China (49.5% male; median [IQR] age: 63 [59-66] y). Serum concentrations of 25(OH)D, lipids, and oxysterols were measured using ultra-performance LC-MS. Cognitive performance was determined via comprehensive mental, verbal, and auditory cognitive tests. Dietary information was collected using a semiquantitative FFQ and 3 consecutive days of 24-h dietary recalls. Logistic regression analyses, Spearman's correlation, and partial correlation analyses were used to explore correlation between the variables.

Results: Participants with vitamin D deficiency [serum 25(OH)D <20.0 ng/mL] were 3 times more likely to develop MCI compared to those with adequate vitamin D (≥30 ng/mL) concentrations. The AUC of 25(OH)D was 0.72 and the cut-off was 16.5 ng/mL (sensitivity:  50.3%,  specificity: 84.4%). Serum 25(OH)D concentrations were negatively correlated with total cholesterol (TC) (r = -0.19, P = 0.02), LDL-cholesterol (r = -0.17, P = 0.04), and 24S,25-epoxycholesterol (24S,25-epoxy-CHO) (r = -0.21, P = 0.01). Conversely, the Montreal Cognitive Assessment (MoCA) (r = 0.185, P < 0.001) and symbol digit modalities test (SDMT) (r = 0.11, P = 0.03) scores were positively correlated with serum 25(OH)D concentrations.

Conclusion: The study identified significant differences in serum 25(OH)D concentrations between MCI patients and cognitive healthy controls, and there was a correlation between serum concentrations of 25(OH)D, lipids, and oxysterols and cognitive impairment among people. This study was registered at the Chinese Clinical Trial Registry as ChiCTR1900025452.
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http://dx.doi.org/10.1093/jn/nxab296DOI Listing
September 2021

Management of the Cavity After Removal of Giant Cell Tumor of the Bone.

Front Surg 2021 29;8:626272. Epub 2021 Jul 29.

Orthopedics Department, Second Hospital of Shanxi Medical University, Taiyuan, China.

To find out the most appropriate management scheme through the analysis and comparison of different inactivation methods and filling materials. A systematic literature search was performed using the terms, anhydrous ethanol, phenol, hypertonic saline, cryotherapy, thermal therapy, bone reconstruction, GCTB, and etc., Selected articles were studied and summarized. The mechanism, clinical effects, and influence on bone repair of various methods are presented. Recent developments and perspectives are also demonstrated. Compared to curettage alone, management of the residual cavity can effectively reduce the recurrence of giant cell tumours of bone. It is a complex and multidisciplinary process that includes three steps: local control, cavity filling, and osteogenic induction. In terms of local control, High-speed burring can enlarge the area of curettage but may cause the spread and planting of tumour tissues. Among the inactivation methods, Anhydrous ethanol, and hyperthermia therapy are relatively safe and efficient. The combination of the two may achieve a better inactivation effect. When inactivating the cavity, we need to adjust the approach according to the invasion of the tumour. Filling materials and bone repair should also be considered in management.
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http://dx.doi.org/10.3389/fsurg.2021.626272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358324PMC
July 2021

Nomogram Model for Screening the Risk of Type II Diabetes in Western Xinjiang, China.

Diabetes Metab Syndr Obes 2021 7;14:3541-3553. Epub 2021 Aug 7.

Center of Health Management, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, People's Republic of China.

Objective: A simple type 2 diabetes mellitus (T2DM) screening model was established preciously based on easily available variables for identifying high-risk individuals in western Xinjiang, China.

Methods: A total of 458,153 cases participating in the national health examination were recruited. Logistic regression and the least absolute shrinkage and selection operator (LASSO) models were used for univariate analysis, factors selection, and the establishment of prediction model. Receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test and clinical decision curve (CDA) were applied for evaluating the discrimination, calibration and clinical validity, respectively. The optimal threshold for predicting risk factors for T2DM has been estimated as well.

Results: The nomogram depicted the risk of T2DM based on different genders, the factors mainly consisted of age, family history of T2DM (FHOT), waist circumference (WC), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDLc), body mass index (BMI), high-density lipoprotein cholesterol (HDLc), etc. The area under ROC of men and women was 0.864 and 0.816 in the development group, similarly in the validation group, which was 0.865 and 0.815, respectively. The calibration curve showed that the nomogram was accurate for predicting the risk of T2DM, and the CDA proved great clinical application value of the nomogram. Threshold values of the age, WC, TC, TG, HDLc, BMI in different genders were 52.5 years old (men) and 48.5 years old (women), 85.50 cm (men) and 89.9 cm (women), 4.94 mmol/L (men) and 4.94mmol/L (women), 1.26mmol/L (men) and 1.67mmol/L (women), 1.40mmol/L (men) and 1.40mmol/L (women), 24.70kg/m (men) and 24.95kg/m (women), respectively.

Conclusion: Our results give a clue that the nomogram may be useful for identifying adults who have high risk for diabetes, which is simple, affordable, with high credibility and can be widely implemented. Further studies are needed to evaluate the utility and feasibility of this model in various settings.
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http://dx.doi.org/10.2147/DMSO.S313838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357405PMC
August 2021

Can Kinesio taping improve discomfort after mandibular third molar surgery? A systematic review and meta-analysis.

Clin Oral Investig 2021 Sep 23;25(9):5139-5148. Epub 2021 Jul 23.

Department of Orthodontics, Ningbo Stomatology Hospital, 315000, Ningbo, China.

Objective: The purpose of this study was to evaluate whether Kinesio taping (KT) can improve patient discomfort after mandibular third molar surgery.

Materials And Methods: This systematic review and meta-analysis was conducted according to the PICO strategy. We searched 4 databases for related articles. All controlled trials or randomized controlled trials that evaluated the application of KT after mandibular third molar surgery were included. Screening and article selection were carried out by two independent reviewers. The main evaluation indicators were facial swelling, pain, and trismus. All statistical analyses were conducted using Review Manager 5.3 software.

Result: This analysis included 8 articles. The combined results showed that compared with the control group, the postoperative application of KT significantly reduced pain in the early (early stage mean difference (MD), - 2.00; 95% confidence interval (CI), - 2.40 to - 1.60; P < 0.00001) and late (late stage MD, - 1.18; 95% CI, - 2.26 to - 0.11; P = 0.03) postoperative periods and, thus, reduced the intake of painkillers. KT also reduced facial swelling in the early and late postoperative periods (early stage standardized mean difference (SMD), - 1.34; 95% CI, - 1.99 to - 0.68; P < 0.0001; late stage SMD, - 0.31; 95% CI, - 0.51 to - 0.11; P = 0.002). In addition, the postoperative application of KT improved restricted mouth opening in the early and late postoperative periods (early stage MD, - 5.03 mm; 95% CI, - 6.32 to - 3.74 mm; P < 0.00001; late stage MD, - 3.42 mm; 95% CI, - 5.31 to - 1.52 mm; P = 0.0004).

Conclusion: KT can significantly reduce postoperative pain, swelling, and trismus after impacted mandibular tooth extraction. Additional high-quality and rigorously designed randomized controlled trials should be conducted to verify these conclusions.

Clinical Relevance: KT is a low-cost, simple, effective nondrug therapy for the postoperative management of mandibular third molar extraction and has broad prospects for clinical application.
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http://dx.doi.org/10.1007/s00784-021-04069-2DOI Listing
September 2021

Optics metrology and at-wavelength wavefront characterization by a microfocus X-ray grating interferometer.

Opt Express 2021 Jul;29(14):22704-22713

A microfocus X-ray grating interferometer (MFXGI) is proposed to measure the profile of the X-ray wavefront and slope error of X-ray optical elements. This device consists of a phase grating G to modulate the incoming wavefront and an absorption grating G as a transmission mask for the position-sensitive detector. The wavefront distortions caused by the deformable mirror were analyzed under operating conditions for in situ investigation of X-ray optical elements. The MFXGI can obtain direct and reflected beams in one recorded image at the same time through a microfocus X-ray source. The direct beam can be used to calculate the parameter errors and spherical shape for error compensation and retrieve the aspherical shape of the height profile. This instrument is expected to be a valuable tool for further technical progress in X-ray adaptive optics and X-ray mirror manufacturing and mounting.
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http://dx.doi.org/10.1364/OE.430269DOI Listing
July 2021

Diet quality, gut microbiota, and microRNAs associated with mild cognitive impairment in middle-aged and elderly Chinese population.

Am J Clin Nutr 2021 08;114(2):429-440

School of Public Health, Capital Medical University, Beijing, China.

Background: Diet, the gut microbiota, and microRNAs (miRNAs) have been recognized as factors possibly influencing the pathogenesis of Alzheimer's disease. However, the combined role of diet, the gut microbiota, and miRNAs in mild cognitive impairment (MCI) has not been extensively investigated.

Objectives: To examine the associations among diet quality, the gut microbiota, miRNAs, and risks of MCI in middle-aged and elderly Chinese population.

Methods: Participants were drawn from the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer's disease (EMCOA) study. We included 2239 participants who completed comprehensive cognitive tests and dietary surveys at baseline and follow-up. Chinese Dietary Guidelines Index 2018 (CDGI-2018), Energy-Adjusted Dietary Inflammatory Index (E-DII) and Healthy Lifestyle Score (HLS) values were calculated based on data from a standard questionnaire. Changes of gut microbiota and serum miRNA expression were detected in 75 MCI and 52 healthy participants. The receiver operating characteristic curve was performed based on a logistic regression model distinguishing patients with MCI from healthy controls.

Results: Higher CDGI-2018 (RR, 0.75; 95% CI: 0.58-0.98) and HLS (RR, 0.54; 95% CI: 0.34-0.84) values and lower E-DII (RR, 1.46; 95% CI: 1.14-1.87) values were significantly associated with a lower risk of MCI. Lower microbial diversity and abundance of Faecalibacterium, unidentified Ruminococcaceae, and Alistipes were found in MCI participants compared with healthy controls. The abundance of ProteobacteriaandGammaproteobacteria was higher in MCI participants and was correlated with hsa-let-7g-5p, hsa-miR-107, and hsa-miR-186-3p. The predictive signatures of diet quality scores, differential gut microbiota, and serum miRNAs had good performance on distinguishing MCI participants from healthy individuals (AUC = 0.91).

Conclusions: A better diet quality is associated with a lower risk of MCI, which may be mediated by the microbiota composition and miRNA expression. These findings suggest that diet, the gut microbiota, and miRNAs may serve as a combinatorial biomarker to identify MCI patients and provide new insight for the diagnosis and prevention of MCI. This study was registered at the Chinese Clinical Trial Registry as ChiCTROOC-17011882.
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http://dx.doi.org/10.1093/ajcn/nqab078DOI Listing
August 2021

Sulphur mustard induces progressive toxicity and demyelination in brain cell aggregate culture.

Neurotoxicology 2021 05 19;84:114-124. Epub 2021 Mar 19.

Defence Research & Development Canada, Suffield Research Centre, Box 4000, Medicine Hat, Alberta, T1A 8K6, Canada.

Sulphur mustard (H; bis(2-chloroethyl) sulphide) is a vesicant chemical warfare (CW) agent that has been well documented as causing acute injury to the skin, eyes and respiratory system. Although a great deal of research effort has been expended to understand how H exerts these effects, its mechanism of action is still poorly understood. At high exposures, H also causes systemic toxicity with chronic and long-term effects to the immune, cardiovascular and central nervous systems, and these aspects of H poisoning are much less studied and comprehended. Rat aggregate cultures comprised of multiple brain cell types were exposed to H and followed for four weeks post-exposure to assess neurotoxicity. Toxicity (LDH, caspase-3 and aggregate diameter) was progressive with time post-exposure. In addition, statistically significant changes in neurofilament heavy chain (NFH), glial fibrillary acidic protein (GFAP), Akt phosphorylation, IL-6, GRO-KC and TNF-α were noted that were time- and concentration-dependent. Myelin basic protein, CNPase and vascular endothelial growth factor (VEGF) were found to be especially sensitive to H exposure in a time- and concentration-dependent fashion, with levels falling to ∼50 % of control values at ∼10 μM H by 8 days post-exposure. Demyelination and VEGF inhibition may be causal in the long-term neuropsychological illnesses that have been documented in casualties exposed to high concentrations of H, and may also play a role in the peripheral neuropathy that has been observed in some of these individuals.
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http://dx.doi.org/10.1016/j.neuro.2021.03.004DOI Listing
May 2021

Deep learning model for classifying endometrial lesions.

J Transl Med 2021 01 6;19(1):10. Epub 2021 Jan 6.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110021, People's Republic of China.

Background: Hysteroscopy is a commonly used technique for diagnosing endometrial lesions. It is essential to develop an objective model to aid clinicians in lesion diagnosis, as each type of lesion has a distinct treatment, and judgments of hysteroscopists are relatively subjective. This study constructs a convolutional neural network model that can automatically classify endometrial lesions using hysteroscopic images as input.

Methods: All histopathologically confirmed endometrial lesion images were obtained from the Shengjing Hospital of China Medical University, including endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyps, and submucous myomas. The study included 1851 images from 454 patients. After the images were preprocessed (histogram equalization, addition of noise, rotations, and flips), a training set of 6478 images was input into a tuned VGGNet-16 model; 250 images were used as the test set to evaluate the model's performance. Thereafter, we compared the model's results with the diagnosis of gynecologists.

Results: The overall accuracy of the VGGNet-16 model in classifying endometrial lesions is 80.8%. Its sensitivity to endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyp, and submucous myoma is 84.0%, 68.0%, 78.0%, 94.0%, and 80.0%, respectively; for these diagnoses, the model's specificity is 92.5%, 95.5%, 96.5%, 95.0%, and 96.5%, respectively. When classifying lesions as benign or as premalignant/malignant, the VGGNet-16 model's accuracy, sensitivity, and specificity are 90.8%, 83.0%, and 96.0%, respectively. The diagnostic performance of the VGGNet-16 model is slightly better than that of the three gynecologists in both classification tasks. With the aid of the model, the overall accuracy of the diagnosis of endometrial lesions by gynecologists can be improved.

Conclusions: The VGGNet-16 model performs well in classifying endometrial lesions from hysteroscopic images and can provide objective diagnostic evidence for hysteroscopists.
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http://dx.doi.org/10.1186/s12967-020-02660-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788977PMC
January 2021

The Prevalence, Risk Factors, and Outcomes of Sepsis in Critically Ill Patients in China: A Multicenter Prospective Cohort Study.

Front Med (Lausanne) 2020 17;7:593808. Epub 2020 Dec 17.

Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, Beijing, China.

Sepsis is a main cause of morbidity and mortality in critically ill patients. The epidemiology of sepsis in high-income countries is well-known, but information on sepsis in middle- or low-income countries is still deficient, especially in China. The purpose of this study was to explore the prevalence, characteristics, risk factors, treatment, and outcomes of sepsis in critically ill patients in tertiary hospitals in China. A multicenter prospective observational cohort study was performed with consecutively collected data from adults who stayed in any intensive care unit (ICU) for at least 24 h; data were collected from 1 January 2014 to 31 August 2015, and patients were followed until death or discharge from the hospital. A total of 4,910 patients were enrolled in the study. Of these, 2,086 (42.5%) presented with sepsis or septic shock on admission to the ICU or within the first 48 h after admission to the ICU. ICU mortality was higher in patients with sepsis (13.1%) and septic shock (39.0%) and varied according to geographical region. Acinetobacter, Pseudomonas, and Staphylococcus infections were associated with increased ICU mortality. In addition, age, Acute Physiology, and Chronic Health Evaluation II (APACHE II) scores, pre-existing cardiovascular diseases, malignant tumors, renal replacement therapy (RRT), and septic shock were independent risk factors for mortality in patients with sepsis. The prompt administration of antibiotics (OR 0.65, 95% CI 0.46-0.92) and 30 mL/kg of initial fluid resuscitation during the first 3 h (OR 0.43, 95% CI 0.30-0.63) improved the outcome in patients with septic shock. Sepsis was common and was associated with a high mortality rate in critically ill patients in tertiary hospitals in China. The prompt administration of antibiotics and 30 mL/kg fluid resuscitation decreased the risk of mortality.
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http://dx.doi.org/10.3389/fmed.2020.593808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774866PMC
December 2020

27-Hydroxycholesterol Promotes the Transfer of Astrocyte-Derived Cholesterol to Neurons in Co-cultured SH-SY5Y Cells and C6 Cells.

Front Cell Dev Biol 2020 24;8:580599. Epub 2020 Nov 24.

School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.

Abnormality in cholesterol homeostasis in the brain is a feature of Alzheimer's disease (AD). 27-Hydroxycholesterol (27-OHC) has been identified as a possible biomarker of AD, but its effects on cholesterol metabolism have not been fully characterized. This study was aimed to investigate the impacts of 27-OHC on cholesterol metabolism in nerve cells. SH-SY5Y cells and C6 cells were co-cultured and treated with 5, 10, and 20 μM 27-OHC for 24 h. Results showed that 27-OHC decreased cholesterol levels and up-regulated the expression of transport-related proteins in C6 cells. In SH-SY5Y cells, 27-OHC increased cholesterol accumulation, especially on plasma membrane (PM), which was consistent with the up-regulation of expressions of cholesterol endocytosis receptors, lipid raft-related proteins, and cholesterol esterase. Simultaneously, accumulation of membrane cholesterol promoted cholesterol conversion to 24S-OHC by CYP46A1(24S-hydroxylase) transfer from the endoplasmic reticulum (ER) to PM. Besides, Aβ levels were elevated in SH-SY5Y cells after 27-OHC treatment. Our results suggest that 27-OHC motivates the transfer of astrocyte-derived cholesterol to neurons. Although there exists a feedback mechanism that excessive cholesterol promotes its conversion to 24S-OHC, the increased cholesterol induced by 27-OHC could not be wholly offset in neurons.
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http://dx.doi.org/10.3389/fcell.2020.580599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732486PMC
November 2020

Bioinformatics Identification of the Expression and Clinical Significance of E2F Family in Endometrial Cancer.

Front Genet 2020 4;11:557188. Epub 2020 Nov 4.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Background: Besides being one of the most prevalent cancers among women, incidence and mortality rates of endometrial cancer (EC) are still increasing. The E2F family of transcriptional factors is involved in cell differentiation, apoptosis, and inhibition of DNA damage response, thus affecting growth and invasion of tumor cells.

Methods: We used multiple bioinformatics tools to explore the role of E2F family in endometrial cancer.

Results: The expression of E2F1/2/3/7/8 was significantly upregulated in endometrial cancer tissues, converse to E2F4, which was downregulated. Methylation downregulates all E2Fs except for E2F2. Accordingly, E2F1/2/3/5/7/8 are potential diagnostic biomarkers for EC. In particular, EC patients displaying upregulated E2F1, and E2F3 expression had a worse overall survival and relapse-free survival. E2F8, E2F7, and E2F1 were the top three, most-frequently altered genes in endometrial cancer. E2F family activates apoptosis pathways, regulates cell cycle, and impairs DNA damage response pathways. Drug-sensitivity analysis demonstrated that the level of E2F2/3/8 negatively correlated with drug resistance. Meanwhile, immune infiltrations analysis revealed that E2F family is associated with recruitment of several immune cells. Enrichment analysis on its part revealed that the E2F family is mainly associated with cell cycle, sequence-specific DNA binding, nuclear transcription factor complex, PI3K-Akt signaling, and p53 signaling pathway. We also identified multiple E2Fs-associated miRNA and kinase targets in endometrial cancer.

Conclusion: Our study revealed the unique expression signature and clinical significance of E2F family in EC, demonstrating the potential clinical utility of these transcription factors (TF) in endometrial cancer.
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http://dx.doi.org/10.3389/fgene.2020.557188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672218PMC
November 2020

Identification and characterization of older emergency department patients with high-risk alcohol use.

J Am Coll Emerg Physicians Open 2020 Oct 17;1(5):804-811. Epub 2020 Jul 17.

Department of Emergency Medicine Yale School of Medicine New Haven Connecticut USA.

Background: High-risk alcohol use in the elderly is a common but underrecognized problem. We tested a brief screening instrument to identify high-risk individuals.

Methods: This was a prospective, cross-sectional study conducted at a single emergency department. High-risk alcohol use was defined by National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines as >7 drinks/week or >3 drinks/occasion. We assessed alcohol use in patients aged ≥ 65 years using the timeline follow back (TLFB) method as a reference standard and a new, 2-question screener based on NIAAA guidelines. The Alcohol Use Disorders Identification Test (AUDIT) and Cut down, Annoyed, Guilty, Eye-opener (CAGE) screens were used for comparison. We collected demographic information from a convenience sample of high- and low-risk drinkers.

Results: We screened 2250 older adults and 180 (8%) met criteria for high-risk use. Ninety-eight high-risk and 124 low-risk individuals were enrolled. The 2-question screener had sensitivity of 98% (95% CI, 93%-100%) and specificity of 87% (95% CI, 80%-92%) using TLFB as the reference. It had higher sensitivity than the AUDIT or CAGE tools. The high-risk group was predominantly male (65% vs 35%, < 0.001). They drank a median of 14 drinks per week across all ages from 65 to 92. They had higher rates of prior substance use treatment (17% vs 2%, < 0.001) and current tobacco use (24% vs 9%, = 0.004).

Conclusion: A rapid, 2-question screener can identify high-risk drinkers with higher sensitivity than AUDIT or CAGE screening. It could be used in concert with more specific questionnaires to guide treatment.
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http://dx.doi.org/10.1002/emp2.12196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593462PMC
October 2020

Variation of net anthropogenic phosphorus inputs (NAPI) and riverine phosphorus fluxes in seven major river basins in China.

Sci Total Environ 2020 Nov 29;742:140514. Epub 2020 Jun 29.

College of Environmental Science and Engineering, Beijing Forestry University, Beijing 100083, China. Electronic address:

The riverine phosphorus (P) import resulting from human activities is always a worldwide concern for environmental management due to the effect of eutrophication. In this study, we made modification of the NAPI method to make the results closer to the actual situation. We collected the data of seven major outflow rivers in China to have a comprehensive understanding of P export and P inputs and build the quantitative relationship between them. We estimated the net anthropogenic phosphorus inputs (NAPI), including fertilizer P (P), net food and feed import P and non-food P using by human (P), in seven major river basins in China and the corresponding riverine total phosphorus (TP) fluxes. The relationship between NAPI and riverine TP flux was also explored. NAPI in seven river basins presented an obvious uneven distribution. Huaihe River basin showed the highest NAPI of 4005.09 kg P km yr due to its highest intensities of human-activities, and the lowest NAPI was observed in Songhua River basin as 334.36 kg P km yr. P occupied a larger proportion of NAPI in the Pearl River and Liaohe River basins (> 65%), while P contributed more to NAPI in the other basins (nearly 60%) with an exception of the Yangtze River basin (where P and P approximately contributed the same). Different contributions of NAPI components were mainly attributed to the different land uses. The total TP flux of all the seven rivers was 117.10 × 10 t P yr, with the highest flux in the Yangtze River (77.42 × 10 t P yr), contributed 72.88% to the total TP fluxes in China. Change in riverine TP flux could be well described by NAPI, river discharge, and percentage of lake area in the basin and this provided an effective way to predict TP fluxes in rivers.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140514DOI Listing
November 2020

27-Hydroxycholesterol contributes to cognitive deficits in APP/PS1 transgenic mice through microbiota dysbiosis and intestinal barrier dysfunction.

J Neuroinflammation 2020 Jun 27;17(1):199. Epub 2020 Jun 27.

School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, 100069, China.

Background: Research on the brain-gut-microbiota axis has led to accumulating interest in gut microbiota dysbiosis and intestinal barrier dysfunction in Alzheimer's disease (AD). Our previous studies have demonstrated neurotoxic effects of 27-hydroxycholesterol (27-OHC) in in vitro and in vivo models. Here, alterations in the gut microbiota and intestinal barrier functions were investigated as the possible causes of cognitive deficits induced by 27-OHC treatment.

Methods: Male APP/PS1 transgenic and C57BL/6J mice were treated for 3 weeks with 27-OHC (5.5 mg/kg/day, subcutaneous injection) and either a 27-OHC synthetase inhibitor (anastrozole, ANS) or saline. The Morris water maze and passive avoidance test were used to assess cognitive impairment. Injuries of the intestine were evaluated by histopathological examination. Intestinal barrier function was assessed by plasma diamine oxidase (DAO) activity and D-lactate. Systemic and intestinal inflammation were evaluated by IL-1β, TNF-α, IL-10, and IL-17 concentrations as determined by ELISA. The fecal microbiome and short-chain fatty acids (SCFAs) were analyzed using 16S rDNA sequencing and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Tight junction proteins were evaluated in the ileum and colon by qRT-PCR and Western blots. Tight junction ultrastructure was examined by transmission electron microscopy.

Results: Treatment with 27-OHC resulted in severe pathologies in the ileum and colon. There was impaired intestinal barrier integrity as indicated by dilated tight junctions and downregulation of tight junction proteins, including occludin, claudin 1, claudin 5, and ZO-1, and signs of inflammation (increased IL-1β, TNF-α, and IL-17). Fecal 16S rDNA sequencing and taxonomic analysis further revealed a decreased abundance of Roseburia and reduced fecal levels of several SCFAs in 27-OHC-treated mice. Meanwhile, co-treatment with ANS reduced intestinal inflammation and partially preserved intestinal barrier integrity in the presence of 27-OHC.

Conclusions: The current study demonstrates for the first time that 27-OHC treatment aggravates AD-associated pathophysiological alterations, specifically gut microbiota dysbiosis and intestinal barrier dysfunction, which suggests that the gut microbiome and intestinal barrier function warrant further investigation as potential targets to mitigate the neurotoxic impact of 27-OHC on cognitive function and the development of AD.
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http://dx.doi.org/10.1186/s12974-020-01873-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321549PMC
June 2020

The effect of colonic tissue electrical stimulation and celiac branch of the abdominal vagus nerve neuromodulation on colonic motility in anesthetized pigs.

Neurogastroenterol Motil 2020 11 23;32(11):e13925. Epub 2020 Jun 23.

Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, CURE: Digestive Diseases Research Center (DDRCC), Center for Neurobiology of Stress and Resilience (CNSR), University of California Los Angeles, Los Angeles, CA, USA.

Background: Knowledge on optimal electrical stimulation (ES) modalities and region-specific functional effects of colonic neuromodulation is lacking. We aimed to map the regional colonic motility in response to ES of (a) the colonic tissue and (b) celiac branch of the abdominal vagus nerve (CBVN) in an anesthetized porcine model.

Methods: In male Yucatan pigs, direct ES (10 Hz, 2 ms, 15 mA) of proximal (pC), transverse (tC), or distal (dC) colon was done using planar flexible multi-electrode array panels and CBVN ES (2 Hz, 0.3-4 ms, 5 mA) using pulse train (PT), continuous (10 min), or square-wave (SW) modalities, with or without afferent nerve block (200 Hz, 0.1 ms, 2 mA). The regional luminal manometric changes were quantified as area under the curve of contractions (AUC) and luminal pressure maps generated. Contractions frequency power spectral analysis was performed. Contraction propagation was assessed using video animation of motility changes.

Key Results: Direct colon ES caused visible local circular (pC, tC) or longitudinal (dC) muscle contractions and increased luminal pressure AUC in pC, tC, and dC (143.0 ± 40.7%, 135.8 ± 59.7%, and 142.0 ± 62%, respectively). The colon displayed prominent phasic pressure frequencies ranging from 1 to 12 cpm. Direct pC and tC ES increased the dominant contraction frequency band (1-6 cpm) power locally. Pulse train CBVN ES (2 Hz, 4 ms, 5 mA) triggered pancolonic contractions, reduced by concurrent afferent block. Colon contractions propagated both orally and aborally in short distances.

Conclusion And Inferences: In anesthetized pigs, the dominant contraction frequency band is 1-6 cpm. Direct colonic ES causes primarily local contractions. The CBVN ES-induced pancolonic contractions involve central neural network.
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http://dx.doi.org/10.1111/nmo.13925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606494PMC
November 2020

Association between nutrition support and acute gastrointestinal injury in critically ill patients during the first 72 hours.

Clin Nutr 2021 01 18;40(1):217-221. Epub 2020 May 18.

Intensive Care Unit, First Hospital of Jilin University, Changchun, China. Electronic address:

Background & Aims: The impact of nutrition support on patients with acute gastrointestinal injury (AGI) has not been fully determined. This study aimed to 1) investigate the relationship between nutrition support and AGI, as well as nutrition support and prognosis in critically ill AGI patients and 2) evaluate the prognostic benefits of nutrition support in different severity categories of AGI patients.

Methods: This prospective study included 379 patients in whom AGI occurred in the first 72 h after admission from 12 teaching hospitals in China. Clinical characteristics including demographics, APACHE II score, modified NUTRIC score, SOFA score, calories of nutrition, and 7 and 28-day mortality were recorded. Multiple logistic regression analysis was applied to identify the risk factors for mortality. The survival benefit of nutrition support as reflected by calories of nutrition in 72 h was evaluated for patients categorized according to their APACHE II, modified NUTRIC, and SOFA scores.

Results: Patients were classified into Grades I (n = 141), II (n = 173), III (n = 48), and IV (n = 17). Significant differences were observed among different AGI grade cohorts (I-IV) in terms of APACHE II, SOFA, and modified NUTRIC scores and calories of enteral nutrition (EN), parenteral nutrition (PN), and EN + PN. Ordinal logistic regression analysis showed that only SOFA score was an independent risk factor for AGI grades (P < 0.001). APACHE II score, mechanical ventilation (MV), AGI grades, and calories of EN + PN intake were independent risk factors for 28-d mortality. Increased nutritional intake was associated with reduced mortality in severely ill patients with APACHE II scores ≥15 (P = 0.007).

Conclusions: AGI grade affected the intake of calories and was one of the risk factors for 28-d mortality. The nutrition intake of patients with AGI grade III to IV was almost only PN. The positive association between nutrition support and prognosis was more apparent in AGI patients with higher APACHE II scores.
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http://dx.doi.org/10.1016/j.clnu.2020.05.011DOI Listing
January 2021

[Stratified outcomes of "Kidney Disease: Improving Global Outcomes" serum creatinine criteria in critical ill patients: a secondary analysis of a multicenter prospective study].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Mar;32(3):313-318

Medical Intensive Care Unit, Peking Union Medical College Hospital, Beijing 100730, China.

Objective: To investigate the different outcomes of two types of acute kidney injury (AKI) according to standard of Kidney Disease: Improving Global Outcomes-AKI (KDIGO-AKI), and to analyze the risk factors that affect the prognosis of intensive care unit (ICU) patients in China.

Methods: A secondary analysis was performed on the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a multicenter prospective study involving 3 063 patients in 22 tertiary ICUs in 19 provinces and autonomous regions of China. The demographic data, scores reflecting severity of illness, laboratory findings, intervention during ICU stay were extracted. All patients were divided into pure AKI (PAKI) and acute on chronic kidney disease (AoCKD). PAKI was defined as meeting the serum creatinine (SCr) standard of KDIGO-AKI (KDIGO-AKI) and the estimated glomerular filtration rate (eGFR) at baseline was ≥ 60 mL×min×1.73 m, and AoCKD was defined as meeting the KDIGO-AKI standard and baseline eGFR was 15-59 mL×min×1.73 m. All-cause mortality in ICU within 28 days was the primary outcome, while the length of ICU stay and renal replacement therapy (RRT) were the secondary outcome. The differences in baseline data and outcomes between the two groups were compared. The cumulative survival rate of ICU within 28 days was analyzed by Kaplan-Meier survival curve, and the risk factors of ICU death within 28 days were screened by Cox multivariate analysis.

Results: Of the 3 063 patients, 1 042 were enrolled, 345 with AKI, 697 without AKI. The AKI incidence was 33.11%, while ICU mortality within 28 days of AKI patients was 13.91% (48/345). Compared with PAKI patients (n = 322), AoCKD patients (n = 23) were older [years old: 74 (59, 77) vs. 58 (41, 72)] and more critical when entering ICU [acute physiology and chronic health evaluation II (APACHE II) score: 23 (19, 27) vs. 15 (11, 22)], had worse basic renal function [eGFR (mL×min×1.73 m): 49 (38, 54) vs. 115 (94, 136)], more basic complications [Charlson comorbidity index (CCI): 3 (2, 4) vs. 0 (0, 1)] and higher SCr during ICU stay [peak SCr for diagnosis of AKI (μmol/L): 412 (280, 515) vs. 176 (124, 340), all P < 0.01]. The mortality and RRT incidence within 28 days in ICU of AoCKD patients were significantly higher than those of PAKI patients [39.13% (9/23) vs. 12.11% (39/322), 26.09% (6/23) vs. 4.04% (13/322), both P < 0.01], while no significant difference was found in the length of ICU stay. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate in ICU in AoCKD patients was significantly lower than PAKI patients (Log-Rank: χ = 5.939, P = 0.015). Multivariate Cox regression analysis showed that admission to ICU due to respiratory failure [hazard ratio (HR) = 4.458, 95% confidence interval (95%CI) was 1.141-17.413, P = 0.032], vasoactive agents treatment in ICU (HR = 5.181, 95%CI was 2.033-13.199, P = 0.001), and AoCKD (HR = 5.377, 95%CI was 1.303-22.186, P = 0.020) were independent risk factors for ICU death within 28 days.

Conclusions: Further detailed classification (PAKI, AoCKD) based on KDIGO-AKI standard combined with eGFR is related to ICU mortality in critical patients within 28 days.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200218-00192DOI Listing
March 2020

Macrophage-mimic shape changeable nanomedicine retained in tumor for multimodal therapy of breast cancer.

J Control Release 2020 05 28;321:589-601. Epub 2020 Feb 28.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address:

The current nanomedicines for cancer therapy based on the enhance permeability and retention (EPR) effect remain insufficient to satisfy the clinical need, and the challenges hindering nanomedicines delivery should be conquered for strong therapeutic efficacy. To address these problems, a membrane-coated laser-responsive shape changeable nanomedicine, [email protected]@M, is reported. The covering macrophage membrane promotes the circulation and tumor targeting of nanomedicines. Then the chlorin e6 (Ce6) in [email protected]@M can convert 650 nm laser into reactive oxygen species (ROS) to trigger the spherical micelles changing into nanofibers for strong retention in tumor region, consequently the linear nanofibers long locate and sustainably release drugs. On the other hand, the ROS not only directly kills tumor cells by photodynamic therapy but stimulates the dimeric paclitaxel (PTX) generating monomeric PTX. The combinational chemo- photodynamic therapy heavily suppresses tumor growth and inducing immunogenic cell death, which is synergistic with Indoximod (IND) inhibiting the IDO pathway to activate immune response for immunotherapy. By chemotherapy, photodynamic therapy and immunotherapy gathering, the treatment of [email protected]@M + laser shows the best antitumor effect, resulting in 85.27 ± 12.80% suppression of breast cancer in mice model, and also remarkably inhibits lung metastasis.
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http://dx.doi.org/10.1016/j.jconrel.2020.02.043DOI Listing
May 2020

Longitudinal and nonlinear relations of dietary and Serum cholesterol in midlife with cognitive decline: results from EMCOA study.

Mol Neurodegener 2019 12 30;14(1):51. Epub 2019 Dec 30.

School of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, 100069, China.

Background: Previous studies regarding the cholesterol-cognition relationship in midlife have generated conflicting results. We thus investigated whether dietary and blood cholesterol were associated with cognitive decline.

Methods: Participants were drawn from a large cohort study entitled the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer's disease (EMCOA) study. We included 2514 participants who completed a selection of comprehensive cognitive tests and were followed for an average of 2.3 years. Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were assessed and dietary intakes were investigated by food frequency questionnaire (FFQ) at baseline. Apolipoprotein E (APOE) was genotyped by Kompetitive Allele Specific PCR (KASP) sequencing. Non-high-density lipoprotein cholesterol (Non-HDL-C) and LDL-C/HDL-C ratio were calculated. The longitudinal effects of dietary and blood cholesterol on risk of global cognitive decline (decrease in Montreal Cognitive Assessment (MoCA) > 2 points) were examined using Cox proportional hazards models. The nonlinear associations with global and domain-specific cognitive decline was evaluated with mixed effect linear models.

Results: In Cox proportional hazards models, neither cholesterol nor egg intake was associated with a higher risk of accelerated global cognitive decline. In contrast, the higher serum concentrations of TC, LDL-C, non-HDL-C and LDL-C/HDL-C ratio were positively associated with accelerated global cognitive decline regardless of being evaluated continuously or categorically while higher HDL-C was positively associated with accelerated global cognitive decline only when being evaluated categorically (all P < 0.05). In mixed effect linear models, quadratic and longitudinal relations of dietary cholesterol and egg intakes to global cognition, processing speed and executive function were observed. Moreover, there were inverted U-shaped relations of HDL-C, with processing speed and executive function but U-shaped relations of HDL-C and LDL-C/HDL-C ratio with verbal memory. Adverse linear associations of higher LDL-C and LDL-C/HDL-C ratio with multiple cognitive comes were also revealed. Additionally adjusting for APOE genotype did not modify cholesterol-cognition associations. Dietary and serum cholesterol had variable associations with global and domain-specific cognitive decline across educational groups.

Conclusion: Differential associations between dietary/serum cholesterol and cognitive decline across different domains of function were observed in a particular population of middle-aged and elderly Chinese. Interventions to improve cognitive reserve regarding dietary instruction and lipid management should be tailored according to specific target.

Trial Registration: EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610.
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http://dx.doi.org/10.1186/s13024-019-0353-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937942PMC
December 2019

Dietary intakes and biomarker patterns of folate, vitamin B, and vitamin B can be associated with cognitive impairment by hypermethylation of redox-related genes NUDT15 and TXNRD1.

Clin Epigenetics 2019 10 11;11(1):139. Epub 2019 Oct 11.

School of Public Health, Capital Medical University, No.10 Xitoutiao, You An Men Wai, Beijing, 100069, China.

Background: B vitamins in the one-carbon metabolism pathway (folate, vitamin B, and vitamin B) have been implicated in DNA methylation, and their deficiency may contribute to cognitive decline through increased homocysteine (Hcy) levels and subsequent oxidative damage. The aim of this study was to investigate whether B vitamin deficiency and increased Hcy could interact with DNA methylation of oxidative-related genes and exacerbate cognitive impairment.

Methods: Participants were selected from a large cohort study entitled the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer's disease (EMCOA) study. We included 2533 participants who completed a selection of comprehensive cognitive tests and a semiquantitative food frequency questionnaire (FFQ) and were followed for an average of 2.3 years. The longitudinal effects of B vitamin intake on cognitive decline were examined using linear mixed-effect models. Seven mild cognitive impairment (MCI) patients, in the predementia stage of Alzheimer's disease (AD), and fivev healthy controls were selected for the discovery of genome-wide differentially methylated CpG sites. Candidate oxidative stress-related genes significantly correlated with serum levels of B vitamins were selected for validation in 102 MCI patients and 68 controls. The correlations between DNA methylation levels and serum concentrations of B vitamins and oxidative biomarkers were analyzed with Spearman's correlation. The interactive effects of DNA methylation and B vitamins on cognitive performance were further evaluated by multiple linear regression.

Results: In the prospective analysis, inadequate dietary intake of vitamin B was significantly associated with accelerated cognitive decline, whereas adequate folate, vitamin B, and vitamin B intakes were significantly associated with better cognitive reserve. In the case-control analysis, the DNA methylation levels of NUDT15 and TXNRD1 were examined, and significantly hypermethylated sites were identified in MCI patients. Significant correlations of hypermethylated sites with serum levels of folate, homocysteine (Hcy), and oxidative biomarkers were observed, and interactive effects of B vitamins and hypermethylated sites were significantly associated with cognitive performance.

Conclusion: Adequate dietary folate at baseline predicted a better cognitive reserve, while decreased serum levels of B vitamins may contribute to cognitive impairment by affecting methylation levels of specific redox-related genes.

Trial Registration: EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610.
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http://dx.doi.org/10.1186/s13148-019-0741-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787977PMC
October 2019

Dietary Intake of Riboflavin and Unsaturated Fatty Acid Can Improve the Multi-Domain Cognitive Function in Middle-Aged and Elderly Populations: A 2-Year Prospective Cohort Study.

Front Aging Neurosci 2019 29;11:226. Epub 2019 Aug 29.

School of Public Health, Capital Medical University, Beijing, China.

Objective: This study was aimed to explore the effects of dietary nutrients on cognitive function among the middle-aged and elderly populations.

Methods: A prospective cohort study of 1,385 middle-aged and elderly people was conducted from January 2014 to December 2017. Dietary nutrients were assessed according to the food frequency questionnaire (FFQ) and China Food Composition Database (CFCD). Montreal cognitive assessment (MoCA) was used to evaluate the participants' global cognitive function. Six other neuropsychological measures [auditory verbal learning test-immediate recall (AVLT-IR), auditory verbal learning test-short recall (AVLT-SR), auditory verbal learning test-long recall (AVLT-LR), logical memory test (LMT), digit span forward (DST-F), and digit span backward (DST-B)] were used to assess the verbal memory domain and the attention domain by principal component analysis (PCA). Multiple linear regressions were conducted to explore associations between nutrients and cognition. Sensitivity analyses were performed to confirm the results.

Results: Dietary riboflavin was protective for global cognitive function (β = 1.31, 95% CI: 0.26, 2.35) and the verbal memory domain (β = 0.37, 95% CI: 0.02, 0.71). Unsaturated fatty acid (USFA) played a protective role in global cognitive function (β = 1.15, 95% CI: 0.16, 2.14). The protective effects of riboflavin and USFA on cognitive function were consistent and reliable when different confounders were adjusted during sensitivity analyses. During the follow-up, neuropsychological measure scores revealed a reduced decline in the high-riboflavin group (d-MoCA, = 0.025; d-AVLT-IR, = 0.001; d-DST-B, = 0.004; and d-composite score, = 0.004) and the high-USFA group (d-AVLT-IR, = 0.007; d-LMT, = 0.032; d-DST-B, = 0.002; and d-composite score, = 0.008).

Conclusion: Higher intake of riboflavin and USFA can improve multi-dimensional cognitive functioning in middle-aged and elderly people. These findings were consistent in different models of sensitivity analyses.
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http://dx.doi.org/10.3389/fnagi.2019.00226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727035PMC
August 2019

Fermented ginseng improved alcohol liver injury in association with changes in the gut microbiota of mice.

Food Funct 2019 Sep 20;10(9):5566-5573. Epub 2019 Aug 20.

College of Food Science and Engineering, China and Jilin province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China and National Processing Laboratory for Soybean Industry and technology, Changchun, China.

The interactions among the liver, intestine and immune system play an important role in alcoholic liver injury. In this study, C57BL/6N mice with alcoholic injury were treated with unfermented and Lactobacillus fermentum KP-3-fermented ginseng. The indicators of hepatic steatosis, inflammation and injury were evaluated. The number of beneficial and harmful bacteria in the mice ileum and colon was counted by a traditional method; moreover, the diversity analysis of the cecum flora was performed. The alcohol exposure increased the levels of ALT, AST, TNF-α and IL-6 inflammatory factors and liver steatosis. In addition, the alcohol-fed miceexhibited a lower number of Lactobacilli and Bifidobacteria in the ileum and colon; the cecum flora diversity in the mice showed that alcohol obviously enhanced the abundance of the unclassified S24-7 of the Bacteroidetes phylum and the Proteobacteria genus of the Sutterella phylum and reduced the abundance of short-chain fatty acid-producing bacteria such as Akkermansia in the Verrucomicrobia phylum and those belonging to the Allobaculum genus, the Ruminococcus genus, and the Adlercreutzia genus in the Actinobacteria phylum. All these changes were improved by fermented ginseng. Conclusively, fermented ginseng could alleviate the alcoholic liver injury and disorder of the intestine by adjusting the intestinal flora.
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http://dx.doi.org/10.1039/c9fo01415bDOI Listing
September 2019

27-Hydroxycholesterol Contributes to Lysosomal Membrane Permeabilization-Mediated Pyroptosis in Co-cultured SH-SY5Y Cells and C6 Cells.

Front Mol Neurosci 2019 1;12:14. Epub 2019 Mar 1.

Beijing Key Laboratory of Environmental Toxicology, School of Public Health, Capital Medical University, Beijing, China.

: Emerging evidence suggests that 27-Hydroxycholesterol (27-OHC) causes neurodegenerative diseases through the induction of cytotoxicity and cholesterol metabolism disorder. The objective of this study is to determine the impacts of 27-OHC on lysosomal membrane permeabilization (LMP) and pyroptosis in neurons in the development of neural degenerative diseases. : In this study, SH-SY5Y cells and C6 cells were co-cultured to investigate the influence of 27-OHC on the function of lysosome, LMP and pyroptosis related factors in neuron. Lyso Tracker Red (LTR) was used to detect the changes of lysosome pH, volume and number. Acridine orange (AO) staining was also used to detect the LMP in neurons. Then the morphological changes of cells were observed by a scanning electron microscope (SEM). The content of lysosome function associated proteins [including Cathepsin B (CTSB), Cathepsin D (CTSD), lysosomal-associated membraneprotein-1 (LAMP-1), LAMP-2] and the pyroptosis associated proteins [including nod-like recepto P3 (NLRP3), gasdermin D (GSDMD), caspase-1 and interleukin (IL)-1β] were detected through Western blot. : Results showed higher levels of lysosome function associated proteins, such as CTSB ( < 0.05), CTSD ( < 0.05), LAMP-1 ( < 0.01), LAMP-2; < 0.01) in 27-OHC treated group than that in the control group. AO staining and LTR staining showed that 27-OHC induced lysosome dysfunction with LMP. Content of pyroptosis related factor proteins, such as GSDMD ( < 0.01), NLRP3 ( < 0.001), caspase-1 ( < 0.01) and IL-1β ( < 0.01) were increased in 27-OHC treated neurons. Additionally, CTSB was leaked through LMP into the cytosol and induced pyroptosis. Results from the present study also suggested that the CTSB is involved in activation of pyroptosis. : Our data indicate that 27-OHC contributes to the pathogenesis of cell death by inducing LMP and pyroptosis in neurons.
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http://dx.doi.org/10.3389/fnmol.2019.00014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405519PMC
March 2019

27-Hydroxycholesterol Alters Synaptic Structural and Functional Plasticity in Hippocampal Neuronal Cultures.

J Neuropathol Exp Neurol 2019 03;78(3):238-247

School of Public Health, Capital Medical University, Beijing, China.

This study aimed to explore the neurotoxic effects of 27-hydroxycholesterol (27-OHC), a major circulating cholesterol active derivative in brain on synaptic structural and functional plasticity in primary hippocampal neurons. Newborn SD rat primary hippocampal neurons were treated with 0, 1, 3, 10, and 30 μM 27-OHC for 24 hours. MTT and CCK-8 assays were used to monitor the cell viability of neurons with different treatments. Neurite morphology was assessed by staining for microtubule-associated protein-2 (MAP2) and analyzed by immunofluorescence. Synaptic ultrastructure was evaluated by transmission electron microscopy. Real-time polymerase chain reaction and Western blot analyses were used to evaluate the expression of key synaptic proteins: synaptophysin (SYP), postsynaptic density protein-95 (PSD-95), synaptosomal-associated protein 25 (SNAP-25), growth-associated protein-43 (GAP-43), MAP2, and activity-regulated cytoskeleton-associated protein (Arc). Treatment with 27-OHC at various doses stimulated cell death and resulted in significant decreases in neurite number and length, alteration of synaptic ultrastructure, and downregulated expression of synaptic proteins in a dose-dependent manner. These results suggest that 27-OHC is deleterious for synaptic structural and functional plasticity, which may partially account for its neurotoxic effects.
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http://dx.doi.org/10.1093/jnen/nlz002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967841PMC
March 2019

27-hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice.

Brain Pathol 2019 07 22;29(4):558-573. Epub 2019 Jan 22.

School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.

The oxysterol 27-hydroxycholesterol (27-OHC) has been considered to play a key role in the pathogenesis of Alzheimer's disease (AD). Because β-amyloid peptide (Aβ) is the pathological hallmark of AD, the aim of this study is to verify whether 27-OHC could lead to cognitive impairment through modulating Aβ accumulation and deposition. Regulation of Aβ metabolism was explored as the pathogenic mechanism of 27-OHC. Furthermore, microRNAs (miRNAs) and their relations with 27-OHC were also detected. In present study, matched case-control study and APP/PS1 transgenic mice research were conducted. The results showed that the 27-OHC and Aβ in plasma were increased in mild cognitive impairment patients, and a slight correlation was found between 27-OHC and Aβ1-40. This relationship was also proved by the research of APP/PS1 mice. More severe learning and memory impairment and higher Aβ1-40 expression in brain and plasma were detected in the APP/PS1 mice of 27-OHC treatment group. In addition, increased amyloid plaques were also found in the hippocampus of 27-OHC-treated mice. In order to find out the mechanism of 27-OHC on regulating Aβ metabolism, the factors of Aβ production (APP, BACE1 and ADAM10), transport (LRP1 and RAGE) and elimination (NEP and IDE) were tested respectively. The gene and protein expressions of APP, BACE1 and RAGE were increased while LRP1 and IDE were decreased in the brain of 27-OHC-treated mice. At last, down-regulated expression of miRNA let-7g-5p was found after 27-OHC treatment. In conclusion, these findings suggested that excessive 27-OHC could enhance the accumulation and deposition of Aβ both in brain and blood, resulting in a severe impairment of cognition, especially in the modulation of Aβ1-40. The mechanism might be associated with the regulation of Aβ metabolism, and miRNA let-7g-5p was likely to play a vital role in this pathological process induced by 27-OHC.
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http://dx.doi.org/10.1111/bpa.12698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028629PMC
July 2019

Nitroxide-radicals-modified gold nanorods for in vivo CT/MRI-guided photothermal cancer therapy.

Int J Nanomedicine 2018 6;13:7123-7134. Epub 2018 Nov 6.

College of Engineering and Applied Science, Nanjing University, Nanjing, Jiangsu, 210093, People's Republic of China,

Purpose: This article presents a report of the synthesis, characterization, and biomedical application of nitroxide-radicals-modified gold nanorods (Au-TEMPO NRs) for imaging-guided photothermal cancer therapy.

Patients And Methods: Au nanorods were synthesized through seed-mediated growth method, 4-Amino-TEMPO was added and the reaction proceeded under magnetic stirring.

Results: With a mean length of 39.2 nm and an average aspect ratio of approximately 3.85, Au-TEMPO NRs showed good photothermal ability when they were irradiated by 808-nm laser. Au-TEMPO NRs could be stored in PBS for more than 1 month, showed no cytotoxicity against both tumor and normal cells at a concentration of up to 3 mg/mL, and functioned as a dual-mode contrast agent for CT/magnetic resonance (MR) imaging in vitro and in vivo, due to their high X-ray attenuation of Au and good r1 relaxivity of nitroxide radicals. Further, they had a long retention time (~4 hours) in the main organs, which enabled a long CT/MR imaging time window for diagnosis. Bio-distribution results revealed that these Au-TEMPO NRs passively aggregated in the liver and spleen. After irradiation by 808-nm laser, Au-TEMPO NRs could ablate the solid tumor in 4T1 tumor-bearing mice, which implied they were a potential theranostic agent for dual-mode imaging and photothermal cancer therapy.

Conclusion: This type of Au-TEMPO NRs with the abilities of CT/MR imaging and photothermal therapy, can play an active role in imaging-guided photothermal cancer therapy.
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http://dx.doi.org/10.2147/IJN.S171804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6228083PMC
December 2018

Improving EEG Source Localization with a Novel Regularization: Spatiotemporal Graph Total Variation (STGTV) Method.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:4673-4676

Electroencephalography (EEG) source Iocalization aims at reconstructing the current density on the brain cortex from scalp EEG recordings. It of ten starts with a generative model that maps brain activity to the EEG recording, and then solves the inverse problem. Previously proposed method graph fractional-order total variation (gFOTV) is based on spatial regularization, and was shown superior to some other existing spatial-regularized methods in simulation tests. However, the gFOTV addresses inverse problem for one time point at a time. The resultant estimated times series of brain activity is a simple concatenation of reconstructions independently performed at each time instance, and risks spurious temporal discontinuity due to overfitting noise in EEG recordings. In addition, the performance is subject to low signal-to-noise ratio (SNR) and small number of electrodes, which happens in realistic EEG recordings. To account for the generally continuous temporal variation in brain activity, but also allow for properly triggering abrupt changes, we propose a novel formulation that incorporates spatiotemporal regularization. Specifically, our method, called spatiotemporal graph total variation (STGTV) adopts graph fractional-order total variation (gFOTV) for spatial regularization and total variation (TV) for temporal regularization. The gFOTV encourages spatially smooth source distributions, and the temporal TV enhances temporal consistency in estimated activity maps. The introduction of implicit temporal coupling by temporal TV also helps with noise cancelation and enhances SNR. In a simulation study, the performance of the proposed method was compared against that from the gFOTV regularization alone. The results showed that the proposed STGTV method significantly improved gFOTV, with lower Iocalization errors and less spuriously discovered sources.
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http://dx.doi.org/10.1109/EMBC.2018.8513128DOI Listing
July 2018
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