Publications by authors named "Long Xie"

93 Publications

Oh brother, where art tau? Amyloid, neurodegeneration, and cognitive decline without elevated tau.

Neuroimage Clin 2021 Jun 6;31:102717. Epub 2021 Jun 6.

Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.

Mild cognitive impairment (MCI) can be an early manifestation of Alzheimer's disease (AD) pathology, other pathologic entities [e.g., cerebrovascular disease, Lewy body disease, LATE (limbic-predominant age-related TDP-43 encephalopathy)], or mixed pathologies, with concomitant AD- and non-AD pathology being particularly common, albeit difficult to identify, in living MCI patients. The National Institute on Aging and Alzheimer's Association (NIA-AA) A/T/(N) [β-Amyloid/Tau/(Neurodegeneration)] AD research framework, which classifies research participants according to three binary biomarkers [β-amyloid (A+/A-), tau (T+/T-), and neurodegeneration (N+/N-)], provides an indirect means of identifying such cases. Individuals with A+T-(N+) MCI are thought to have both AD pathologic change, given the presence of β-amyloid, and non-AD pathophysiology, given neurodegeneration without tau, because in typical AD it is tau accumulation that is most tightly linked to neuronal injury and cognitive decline. Thus, in A+T-(N+) MCI (hereafter referred to as "mismatch MCI" for the tau-neurodegeneration mismatch), non-AD pathology is hypothesized to drive neurodegeneration and symptoms, because β-amyloid, in the absence of tau, likely reflects a preclinical stage of AD. We compared a group of individuals with mismatch MCI to groups with A+T+(N+) MCI (or "prodromal AD") and A-T-(N+) MCI (or "neurodegeneration-only MCI") on cross-sectional and longitudinal cognition and neuroimaging characteristics. β-amyloid and tau status were determined by CSF assays, while neurodegeneration status was based on hippocampal volume on MRI. Overall, mismatch MCI was less "AD-like" than prodromal AD and generally, with some exceptions, more closely resembled the neurodegeneration-only group. At baseline, mismatch MCI had less episodic memory loss compared to prodromal AD. Longitudinally, mismatch MCI declined more slowly than prodromal AD across all included cognitive domains, while mismatch MCI and neurodegeneration-only MCI declined at comparable rates. Prodromal AD had smaller baseline posterior hippocampal volume than mismatch MCI, and whole brain analyses demonstrated cortical thinning that was widespread in prodromal AD but largely restricted to the medial temporal lobes (MTLs) for the mismatch and neurodegeneration-only MCI groups. Longitudinally, mismatch MCI had slower rates of volume loss than prodromal AD throughout the MTLs. Differences in cross-sectional and longitudinal cognitive and neuroimaging measures between mismatch MCI and prodromal AD may reflect disparate underlying pathologic processes, with the mismatch group potentially being driven by non-AD pathologies on a background of largely preclinical AD. These findings suggest that β-amyloid status alone in MCI may not reveal the underlying driver of symptoms with important implications for enrollment in clinical trials and prognosis.
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http://dx.doi.org/10.1016/j.nicl.2021.102717DOI Listing
June 2021

Apoptosis in platelets from adult patients with chronic idiopathic thrombocytopenic purpura.

Blood Coagul Fibrinolysis 2021 Jun 7. Epub 2021 Jun 7.

Department of Clinical Laboratory Medicine Division of Urological Surgery Division of Hematology Division of Respirology Department of Blood Purification Department of Pathology Division of Inventional Ultrasonic Therapeutics, the Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China.

Adult chronic idiopathic thrombocytopenic purpura (cITP) is a chronic and usually life-long haemorrhagic disorder in which enhanced platelet destruction and weakened platelet production lead to thrombocytopenia. Platelets were isolated from blood samples collected from 40 adult patients with cITP and 40 healthy volunteers. Mitochondrial membrane potential (ΔΨm) and plasma membrane phosphatidylserine externalization were determined by flow cytometry, and activation of caspase-3 and expressions of Bax, Bak and Bcl-xL were analysed by western blotting. Flow cytometry showed increased mitochondrial depolarization and lower ΔΨm in platelets from adult patients with cITP. In addition, plasma membrane phosphatidylserine externalization was observed on platelets from adult patients with cITP, but rarely from healthy volunteers. Western blot analysis of platelet proteins revealed that, in adult cITP patients, caspase-3 was activated, which cleaved gelsolin and to release a 47-kDa fragment. Moreover, the expressions of Bax and Bak were elevated, and Bcl-xL was decreased markedly in platelets from adult patients with cITP. Our findings reveal, based on loss of mitochondrial membrane potential (Δψm), phosphatidylserine exposure, caspase-3 activation, enhanced expression of Bax and Bak, and attenuated expression of Bcl-xL, that platelet death in the pathogenesis of thrombocytopenia in chronic ITP in adults is apoptotic.
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http://dx.doi.org/10.1097/MBC.0000000000001054DOI Listing
June 2021

Subspecialty-Level Deep Gray Matter Differential Diagnoses with Deep Learning and Bayesian Networks on Clinical Brain MRI: A Pilot Study.

Radiol Artif Intell 2020 Sep 23;2(5):e190146. Epub 2020 Sep 23.

Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104 (J.D.R., L.X., A.K., J.M.E., T.C., I.M.N., S.M., J.C.G.); Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, Calif (J.D.R., A.M.R.); Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, Pa (X.L., J.W.); University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa (M.T.D.); Mecklenburg Radiology Associates, Charlotte, NC (E.J.B.); Department of Radiology, University of Texas, Austin, Tex (R.N.B.); and Division of Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pa (I.M.N.).

Purpose: To develop and validate a system that could perform automated diagnosis of common and rare neurologic diseases involving deep gray matter on clinical brain MRI studies.

Materials And Methods: In this retrospective study, multimodal brain MRI scans from 212 patients (mean age, 55 years ± 17 [standard deviation]; 113 women) with 35 neurologic diseases and normal brain MRI scans obtained between January 2008 and January 2018 were included (110 patients in the training set, 102 patients in the test set). MRI scans from 178 patients (mean age, 48 years ± 17; 106 women) were used to supplement training of the neural networks. Three-dimensional convolutional neural networks and atlas-based image processing were used for extraction of 11 imaging features. Expert-derived Bayesian networks incorporating domain knowledge were used for differential diagnosis generation. The performance of the artificial intelligence (AI) system was assessed by comparing diagnostic accuracy with that of radiologists of varying levels of specialization by using the generalized estimating equation with robust variance estimator for the top three differential diagnoses (T3DDx) and the correct top diagnosis (TDx), as well as with receiver operating characteristic analyses.

Results: In the held-out test set, the imaging pipeline detected 11 key features on brain MRI scans with 89% accuracy (sensitivity, 81%; specificity, 95%) relative to academic neuroradiologists. The Bayesian network, integrating imaging features with clinical information, had an accuracy of 85% for T3DDx and 64% for TDx, which was better than that of radiology residents ( = 4; 56% for T3DDx, 36% for TDx; < .001 for both) and general radiologists ( = 2; 53% for T3DDx, 31% for TDx; < .001 for both). The accuracy of the Bayesian network was better than that of neuroradiology fellows ( = 2) for T3DDx (72%; = .003) but not for TDx (59%; = .19) and was not different from that of academic neuroradiologists ( = 2; 84% T3DDx, 65% TDx; > .09 for both).

Conclusion: A hybrid AI system was developed that simultaneously provides a quantitative assessment of disease burden, explainable intermediate imaging features, and a probabilistic differential diagnosis that performed at the level of academic neuroradiologists. This type of approach has the potential to improve clinical decision making for common and rare diseases.© RSNA, 2020.
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http://dx.doi.org/10.1148/ryai.2020190146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082339PMC
September 2020

Proteomic Analysis Identifies Potential Markers for Chicken Primary Follicle Development.

Animals (Basel) 2021 Apr 13;11(4). Epub 2021 Apr 13.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530000, China.

Follicles' development in chicken imparts a major impact on egg production. To enhance the egg-laying efficiency, comprehensive knowledge of different phases of follicular development is a prerequisite. Therefore, we used the tandem mass tag (TMT) based proteomic approach to find the genes involved in the primary follicular development of chicken. The primary follicles were divided into two groups-small primary follicles (81-150 μm) and developed primary follicles (300-500 μm). Differential expression analysis (fold change > 1.2, -value < 0.05) revealed a total of 70 differentially expressed proteins (DEPs), of which 38 were upregulated and 32 were downregulated. Gene ontology (GO) enrichment analysis disclosed that DEPs were intricate with cellular protein localization, the establishment of protein localization, and nucleoside phosphate-binding activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway indicated the involvement of DEPs in different metabolic pathways such as glycolysis, pyruvate metabolism, galactose metabolism, and fructose and mannose metabolism. The current proteomic analysis suggested suitable markers such as , and , which may serve as a potential role for primary follicle development. The present study provides the first insight into the proteome dynamics of primary follicle development and would play a potential role for further studies in chicken to improve egg productivity.
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http://dx.doi.org/10.3390/ani11041108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069082PMC
April 2021

Automatic Segmentation of Bone Selective MR Images for Visualization and Craniometry of the Cranial Vault.

Acad Radiol 2021 Apr 23. Epub 2021 Apr 23.

Department of Radiology, University of Pennsylvania, 1 Founders Building, 3400 Spruce Street, Philadelphia, PA 19104-4283; Laboratory for Structural, Physiologic and Functional Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Rationale And Objectives: Solid-state MRI has been shown to provide a radiation-free alternative imaging strategy to CT. However, manual image segmentation to produce bone-selective MR-based 3D renderings is time and labor intensive, thereby acting as a bottleneck in clinical practice. The objective of this study was to evaluate an automatic multi-atlas segmentation pipeline for use on cranial vault images entirely circumventing prior manual intervention, and to assess concordance of craniometric measurements between pipeline produced MRI and CT-based 3D skull renderings.

Materials And Methods: Dual-RF, dual-echo, 3D UTE pulse sequence MR data were obtained at 3T on 30 healthy subjects along with low-dose CT images between December 2018 to January 2020 for this prospective study. The four-point MRI datasets (two RF pulse widths and two echo times) were combined to produce bone-specific images. CT images were thresholded and manually corrected to segment the cranial vault. CT images were then rigidly registered to MRI using mutual information. The corresponding cranial vault segmentations were then transformed to MRI. The "ground truth" segmentations served as reference for the MR images. Subsequently, an automated multi-atlas pipeline was used to segment the bone-selective images. To compare manually and automatically segmented MR images, the Dice similarity coefficient (DSC) and Hausdorff distance (HD) were computed, and craniometric measurements between CT and automated-pipeline MRI-based segmentations were examined via Lin's concordance coefficient (LCC).

Results: Automated segmentation reduced the need for an expert to obtain segmentation. Average DSC was 90.86 ± 1.94%, and average 95th percentile HD was 1.65 ± 0.44 mm between ground truth and automated segmentations. MR-based measurements differed from CT-based measurements by 0.73-1.2 mm on key craniometric measurements. LCC for distances between CT and MR-based landmarks were vertex-basion: 0.906, left-right frontozygomatic suture: 0.780, and glabella-opisthocranium: 0.956 for the three measurements.

Conclusion: Good agreement between CT and automated MR-based 3D cranial vault renderings has been achieved, thereby eliminating the laborious manual segmentation process. Target applications comprise craniofacial surgery as well as imaging of traumatic injuries and masses involving both bone and soft tissue.
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http://dx.doi.org/10.1016/j.acra.2021.03.010DOI Listing
April 2021

Preliminary Investigation about the Expression of G Protein-Coupled Receptors in Platelets from Patients with Chronic Immune Thrombocytopenic Purpura.

Acta Haematol 2021 Apr 13:1-9. Epub 2021 Apr 13.

Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.

Objective: The objective of this study was to determine the expression of G protein-coupled receptors (GPCRs) in platelets from adult patients with chronic immune thrombocytopenic purpura (ITP).

Methods: Peripheral blood samples were collected from 40 patients with chronic ITP in the Second Affiliated Hospital of Shantou University Medical College, and 40 peripheral blood samples from healthy volunteers were collected; expressions of the adenosine diphosphate receptors (P2Y1 and P2Y12), alpha-2A adrenergic receptor (α2A-AR), and thromboxane A2 receptor (TP) in platelets were detected by flow cytometry. Gα protein, protease-activated receptor 1 (PAR1), and protease-activated receptor 4 (PAR4) were analyzed by Western blot and analyzed statistically.

Results: Flow cytometry measurements of mean fluorescence intensities showed platelets from patients with chronic ITP, compared to healthy individuals, had significantly higher levels of P2Y1 (31.4 ± 2.2 vs. 7.8 ± 0.8), P2Y12 (29.6 ± 2.1 vs. 7.2 ± 1.3), α2A-AR (25.8 ± 2.9 vs. 9.8 ± 0.9), and TP (39.8 ± 3.1 vs. 4.7 ± 0.6) (all p < 0.01). Similarly, integrated optical density analysis of Western blots showed that platelets from patients with chronic ITP had significantly higher levels of Gα (1046.3 ± 159.96 vs. 254.49 ± 39.51), PAR1 (832.98 ± 98.81 vs. 203.92 ± 27.47), and PAR4 (1518.80 ± 272.45 vs. 431.27 ± 41.86) (all p < 0.01).

Conclusion: Expression of GPCRs is increased in platelets from patients with chronic ITP, suggesting that platelets of chronic ITP may participate in the complicated biological process by means of GPCR-mediated signaling pathways.
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http://dx.doi.org/10.1159/000514907DOI Listing
April 2021

Preemptive Oral Etoricoxib on Health-Related Quality of Life after Mandibular Third Molar Surgery: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Biomed Res Int 2021 6;2021:8888151. Epub 2021 Mar 6.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

This study was aimed at evaluating the use of oral etoricoxib for preemptive analgesia on the health-related quality of life (QoL) outcome after the extraction of mandibular third molar. The study population consisted of 60 participants that required extraction of a single partial bony impacted mandibular third molar under local anesthesia and met the inclusion criteria. The participants were randomized into two groups. The etoricoxib group orally received 60 mg etoricoxib 30 min before surgery, whereas the control group was given a placebo. The patients were assessed postoperatively after 1, 2, 3, 4, 5, 6, and 7 days using the United Kingdom oral health-related QoL questionnaire and visual analog scale for maximum postoperative pain. The total dose of ibuprofen rescue intake and total number of days the drug was taken were recorded. Surgical removal of impacted teeth had a negative influence on the patient's QoL across various physical, social, and psychological aspects. The scores for postoperative pain in the etoricoxib group were significantly lower than those in the control group on each postoperative observation day. The number of patients without analgesic rescue medication, the average amount, and total number of days emergency analgesics were taken were significantly lower in the etoricoxib group than in the control group. The etoricoxib group showed better QoL score than the control group. Preemptive oral etoricoxib is an effective therapeutic strategy for improving the QoL after surgical removal of the impacted lower third molar.
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http://dx.doi.org/10.1155/2021/8888151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959973PMC
May 2021

Early stages of tau pathology and its associations with functional connectivity, atrophy and memory.

Brain 2021 Mar 16. Epub 2021 Mar 16.

Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, 223 62 Lund, Sweden.

In Alzheimer's disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau-PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior-medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance. We included 215 β-amyloid negative cognitively unimpaired, 81 β-amyloid positive cognitively unimpaired and 87 β-amyloid positive individuals with mild cognitive impairment, who each underwent [18]F-RO948 tau and [18]F-flutemetamol amyloid PET imaging, structural T1-MRI and memory assessments as part of the Swedish BioFINDER-2 study. First, event-based modelling revealed that the entorhinal cortex and area 35 show the earliest signs of tau accumulation followed by the anterior and posterior hippocampus, area 36 and the parahippocampal cortex. In later stages, tau accumulation became abnormal in neocortical temporal and finally parietal brain regions. Second, in cognitively unimpaired individuals, increased tau load was related to local atrophy in the entorhinal cortex, area 35 and the anterior hippocampus and tau load in several anterior medial temporal lobe subregions was associated with distant atrophy of the posterior hippocampus. Tau load, but not atrophy, in these regions was associated with lower memory performance. Further, tau-related reductions in functional connectivity in critical networks between the medial temporal lobe and regions in the posterior-medial system were associated with this early memory impairment. Finally, in patients with mild cognitive impairment, the association of tau load in the hippocampus with memory performance was partially mediated by posterior hippocampal atrophy. In summary, our findings highlight the progression of tau pathology across medial temporal lobe subregions and its disease-stage specific association with memory performance. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical medial temporal lobe-cortical networks, memory impairment in mild cognitively impaired patients is associated with posterior hippocampal atrophy.
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http://dx.doi.org/10.1093/brain/awab114DOI Listing
March 2021

Salidroside: A review of its recent advances in synthetic pathways and pharmacological properties.

Chem Biol Interact 2021 Apr 20;339:109268. Epub 2021 Feb 20.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:

Salidroside has been identified as one of the most potent compounds isolated from various Rhodiola plants, which have been used for a long time as adaptogens in traditional Chinese medicine. However, due to the severe growing environment of herbal medicine and large-scale excavation, the content of natural salidroside is extremely small. Most of the previous studies focused on herbal medicine, and there were few reviews on the synthesis of its main active ingredient salidroside. This paper presents different synthetic routes of salidroside to resolve the contradiction between supply and demand and lays the foundation for new drug research and development. Furthermore, emerging evidence indicates that salidroside, a promising environmentally-adapted drug with low toxicity and few side effects, possesses a wide spectrum of pharmacological properties, including activities on the cardiovascular system and central nervous system, anti-hypoxia, anti-fatigue and anti-aging activities, anticancer activity, anti-inflammatory activity, antioxidant activity, antivirus and immune stimulation activities, antidiabetic activity, anti-osteoporotic activity, and so on. Although the former researches have summarized the pharmacological effects of salidroside, focusing on the central nervous system, diabetes, and cancer, the overall pharmacological aspects of it have not been analyzed. This review highlights biological characteristics and mechanisms of action from 2009 to now as well as toxicological and pharmacokinetic data of the analyzed compound reported so far, with a view to providing a reference for further development and utilization of salidroside.
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http://dx.doi.org/10.1016/j.cbi.2020.109268DOI Listing
April 2021

Calycosin: a Review of its Pharmacological Effects and Application Prospects.

Expert Rev Anti Infect Ther 2020 Dec 21:1-15. Epub 2020 Dec 21.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.

: Calycosin (CA), a typical phytoestrogen extracted from root of . On the basis of summarizing the pharmacological and pharmacokinetic studies of CA in recent years, we hope to provide useful information for CA about treating different diseases and to make suggestions for future research.: We collected relevant information (January 2014 to March 2020) on CA via the Internet database. Keywords searched includ pharmacology, pharmacokinetics and toxicology, and the number of effective references was 118. CA is a phytoestrogen with wide range of pharmacological activities. By affecting PI3K/Akt/mTOR, WDR7-7-GPR30, Rab27B-β-catenin-VEGF, etc. signaling pathway, CA showed the effect of anticancer, anti-inflammatory, anti-osteoporosis, neuroprotection, hepatoprotection, etc. Therefore, CA is prospective to be used in the treatment of many diseases.: Research shows that CA has a therapeutic effect on a variety of diseases. We think CA is a promising natural medicine. Therefore, we propose that the research directions of CA in the future include the following. Carrying out clinical research trials in order to find the most suitable medicinal concentration for different diseases; Exploring the synergistic mechanism of CA in combination with other drugs; Exploring ways to increase the blood circulation concentration of CA.
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http://dx.doi.org/10.1080/14787210.2021.1863145DOI Listing
December 2020

Lupeol and its derivatives as anticancer and anti-inflammatory agents: Molecular mechanisms and therapeutic efficacy.

Pharmacol Res 2021 02 11;164:105373. Epub 2020 Dec 11.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China. Electronic address:

Lupeol is a natural triterpenoid that widely exists in edible fruits and vegetables, and medicinal plants. In the last decade, a plethora of studies on the pharmacological activities of lupeol have been conducted and have demonstrated that lupeol possesses an extensive range of pharmacological activities such as anticancer, antioxidant, anti-inflammatory, and antimicrobial activities. Pharmacokinetic studies have indicated that absorption of lupeol by animals was rapid despite its nonpolar characteristics, and lupeol belongs to class II BCS (biopharmaceutics classification system) compounds. Moreover, the bioactivities of some isolated or synthesized lupeol derivatives have been investigated, and these results showed that, with modification to C-3 or C-19, some derivatives exhibit stronger activities, e.g., antiprotozoal or anticancer activity. This review aims to summarize the advances in pharmacological and pharmacokinetic studies of lupeol in the last decade with an emphasis on its anticancer and anti-inflammatory activities, as well as the research progress of lupeol derivatives thus far, to provide researchers with the latest information, point out the limitations of relevant research at the current stage and the aspects that should be strengthened in future research.
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http://dx.doi.org/10.1016/j.phrs.2020.105373DOI Listing
February 2021

Design and Characterisation of a Randomized Food Intervention That Mimics Exposure to a Typical UK Diet to Provide Urine Samples for Identification and Validation of Metabolite Biomarkers of Food Intake.

Front Nutr 2020 21;7:561010. Epub 2020 Oct 21.

Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom.

Poor dietary choices are major risk factors for obesity and non-communicable diseases, which places an increasing burden on healthcare systems worldwide. To monitor the effectiveness of healthy eating guidelines and strategies, there is a need for objective measures of dietary intake in community settings. Metabolites derived from specific foods present in urine samples can provide objective biomarkers of food intake (BFIs). Whilst the majority of biomarker discovery/validation studies have investigated potential biomarkers for single foods only, this study considered the whole diet by using menus that delivered a wide range of foods in meals that emulated conventional UK eating patterns. Fifty-one healthy participants (range 19-77 years; 57% female) followed a uniquely designed, randomized controlled dietary intervention, and provided spot urine samples suitable for discovery of BFIs within a real-world context. Free-living participants prepared and consumed all foods and drinks in their own homes and were asked to follow the protocols for meal consumption and home urine sample collection. This study also assessed the robustness, and impact on data quality, of a minimally invasive urine collection protocol. Overall the study design was well-accepted by participants and concluded successfully without any drop outs. Compliance for urine collection, adherence to menu plans, and observance of recommended meal timings, was shown to be very high. Metabolome analysis using mass spectrometry coupled with data mining demonstrated that the study protocol was well-suited for BFI discovery and validation. Novel, putative biomarkers for an extended range of foods were identified including legumes, curry, strongly-heated products, and artificially sweetened, low calorie beverages. In conclusion, aspects of this study design would help to overcome several current challenges in the development of BFI technology. One specific attribute was the examination of BFI generalizability across related food groups and across different preparations and cooking methods of foods. Furthermore, the collection of urine samples at multiple time points helped to determine which spot sample was optimal for identification and validation of BFIs in free-living individuals. A further valuable design feature centered on the comprehensiveness of the menu design which allowed the testing of biomarker specificity within a biobank of urine samples.
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http://dx.doi.org/10.3389/fnut.2020.561010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609501PMC
October 2020

Diet-Associated Inflammation Modulates Inflammation and WNT Signaling in the Rectal Mucosa, and the Response to Supplementation with Dietary Fiber.

Cancer Prev Res (Phila) 2021 Mar 28;14(3):337-346. Epub 2020 Oct 28.

Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.

Inflammation drives colorectal cancer development, and colorectal cancer risk is influenced by dietary factors, including dietary fiber. Hyperactive WNT signaling occurs in colorectal cancer and may regulate inflammation. This study investigated (i) relationships between the inflammatory potential of diet, assessed using the Energy-adjusted Dietary Inflammatory Index (E-DII), and markers of WNT signaling, and (ii) whether DII status modulated the response to supplementation with two types of dietary fiber. Seventy-five healthy participants were supplemented with resistant starch and/or polydextrose (PD) or placebo for 50 days. Rectal biopsies were collected before and after intervention and used to assess WNT pathway gene expression and crypt cell proliferation. E-DII scores were calculated from food frequency questionnaire data. High-sensitivity C-reactive protein (hsCRP) and fecal calprotectin concentrations were quantified. hsCRP concentration was significantly greater in participants with higher E-DII scores [least square means (LSM) 4.7 vs. 2.4 mg/L, = 0.03]. Baseline E-DII score correlated with ( = 0.503, = 0.003) and ( = 0.472, = 0.006) expression, after adjusting for age, gender, body mass index, endoscopy procedure, and smoking status. expression was more than 2-fold greater in individuals with higher E-DII scores (LSM 0.131 vs. 0.059, = 0.002). Baseline E-DII modulated the effects of PD supplementation on expression ( = 0.04). More proinflammatory diets were associated with altered WNT signaling and appeared to modulate the effects of PD supplementation on expression of This is the first study to investigate relationships between the E-DII and molecular markers of WNT signaling in rectal tissue of healthy individuals. Our finding that more inflammatory dietary components may impact large bowel health through effects on a well-recognized pathway involved in cancer development will strengthen the evidence base for dietary advice to help prevent bowel cancer.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0335DOI Listing
March 2021

Proteomic analysis demonstrates that parthenogenetically activated swamp buffalo embryos have dysregulated energy metabolism.

Reprod Domest Anim 2020 Dec 5;55(12):1764-1773. Epub 2020 Nov 5.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi University, Nanning, China.

The comprehensive understanding of early embryo development is essential to optimize in vitro culture conditions. Protein expression landscape of parthenogenetically produced embryo remains unexplored. This study aimed to investigate the protein expression dynamics with a particular focus on energy metabolism throughout the early developmental stages of parthenogenetic buffalo embryos. For this purpose, we performed iTRAQ-based quantitative mass spectrometry and identified 280 proteins common in all stages. A total of 933 proteins were identified during the proteomics analysis. The data depicted that morula and blastocyst had distinct protein expression dynamics as compared to 2- to 16-cell-stage embryo. KEGG pathway analysis showed 23 proteins belonging to energy metabolism appeared in the data. Study of energy metabolism-related protein's expression pattern demonstrated that there was asynchrony in proteins related to glycolysis throughout the examined developmental stages. The expression pattern of pyruvate kinase mutase (PKM), an essential protein of glycolysis, indicated a slightly decreasing trend from 2-cell-stage embryo to blastocyst, and it was supported by expression of proteins involved in lactate production (LDHA and LDHB) suggesting the decreasing rate of aerobic glycolysis (Warburg Effect) at morula and blastocyst stage. The increased Warburg Effect is considered as the hallmark of proliferating cells or embryo at the blastocyst stage. Furthermore, the proteins involved in the citric acid cycle also showed down-regulation at the blastocyst stage, indicating a lesser role of oxidative phosphorylation at this stage. Therefore, it could be divulged from the study that there may be an irregular pattern of energy metabolism in early parthenogenetic embryos. Further studies are recommended to understand this phenomenon.
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http://dx.doi.org/10.1111/rda.13838DOI Listing
December 2020

Applications, phytochemistry, pharmacological effects, pharmacokinetics, toxicity of Georgi. and its probably potential therapeutic effects on COVID-19: a review.

Chin Med 2020 25;15:102. Epub 2020 Sep 25.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu, 611137 China.

Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB's toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB's active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.
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http://dx.doi.org/10.1186/s13020-020-00384-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517065PMC
September 2020

Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease.

Hum Brain Mapp 2020 11 26;41(16):4704-4717. Epub 2020 Aug 26.

Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

A major focus of Alzheimer's disease (AD) research has been finding sensitive outcome measures to disease progression in preclinical AD, as intervention studies begin to target this population. We hypothesize that tailored measures of longitudinal change of the medial temporal lobe (MTL) subregions (the sites of earliest cortical tangle pathology) are more sensitive to disease progression in preclinical AD compared to standard cognitive and plasma NfL measures. Longitudinal T1-weighted MRI of 337 participants were included, divided into amyloid-β negative (Aβ-) controls, cerebral spinal fluid p-tau positive (T+) and negative (T-) preclinical AD (Aβ+ controls), and early prodromal AD. Anterior/posterior hippocampus, entorhinal cortex, Brodmann areas (BA) 35 and 36, and parahippocampal cortex were segmented in baseline MRI using a novel pipeline. Unbiased change rates of subregions were estimated using MRI scans within a 2-year-follow-up period. Experimental results showed that longitudinal atrophy rates of all MTL subregions were significantly higher for T+ preclinical AD and early prodromal AD than controls, but not for T- preclinical AD. Posterior hippocampus and BA35 demonstrated the largest group differences among hippocampus and MTL cortex respectively. None of the cross-sectional MTL measures, longitudinal cognitive measures (PACC, ADAS-Cog) and cross-sectional or longitudinal plasma NfL reached significance in preclinical AD. In conclusion, longitudinal atrophy measurements reflect active neurodegeneration and thus are more directly linked to active disease progression than cross-sectional measurements. Moreover, accelerated atrophy in preclinical AD seems to occur only in the presence of concomitant tau pathology. The proposed longitudinal measurements may serve as efficient outcome measures in clinical trials.
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http://dx.doi.org/10.1002/hbm.25151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555086PMC
November 2020

SCF-FBXO24 regulates cell proliferation by mediating ubiquitination and degradation of PRMT6.

Biochem Biophys Res Commun 2020 09 29;530(1):75-81. Epub 2020 Jul 29.

College of Life Science and Technology, Jinan University, Guangzhou, 510630, China; Institute of Biomedicine & National Engineering Research Center of Genetic Medicine, Guangzhou, 510630, China. Electronic address:

The protein arginine methyltransferase 6 (PRMT6) is a coregulator of gene expression by methylation of the histone H3 on arginine 2 (H3R2), H4R3 and H2AR3 [1,2]. PRMT6 is aberrantly expressed in various types of human cancer, and abnormal methylation in cancers caused by overexpression of PRMT6 is considered to correlate with poor recovery prognosis [3,4]. However, mechanisms that regulate PRMT6 protein stability in cells remain largely unknown. Here we identified that an orphan F-box protein, FBXO24, that binds to 270 to 275 amino acid residues of PRMT6 to cause polyubiquitination of lysine at position 369 of PRMT6, which mediates its degradation via the ubiquitin-proteasome pathway. Overexpression of FBXO24 or knockout of PRMT6 was found to inhibit cell proliferation, migration, and invasion in H1299 cells. PRMT6 K369R mutant became resistant to degradation. Overexpression of PRMT6 K369R caused cell cycle progression, resulting in cell proliferation. Thus, our data confirm that FBXO24 regulates cell proliferation by mediating ubiquitin-dependent proteasomal degradation of PRMT6.
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http://dx.doi.org/10.1016/j.bbrc.2020.06.007DOI Listing
September 2020

Complement modulation reverses pathology in Y402H-retinal pigment epithelium cell model of age-related macular degeneration by restoring lysosomal function.

Stem Cells Transl Med 2020 12 20;9(12):1585-1603. Epub 2020 Aug 20.

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

Age-related macular degeneration (AMD) is a multifactorial disease, which is characterized by loss of central vision, affecting one in three people by the age of 75. The Y402H polymorphism in the complement factor H (CFH) gene significantly increases the risk of AMD. We show that Y402H-AMD-patient-specific retinal pigment epithelium (RPE) cells are characterized by a significant reduction in the number of melanosomes, an increased number of swollen lysosome-like-vesicles with fragile membranes, Cathepsin D leakage into drusen-like deposits and reduced lysosomal function. The turnover of C3 is increased significantly in high-risk RPE cells, resulting in higher internalization and deposition of the terminal complement complex C5b-9 at the lysosomes. Inhibition of C3 processing via the compstatin analogue Cp40 reverses the disease phenotypes by relieving the lysosomes of their overburden and restoring their function. These findings suggest that modulation of the complement system represents a useful therapeutic approach for AMD patients associated with complement dysregulation.
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http://dx.doi.org/10.1002/sctm.20-0211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695639PMC
December 2020

Characteristic changes of traumatic dental injuries in a teaching hospital of Wuhan under transmission control measures during the COVID-19 epidemic.

Dent Traumatol 2020 Dec 8;36(6):584-589. Epub 2020 Sep 8.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and the Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Background/aims: In December 2019, a novel coronavirus emerged in Wuhan City, and a retrospective analysis is necessary to provide clinicians with the characteristics of traumatic dental injuries (TDIs) during the epidemic. The aim of this study was to evaluate the changes in the characteristics of TDIs under the transmission control measures in Wuhan City utilizing an epidemiologic investigation.

Materials And Method: In this retrospective study, epidemiologic information, including the number of patients, gender, age, and TDI parameters such as time since injury to the clinic visit, etiology, tooth location, and the type of injury was extracted from the records of patients in the hospital from two periods: period 1 (between January 23, 2020, and April 7, 2020) and period 2 (between January 23, 2019, and April 7, 2019). The data from the two periods were compared and analyzed.

Result: A total of 158 patients were treated for TDIs (120 in 2019 and 38 in 2020). Males were more likely to suffer from TDIs than females with a ratio of 1.5:1, both in 2020 and 2019. Other than that, there were characteristic changes in TDIs during the transmission control measures in the COVID-19 epidemic, which included the number of patients, age, time since injury to the clinic visit, etiology, tooth location and the type of TDI.

Conclusion: The transmission control measures during the COVID-19 epidemic had a significant impact on the epidemiology and etiology of TDIs in Wuhan City.
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http://dx.doi.org/10.1111/edt.12589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436214PMC
December 2020

Evodiamine: A review of its pharmacology, toxicity, pharmacokinetics and preparation researches.

J Ethnopharmacol 2020 Nov 30;262:113164. Epub 2020 Jul 30.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China. Electronic address:

Ethnopharmacological Relevance: Evodia rutaecarpa, a well-known herb medicine in China, is extensively applied in traditional Chinese medicine (TCM). The plant has the effects of dispersing cold and relieving pain, arresting vomiting, and helping Yang and stopping diarrhea. Modern research demonstrates that evodiamine, the main component of Evodia rutaecarpa, is the material basis for its efficacy.

Aims Of The Review: This paper is primarily addressed to summarize the current studies on evodiamine. The progress in research on the pharmacology, toxicology, pharmacokinetics, preparation researches and clinical application are reviewed. Moreover, outlooks and directions for possible future studies concerning it are also discussed.

Materials And Methods: The information of this systematic review was conducted with resources of multiple literature databases including PubMed, Google scholar, Web of Science and Wiley Online Library and so on, with employing a combination of keywords including "pharmacology", "toxicology", "pharmacokinetics" and "clinical application", etc. RESULTS: As the main component of Evodia rutaecarpa, evodiamine shows considerable pharmacological activities, such as analgesic, anti-inflammatory, anti-tumor, anti-microbial, heart protection and metabolic disease regulation. However, it is also found that it has significant hepatotoxicity and cardiotoxicity, thereby it should be monitored in clinical. In addition, available data demonstrate that the evodiamine has a needy solubility in aqueous medium. Scientific and reasonable pharmaceutical strategies should be introduced to improve the above defects. Meanwhile, more efforts should be made to develop novel efficient and low toxic derivatives.

Conclusions: This review summarizes the results from current studies of evodiamine, which is one of the valuable medicinal ingredients from Evodia rutaecarpa. With the assistance of relevant pharmacological investigation, some conventional application and problems in pharmaceutical field have been researched in recent years. In addition, unresolved issues include toxic mechanisms, pharmacokinetics, novel pharmaceutical researches and relationship between residues and intestinal environment, which are still being explored and excavate before achieving integration into clinical practice.
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http://dx.doi.org/10.1016/j.jep.2020.113164DOI Listing
November 2020

A Survey on HIV/AIDS-Related Knowledge, Attitudes, Risk Behaviors, and Characteristics of Men Who Have Sex with Men among University Students in Guangxi, China.

Biomed Res Int 2020 14;2020:7857231. Epub 2020 Jun 14.

Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning, Guangxi 530021, China.

In recent years, the prevalence of human immunodeficiency virus (HIV) infection among Chinese university students has increased significantly, and HIV transmission among men who have sex with men (MSM) comprises more than half of the new cases. There is still a lack of research investigating the incidence of male-to-male sex, the attitudes towards MSM, and the awareness of HIV/AIDS among university students in Guangxi, one of the HIV high-risk areas in China. Therefore, we performed a cross-sectional investigation among 578 male students, recruited by stratified sampling, in universities in Nanning, Guangxi, between January 2016 and March 2017. Researcher-administered anonymous questionnaires were completed. Self-recognition as MSM was found in 8.48% of the subjects. Compared with non-MSM, university student MSM included more people over the age of 20 (OR = 4.95), had less migration from other districts of Guangxi (OR = 0.26), and the majority were nonmedical students (OR = 8.99). In total, 63.25% of the male student participants reported a lack of acceptance of MSM, while 35.47% acknowledged barriers between themselves and acquaintances who were MSM. Overall, 67.30% of the subjects correctly answered questions related to AIDS knowledge. The proportion of MSM subjects who answered the AIDS-related questions completely correctly was significantly lower than that of non-MSM subjects (42.86% vs. 69. 57%, respectively, OR: 0.33), but the self-recognition risk of MSM was significantly higher than that of non-MSM (OR = 2.59). Risky behaviors associated with HIV infections, including smoking, alcohol consumption, drug abuse, and inconsistent condom use, were significantly higher among the MSM participants. The percentages of student's willingness to accept MC and PrEP were 70.93% and 77.51%, respectively. These results raise the alarm that university student MSM in Guangxi, China, require urgent public attention and more effective health education, including the education on MC and PrEP.
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http://dx.doi.org/10.1155/2020/7857231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312710PMC
March 2021

Neural and behavioral correlates of episodic memory are associated with temporal discounting in older adults.

Neuropsychologia 2020 09 2;146:107549. Epub 2020 Jul 2.

Department of Psychology, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address:

When facing decisions involving trade-offs between smaller, sooner and larger, delayed rewards, people tend to discount the value of future rewards. There are substantial individual differences in this tendency toward temporal discounting, however. One neurocognitive system that may underlie these individual differences is episodic memory, given the overlap in the neural circuitry involved in imagining the future and remembering the past. Here we tested this hypothesis in older adults, including both those that were cognitively normal and those with amnestic mild cognitive impairment (MCI). We found that performance on neuropsychological measures of episodic memory retrieval was associated with temporal discounting, such that people with better memory discounted delayed rewards less. This relationship was specific to episodic memory and temporal discounting, since executive function (another cognitive ability) was unrelated to temporal discounting, and episodic memory was unrelated to risk tolerance (another decision-making preference). We also examined cortical thickness and volume in medial temporal lobe regions critical for episodic memory. Entorhinal cortical thickness was associated with reduced temporal discounting, with episodic memory performance partially mediating this association. The inclusion of MCI participants was critical to revealing these associations between episodic memory and entorhinal cortical thickness and temporal discounting. These effects were larger in the MCI group, reduced after controlling for MCI status, and statistically significant only when including MCI participants in analyses. Overall, these findings suggest that individual differences in temporal discounting are driven by episodic memory function, and that a decline in medial temporal lobe structural integrity may impact temporal discounting.
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http://dx.doi.org/10.1016/j.neuropsychologia.2020.107549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502478PMC
September 2020

Seasonality and photoperiod influence in vitro production of buffalo embryos.

Reprod Domest Anim 2020 Sep 28;55(9):1115-1123. Epub 2020 Jul 28.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China.

Buffalo is considered short-day breeder in tropical and subtropical part of the world and seasonality and photoperiodism impart major influence on its fertility. However, its impact on in vitro embryo production (IVEP) remains elusive. Therefore, this study investigated the effect of seasonal variations and photoperiodism on morphological and molecular parameters of IVEP in buffalo. For this purpose, we conducted two different experiments on the oocytes obtained by aspirating follicles from abattoir derived ovaries. In Exp. I, retrospective analysis was performed for oocyte recovery, blastocyst and hatching rate, during four consecutive seasonal periods (i.e. January-March, April-June, July-September and October-December). In Exp. II, oocytes from peak breeding and non-breeding seasons were subjected to 24 hr in vitro maturation and evaluated for polar body extrusion to assess maturation rate. Results showed that embryo development was markedly low during second quarter (April-June) and maximum during fourth quarter (October-December) of the year; referred as non-breeding and breeding seasons, respectively. Comparative data analysis demonstrated that poor oocyte quality is major reason for lesser efficiency of embryo production during non-breeding season than peak breeding season as suggested by poor oocyte recovery (2.31 ± 0.10 vs. 3.65 ± 0.27) and maturation rate (33.32 ± 2.1 vs. 63.15 ± 7.31). Subsequently, comparative gene expression analysis of blastocysts during peak breeding season significantly upregulated pluripotency gene (OCT-4) and downregulated heat shock protein 90, as compared to non-breeding season. Therefore, it could be divulged from the present study that seasonal variations and photoperiodism have profound effect on oocyte quality and subsequent embryo development. It is recommended to find suitable additives for in vitro maturation that could mitigate seasonal effects.
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http://dx.doi.org/10.1111/rda.13749DOI Listing
September 2020

Developing community-based urine sampling methods to deploy biomarker technology for the assessment of dietary exposure.

Public Health Nutr 2020 12 11;23(17):3081-3092. Epub 2020 Jun 11.

Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, AberystwythSY23 3DA, UK.

Objective: Obtaining objective, dietary exposure information from individuals is challenging because of the complexity of food consumption patterns and the limitations of self-reporting tools (e.g., FFQ and diet diaries). This hinders research efforts to associate intakes of specific foods or eating patterns with population health outcomes.

Design: Dietary exposure can be assessed by the measurement of food-derived chemicals in urine samples. We aimed to develop methodologies for urine collection that minimised impact on the day-to-day activities of participants but also yielded samples that were data-rich in terms of targeted biomarker measurements.

Setting: Urine collection methodologies were developed within home settings.

Participants: Different cohorts of free-living volunteers.

Results: Home collection of urine samples using vacuum transfer technology was deemed highly acceptable by volunteers. Statistical analysis of both metabolome and selected dietary exposure biomarkers in spot urine collected and stored using this method showed that they were compositionally similar to urine collected using a standard method with immediate sample freezing. Even without chemical preservatives, samples can be stored under different temperature regimes without any significant impact on the overall urine composition or concentration of forty-six exemplar dietary exposure biomarkers. Importantly, the samples could be posted directly to analytical facilities, without the need for refrigerated transport and involvement of clinical professionals.

Conclusions: This urine sampling methodology appears to be suitable for routine use and may provide a scalable, cost-effective means to collect urine samples and to assess diet in epidemiological studies.
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http://dx.doi.org/10.1017/S136898002000097XDOI Listing
December 2020

Diffeomorphic Medial Modeling.

Inf Process Med Imaging 2019 Jun 22;11492:208-220. Epub 2019 May 22.

Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA.

Deformable shape modeling approaches that describe objects in terms of their geometry (e.g., [10]) yield rich geometrical features that can be useful for analyzing the shape of sheet-like biological structures, such as the myocardium. We present a novel shape analysis approach that combines the benefits of medial shape modeling and diffeomorphometry. Our algorithm is formulated as a problem of matching shapes using diffeomorphic flows under constraints that approximately preserve medial axis geometry during deformation. As the result, correspondence between the medial axes of similar shapes is maintained. The approach is evaluated in the context of modeling the shape of the left ventricular wall from 3D echocardiography images.
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http://dx.doi.org/10.1007/978-3-030-20351-1_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222280PMC
June 2019

Tea saponins as natural stabilizers for the production of hesperidin nanosuspensions.

Int J Pharm 2020 Jun 5;583:119406. Epub 2020 May 5.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, PR China. Electronic address:

Tea saponins (TS), a novel multifunctional stabilizer, were explored to stabilize the nanosuspensions. The purpose of this study was to investigate the effect of TS on the stability and redispersibility of nanosuspensions. In present work, hesperidin (HDN), a poorly soluble drug, was used as a model drug. HDN nanosuspensions (HDN-NS) with particle size of 250-270 nm were prepared by high-speed shearing and high-pressure homogenization. The zeta potential of HDN-NS was -23.16 ± 1.12 mV. Compared with traditional stabilizers, TS were superior in stabilization efficiency at low concentrations. Nanosuspensions freeze-dried powder using TS and lactose as cryoprotectants had good redispersibility, and the average particle size was 266.5 ± 9.0 nm after reconstitution. TS and lactose can effectively prevent the irreversible agglomeration of HDN-NS during freeze-drying. The dissolution was enhanced owing to particle size reduction. Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM) results showed that HDN nanocrystals were irregularly lumpy. The chemical structure and crystal state of HDN had not significantly changed during production. In conclusion, TS have the potential to stabilize and disperse nanosuspensions and provide a promising strategy for the development of poorly soluble drugs.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119406DOI Listing
June 2020

Imperatorin: A review of its pharmacology, toxicity and pharmacokinetics.

Eur J Pharmacol 2020 Jul 24;879:173124. Epub 2020 Apr 24.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China. Electronic address:

As a naturally occurring furanocoumarin, the medicinal value of imperatorin has been studied more and more. We hope to provide useful information for the further development of imperatorin by analyzing the literature of imperatorin in recent years. By collating the literature on the pharmacology of imperatorin, we found that the pharmacological activity of imperatorin is wide and imperatorin can be used for anti-cancer, neuroprotection, anti-inflammatory, anti-hypertension and antibacterial. In addition, we found that some researchers confirmed the toxicity of imperatorin. Pharmacokinetic studies demonstrated that oxidation metabolism is the main metabolic pathways of imperatorin. At present, the shortcomings of research on imperatorin mainly include: most pharmacological studies are concentrated in vitro, lacking enough in vivo experimental data; more and more studies showed that imperatorin has synergistic effect with other drugs in anticancer and other aspects, but lacking the detailed explanation of the mechanism of the synergistic effect; imperatorin has side effect, but it lacks enough experimental conclusions. Based on the above defects, we believe that more in vivo experiments of imperatorin should be carried out in the future; future research need to explore synergistic mechanisms of imperatorin with other drugs, especially in anticancer; the dose affects both the pharmacological activity and the side effect of imperatorin. The relationship between the dose and the two aspects need to be further studied in order to reduce the side effect. In addition, through structural modification of imperatorin, it is possible to improve the treatment effect and reduce side effect.
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http://dx.doi.org/10.1016/j.ejphar.2020.173124DOI Listing
July 2020

Contribution of mixed pathology to medial temporal lobe atrophy in Alzheimer's disease.

Alzheimers Dement 2020 06 22;16(6):843-852. Epub 2020 Apr 22.

Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Introduction: It is unclear how different proteinopathies (tau, transactive response DNA-binding protein 43 [TDP-43], amyloid β [Aβ], and α-synuclein) contribute to atrophy within medial temporal lobe (MTL) subregions in Alzheimer's disease (AD).

Methods: We utilized antemortem structural magnetic resonance imaging (MRI) data to measure MTL substructures and examined the relative contribution of tau, TDP-43, Aβ, and α-synuclein measured in post-mortem tissue from 92 individuals with intermediate to high AD neuropathology. Receiver-operating characteristic (ROC) curves were analyzed for each subregion in order to discriminate TDP-43-negative and TDP-43-positive patients.

Results: TDP-43 was strongly associated with anterior MTL regions, whereas tau was relatively more associated with the posterior hippocampus. Among the MTL regions, the anterior hippocampus showed the highest area under the ROC curve (AUC).

Discussion: We found specific contributions of different pathologies on MTL substructure in this population with AD neuropathology. The anterior hippocampus may be a relevant region to detect concomitant TDP-43 pathology in the MTL of patients with AD.
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http://dx.doi.org/10.1002/alz.12079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715004PMC
June 2020

Resistant starch supplementation increases crypt cell proliferative state in the rectal mucosa of older healthy participants.

Br J Nutr 2020 08 13;124(4):374-385. Epub 2020 Apr 13.

Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon TyneNE2 4HH, UK.

There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.
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http://dx.doi.org/10.1017/S0007114520001312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369377PMC
August 2020

Artificial Intelligence System Approaching Neuroradiologist-level Differential Diagnosis Accuracy at Brain MRI.

Radiology 2020 06 7;295(3):626-637. Epub 2020 Apr 7.

From the Department of Radiology & Biomedical Imaging, University of California, San Francisco, 513 Parnassus Ave, Room S-261, Box 0628, San Francisco, CA 94143-0628 (A.M.R.); Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104 (A.M.R., J.D.R., L.X., J.W., M.T.D., A.M.K., J.E., T.C.C., I.M.N., S.M., J.C.G.); Mecklenburg Radiology Associates, Charlotte, NC (E.J.B.); and Department of Radiology, University of Texas at Austin, Austin, TX (R.N.B.).

Background Although artificial intelligence (AI) shows promise across many aspects of radiology, the use of AI to create differential diagnoses for rare and common diseases at brain MRI has not been demonstrated. Purpose To evaluate an AI system for generation of differential diagnoses at brain MRI compared with radiologists. Materials and Methods This retrospective study tested performance of an AI system for probabilistic diagnosis in patients with 19 common and rare diagnoses at brain MRI acquired between January 2008 and January 2018. The AI system combines data-driven and domain-expertise methodologies, including deep learning and Bayesian networks. First, lesions were detected by using deep learning. Then, 18 quantitative imaging features were extracted by using atlas-based coregistration and segmentation. Third, these image features were combined with five clinical features by using Bayesian inference to develop probability-ranked differential diagnoses. Quantitative feature extraction algorithms and conditional probabilities were fine-tuned on a training set of 86 patients (mean age, 49 years ± 16 [standard deviation]; 53 women). Accuracy was compared with radiology residents, general radiologists, neuroradiology fellows, and academic neuroradiologists by using accuracy of top one, top two, and top three differential diagnoses in 92 independent test set patients (mean age, 47 years ± 18; 52 women). Results For accuracy of top three differential diagnoses, the AI system (91% correct) performed similarly to academic neuroradiologists (86% correct; = .20), and better than radiology residents (56%; < .001), general radiologists (57%; < .001), and neuroradiology fellows (77%; = .003). The performance of the AI system was not affected by disease prevalence (93% accuracy for common vs 85% for rare diseases; = .26). Radiologists were more accurate at diagnosing common versus rare diagnoses (78% vs 47% across all radiologists; < .001). Conclusion An artificial intelligence system for brain MRI approached overall top one, top two, and top three differential diagnoses accuracy of neuroradiologists and exceeded that of less-specialized radiologists. © RSNA, 2020 See also the editorial by Zaharchuk in this issue.
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http://dx.doi.org/10.1148/radiol.2020190283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263320PMC
June 2020