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1.
Neuroscience ; 523: 7-19, 2023 07 15.
Article in English | MEDLINE | ID: mdl-37225050

ABSTRACT

Ginkgo biloba L. leaf extract (GBE) has been added in many commercial herbal formulations such as EGb 761 and Shuxuening Injection to treat cardiovascular diseases and stroke worldwide. However, the comprehensive effects of GBE on cerebral ischemia remained unclear. Using a novel GBE (nGBE), which consists of all the compounds of traditional (t)GBE and one new compound, pinitol, we investigated its effect on inflammation, white matter integrity, and long-term neurological function in an experimental stroke model. Both transient middle cerebral artery occlusion (MCAO) and distal MCAO were conducted in male C57/BL6 mice. We found that nGBE significantly reduced infarct volume at 1, 3, and 14 days after ischemia. Sensorimotor and cognitive functions were superior in nGBE treated mice after MCAO. nGBE inhibited the release of IL-1ß in the brain, promoted microglial ramification, and regulated the microglial M1 to M2 phenotype shift at 7 days post injury. In vitro analyses showed that nGBE treatment reduced the production of IL-1ß and TNFα in primary microglia. Administration of nGBE also decreased the SMI-32/MBP ratio and enhanced myelin integrity, thus exhibiting improved white matter integrity at 28 days post stroke. These findings demonstrate that nGBE protects against cerebral ischemia by inhibiting microglia-related inflammation and promoting white matter repair, suggesting that nGBE is a promising therapeutic strategy for long-term recovery after stroke.


Subject(s)
Brain Ischemia , Stroke , White Matter , Mice , Male , Animals , Ginkgo biloba , Neuroinflammatory Diseases , Stroke/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Brain Ischemia/drug therapy , Infarction, Middle Cerebral Artery/drug therapy , Microglia , Inflammation/drug therapy
2.
Front Endocrinol (Lausanne) ; 13: 899575, 2022.
Article in English | MEDLINE | ID: mdl-35784558

ABSTRACT

The thyroid imaging reporting and data system (TIRADS) was proposed by experts for optimal ultrasound evaluation of malignancy risk of thyroid focal lesions. There are several versions of TIRADS, some of them have been validated sufficiently, and the others have not been well assessed. In this study, a recently launched Chinese version of TIRADS (C-TIRADS) for malignancy risk stratification of thyroid nodules was validated, and the performance was compared to that of the Korean TIRADS (K-TIRADS) and American College of Radiology(ACR) TIRADS (ACR-TIRADS). Archives of 2177 patients who had undergone thyroid ultrasound examination, coarse needle tissue biopsy and/or surgery were reviewed, and 1978 patients with 1982 thyroid nodules were assessed according to the three TIRADSs. The histopathology was taken as the golden standard. The results showed the 1982 thyroid nodules were consisted of 1306 benign nodules and 676 malignant nodules. The malignancy risk accounted for 1.09%, 2.14%, 10.34%, 49.28%, 88.19% and 85.29% of the total nodules that were categorised as C-TIRADS 2, 3, 4A, 4B, 4C and 5, respectively; 0.00%, 1.64%, 2.87%,18.71% and 82.22% of the total nodules that were categorised as ACR-TIRADS 1, 2, 3, 4 and 5, respectively; 0.85%, 3.27%, 24.27% and 80.96% of the total nodules that were categorised as K-TIRADS 2, 3, 4 and 5, respectively. The correlation between the category of TIRADS and percentile of malignancy was 0.94 in the C-TIRADS, 1.00 in the ACR-TIRADS, and 1.00 in the K-TIRADS, respectively. The highest values of accuracy(AUC) of ROC curves of C-TIRADS 4B, K-TIRADS 5 and ACR-TIRADS 5 were taken as the cut-off values for risk stratification, respectively. The sensitivity, specificity, positive and negative predictive values and AUC by C-TIRADS 4B, K-TIRADS 5 and ACR-TIRADS 5 for malignancy risk stratification of thyroid nodules were 90.83%, 84.23%, 74.88% and 94.66% and 0.88, respectively; 83.58%, 89.82%, 80.95%, 91.36% and 0.87, respectively; and 85.50%, 90.35%, 82.10%, 92.33% and 0.88, respectively (P>0.05 for all). We concluded that the C-TIRADS has excellent performance in the malignancy risk stratification of thyroid nodules by the optimized cut-off value, which is comparable to that in K-TIRADS and ACR-TIRADS.


Subject(s)
Thyroid Neoplasms , Thyroid Nodule , Humans , Risk Assessment/methods , Thyroid Neoplasms/pathology , Thyroid Nodule/pathology , Ultrasonography/methods
3.
Ann Transl Med ; 10(6): 283, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35433995

ABSTRACT

Background: Dual antiplatelet therapy with aspirin and clopidogrel (ASA + CPG) during the first 21 days has been shown to reduce the risk of major ischemic events in patients with transient ischemic attack (TIA) or minor stroke. However, the mechanisms underlying combination treatment with ASA + CPG in experimental ischemic stroke has not been fully elucidated. Methods: Minor cerebral ischemia was induced in mice by transient distal middle cerebral artery occlusion (tdMCAO). Two doses of ASA + CPG (12 and 24 mg/kg/day) or vehicle were administered by gavage daily. Neurological behaviors were assessed using the modified Garcia scores, Rotarod test, Y maze, and open field test. Platelet function was assessed in vitro by flow cytometry and in vivo by bleeding and clotting time. The neutrophil ratio and the levels of inflammatory cytokines were measured by flow cytometry and the Meso Scale Discovery (MSD) electrochemilunimescence, respectively. Results: Sensorimotor function was partially recovered with ASA + CPG treatment after ischemia. Anxiety levels and cognitive functions showed improvement in the ASA + CPG group at 12 mg/kg/day after 21 days. Both tail bleeding time and flow cytometry showed significantly decreased platelet function after ASA + CPG treatment. Notably, ASA + CPG at 12 mg/kg/day prolonged clotting time at 28 days after injury. Furthermore, the ratio of neutrophils, an indicator of inflammation, was reduced with 12 mg/kg/day ASA + CPG treatment in the bone marrow (BM) at 21 days and in the peripheral blood (PB) at 21 and 28 days after tdMCAO. Both doses of ASA + CPG decreased pro-inflammatory cytokine interleukin (IL)-6 expression 21 days after stroke. Taken together, these results demonstrated that combination treatment with ASA + CPG improved long-term neurological function after stroke and may inhibit platelet-neutrophil interaction by decreasing the concentration of pro-inflammatory cytokine, IL-6. Conclusions: These findings indicate a neuroprotective effect of combination treatment with ASA + CPG for a duration of 21 days in an experimental acute minor stroke model. These findings provide further evidence that dual antiplatelet therapy may be a viable neuroprotective treatment to decrease the recurrence of stroke.

4.
Ann Transl Med ; 10(4): 160, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35280366

ABSTRACT

Background: The function of IκB kinase α (IKKα) in the brain is largely unknown. This study examined the effects of IKKα on autophagy after cerebral ischemia. Methods: Permanent distal middle cerebral artery occlusion (dMCAO) was conducted in C57/BL6 mice. Oxygen-glucose deprivation/reperfusion (OGD/R) was performed to mimic ischemia injury in neuro-2A (N2A) cells in vitro. Autophagy activation was assessed by detecting the ratio of microtubule-associated protein 1 light chain 3ß (LC3B)-II/LC3B-I and Cyto-ID autophagic fluorescence. The infarct volume was verified by 2,3,5-triphenyltetrazolium chloride (TTC) staining and magnetic resonance imaging (MRI). Neurological functions were evaluated using the modified Garcia test. Cell death after dMCAO was confirmed with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. To determine the role of IKKα, small interfering RNA (siRNA) was transfected into N2A cells or injected intracerebroventricularly. Results: IKKα and LC3B II/I expression levels were increased both in OGD/R treated N2A cells and dMCAO mice. Under the same conditions, IKKß expression was not altered. IKKα siRNA significantly decreased the infarct volume and the apparent diffusion coefficient (ADC) related to brain edema, and promoted the neurological outcomes after dMCAO. Furthermore, inhibition of IKKα attenuated ischemia- induced the conversion of LC3B I to LC3B II both in vitro and in vivo. In addition, IKKα siRNA alleviated the formation of autophagic vacuoles and LC3 positive puncta after cerebral ischemia. Conclusions: These findings indicate that IKKα, but not IKKß, plays a critical role in ischemia-induced autophagy. Inhibition of IKKα protects the brain from ischemia injury and this may have potential benefits in stroke therapy.

5.
Math Biosci Eng ; 19(2): 1591-1608, 2022 01.
Article in English | MEDLINE | ID: mdl-35135219

ABSTRACT

Delineation of the boundaries of the Left Ventricle (LV) in cardiac Magnetic Resonance Images (MRI) is a hot topic due to its important diagnostic power. In this paper, an approach is proposed to extract the LV in a sequence of MR images. In the proposed paper, all images in the sequence are segmented simultaneously and the shape of the LV in each image is supposed to be similar to that of the LV in nearby images in the sequence. We coined the novel shape similarity constraint, and it is called sequential shape similarity (SSS in short). The proposed segmentation method takes the Active Contour Model as the base model and our previously proposed Gradient Vector Convolution (GVC) external force is also adopted. With the SSS constraint, the snake contour can accurately delineate the LV boundaries. We evaluate our method on two cardiac MRI datasets and the Mean Absolute Distance (MAD) metric and the Hausdorff Distance (HD) metric demonstrate that the proposed approach has good performance on segmenting the boundaries of the LV.


Subject(s)
Heart Ventricles , Heart , Algorithms , Heart/diagnostic imaging , Heart Ventricles/diagnostic imaging , Image Processing, Computer-Assisted , Magnetic Resonance Imaging/methods
6.
Neurochem Res ; 46(4): 755-769, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33389472

ABSTRACT

Cerebral ischemia leads to reactive astrogliosis and glial scar formation. Glial scarring can impede functional restoration during the recovery phase of stroke. Salidroside has been shown to have neuroprotective effects after ischemic stroke, but its impact on long-term neurological recovery, especially whether it regulates reactive astrogliosis and glial scar formation, is unclear. In this study, male adult C57/BL6 mice were subjected to transient cerebral ischemia injury followed by intravenous salidroside treatment. Primary astrocytes were treated with lipopolysaccharide (LPS) or conditioned medium from cultured primary neurons subjected to oxygen-glucose deprivation (CM-OGD). Salidroside significantly improved long-term functional outcomes following ischemic stroke in the rotarod and corner tests. It also reduced brain glial scar volume and decreased expression of the glial scar marker, glial fibrillary acidic protein (GFAP) and inhibited astrocyte proliferation. In primary astrocyte cultures, salidroside protected astrocytes from CM-OGD injury-induced reactive astroglial proliferation, increasing the percentage of cells in G0/G1 phase and reducing the S populations. The inhibitory effect of salidroside on the cell cycle was related to downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA expression and increased p27Kip1 mRNA expression. Similar results were found in the LPS-stimulated injury model in astroglial cultures. Western blot analysis demonstrated that salidroside attenuated the CM-OGD-induced upregulation of phosphorylated Akt and glycogen synthase kinase 3ß (GSK-3ß). Taken together, these results suggested that salidroside can inhibit reactive astrocyte proliferation, ameliorate glial scar formation and improve long-term recovery, probably through its effects on the Akt/GSK-3ß pathway.


Subject(s)
Brain Ischemia/drug therapy , Gliosis/drug therapy , Glucosides/therapeutic use , Neuroprotective Agents/therapeutic use , Phenols/therapeutic use , Signal Transduction/drug effects , Animals , Astrocytes/drug effects , Brain/pathology , Brain Ischemia/complications , Brain Ischemia/pathology , Cell Proliferation/drug effects , Gliosis/etiology , Gliosis/pathology , Glycogen Synthase Kinase 3 beta/metabolism , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/pathology , Male , Mice, Inbred C57BL , Proto-Oncogene Proteins c-akt/metabolism
7.
J Ultrason ; 20(82): e181-e184, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33365154

ABSTRACT

Aim: To investigate the validity of measurement of testicular volume acquired by a built-in software in different ultrasound systems with reference to the updated guidelines. Materials and methods: Archives of 1,976 patients who had undergone scrotal ultrasound evaluation were reviewed. A total of 973 patients with 1,909 testes, who had undergone ultrasound measurement of the testicular volume, were included in the study, and 1,003 patients were excluded. The age of enrolled patients ranged from 17 to 66 years (median age of 39 years). The ultrasound systems included Siemens Sonoline S2000, Philips EPIQ5, GE Logiq E9, Hitachi Aloka prosoundα7, Mindray DC-8 and Mindray Resona7. The transducers have imaging frequencies of 5-14 MHz. Validity of the measurement of testicular volume acquired by a built-in software in different ultrasound systems was assessed with reference to the formula that Volume (V) = Length (L) × Width (W) × Height (H) × 0.71, recommended by the updated guidelines, by recalculating the original numbers using a calculator. Results: The values obtained by the built-in software of Mindray DC-8 and Mindray Resona7 ultrasound systems and measurements recalculated on a computer were all in concordance; and the values obtained by the built-in software of Siemens Sonoline S2000, Philips EPIQ5, GE Logiq E9, and Hitachi Aloka prosoundα7 ultrasound systems and measurements recalculated on computer were all discordant. The same testicular measurements calculated with different formulas (V = L×W×H×0.71 vs. V = L×W×H×0.52) produced 26.76% difference. Conclusion: Values of testicular volume obtained by some ultrasound systems are not accurate with reference to the formula recommended by the updated guidelines.

8.
Sci Rep ; 10(1): 22028, 2020 12 16.
Article in English | MEDLINE | ID: mdl-33328507

ABSTRACT

The purpose of this study was to curate clustered findings of duplex ultrasound in the evaluation of spermatic venous varicoceles, and deliver more responses to the present concerns. Archives of 979 men who had undergone scrotum and spermatic venous plexus duplex ultrasound were reviewed. In the duplex ultrasound interrogation, the sizes of the larger vessels of the spermatic venous plexus, peritesticular vessels, and testicular volume and relevant parameters were measured. Findings of the vessels were analyzed. One hundred and eight-one out of 979 patients had varicoceles. Color Doppler flow signal was rendered in veins of pampiniform plexus but not in peritesticular vessels in 501 out of 979 patients; 101 out of 501 patients had veins of pampiniform plexus ≤ 3 mm, no color Doppler flow signal could be rendered in the veins in the 101 patients at supine and standing positions without Valsalva maneuver, color Doppler flow signal could be rendered in the veins in 82 out of 101 patients at supine and standing positions with Valsalva maneuver; no color Doppler flow signal could be rendered in the veins from 19 out of 101 patients with and without Valsalva maneuver at supine and standing positions. 37 out of 979 patients with 61 ipsilateral testicular volume ≤ 5 mL had no vessel diameter > 2 mm. The incidences of varicoceles corresponding to different ranges of testicular volume of 1-5 mL, 5.1-10 mL, 10.1-15 mL, 15.1-20 mL, 20.1-25 mL, and 25.1-30 mL were 0.0%, 6.9%, 8.3%, 6.63%, 20.94%, and 59.1%, respectively. The comparisons of incidences of varicocele between distribution percentages of different ranges of testicular volume of 1-5 mL and others (of 5.1 mL and more) were all significant (all P < 0.05). The correlation coefficient between the different ranges of testicular volume and the incidence of varicoceles was 0.829. Increased testicular volume may be also a factor for the development of varicoceles. Dilated peritesticular vessels may be collateral veins of spermatic veins, anterior and posterior scrotal veins, or proximal vas deferens.


Subject(s)
Scrotum/diagnostic imaging , Ultrasonography, Doppler, Duplex , Varicocele/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Organ Size , Scrotum/pathology , Testis/blood supply , Testis/diagnostic imaging , Testis/pathology , Varicocele/pathology , Young Adult
9.
Curr Res Transl Med ; 68(4): 197-203, 2020 11.
Article in English | MEDLINE | ID: mdl-32814684

ABSTRACT

The rigorous design of preclinical experimental studies of candidate neuroprotectants for the treatment of acute ischemic stroke is crucial for the success of subsequent randomized clinical trials. The efficacy of Ginkgo biloba extracts (GBEs) in complex mixtures for the treatment of acute ischemic stroke remains unclear. In this preclinical randomized controlled trail (pRCT), the effects of a novel (n)GBE containing pinitol versus traditional (t)GBE without pinitol were evaluated on the mouse models of acute transient and permanent stroke, separately. The sample size, an important aspect of study design, was calculated based on our experimental data. Mice with ischemia that were induced by transient middle cerebral artery occlusion (tMCAO) or permanent distal middle cerebral artery occlusion (pdMCAO), were treated with vehicle, nGBE, tGBE, or pinitol alone by tail-vein injection. Our results showed that nGBE significantly reduced infarct size in mice with tMCAO compared with vehicle-treated control mice. Both nGBE and tGBE significantly reduced infarct size in mice with pdMCAO compared with the vehicle-treated controls. None of the three treatments rescued weight loss or prevented the neurological deficits in either the tMCAO- or pdMCAO-model mice. These findings suggest that nGBE, which includes all of the components of tGBE and pinitol, is neuroprotective in two ischemic stroke models. Additional studies of complex GBE mixtures for stroke treatment compared to single component medications are undergoing evaluation.


Subject(s)
Brain Ischemia , Neuroprotective Agents , Plant Extracts , Stroke , Animals , Brain Ischemia/drug therapy , Ginkgo biloba , Mice , Neuroprotective Agents/therapeutic use , Plant Extracts/therapeutic use , Random Allocation , Stroke/drug therapy
10.
PLoS One ; 15(3): e0230581, 2020.
Article in English | MEDLINE | ID: mdl-32214376

ABSTRACT

The gradient vector flow (GVF) is an effective external force to deform the active contours. However, it suffers from high computational cost. For efficiency, the virtual electric field (VEF) model has been proposed, which can be implemented in real time thanks to fast Fourier transform (FFT). The VEF model has large capture range and low computation cost, but it has the limitations of sensitivity to noise and leakage on weak edge. The recently proposed CONVEF (Convolutional Virtual Electric Field) model takes the VEF model as a convolutional operation and employed another convolution kernel to overcome the drawbacks of the VEF model. In this paper, we employ an edge stopping function similar to that in the anisotropic diffusion to further improve the CONVEF model, and the proposed model is referred to as MCONVEF (Modified CONVEF) model. In addition, a piecewise constant approximation algorithm is borrowed to accelerate the calculation of the MCONVEF model. The proposed MCONVEF model is compared with the GVF and VEF models, and the experimental results are presented to demonstrate its superiority in terms of noise robustness, weak edge preserving and deep concavity convergence.


Subject(s)
Electricity , Models, Theoretical , Algorithms , Heart/diagnostic imaging , Humans , Image Processing, Computer-Assisted , Mediastinum/diagnostic imaging
11.
Stroke ; 49(9): 2211-2219, 2018 09.
Article in English | MEDLINE | ID: mdl-30354988

ABSTRACT

Background and Purpose- tPA (tissue-type plasminogen activator) is the only recommended intravenous thrombolytic agent for ischemic stroke. However, its application is limited because of increased risk of hemorrhagic transformation beyond the time window. T541 is a Chinese compound medicine with potential to attenuate ischemia and reperfusion injury. This study was to explore whether T541-benefited subjects underwent tPA thrombolysis extending the time window. Methods- Male C57BL/6 N mice were subjected to carotid artery thrombosis by stimulation with 10% FeCl3 followed by 10 mg/kg tPA with/without 20 mg/kg T541 intervention at 4.5 hours. Thrombolysis and cerebral blood flow were observed dynamically until 24 hours after drug treatment. Neurological deficit scores, brain edema and hemorrhage, cerebral microvascular junctions and basement membrane proteins, and energy metabolism in cortex were assessed then. An in vitro hypoxia/reoxygenation model using human cerebral microvascular endothelial cells was used to evaluate effect of T541 on tight junctions and F-actin in the presence of tPA. Results- tPA administered at 4.5 hours after carotid thrombosis resulted in a decrease in thrombus area and survival rate, whereas no benefit on cerebral blood flow. Study at 24 hours after tPA administration revealed a significant angioedema and hemorrhage in the ischemia hemisphere, a decreased expression of junction proteins claudin-5, zonula occludens-1, occludin, junctional adhesion molecule-1 and vascular endothelial cadherin, and collagen IV and laminin. Meanwhile, ADP/ATP, AMP/ATP, and ATP5D (ATP synthase subunit) expression and activities of mitochondria complex I, II, and IV declined, whereas malondialdehyde and 8-Oxo-2'-deoxyguanosine increased and F-actin arrangement disordered. All the insults after tPA treatment were attenuated by addition of T541 dose dependently. Conclusions- The results suggest T541 as a potential remedy to attenuate delayed tPA-related angioedema and hemorrhage and extend time window for tPA treatment. The potential of T541 to upregulate energy metabolism and protect blood-brain barrier is likely attributable to its effects observed.


Subject(s)
Alkenes/pharmacology , Brain Edema , Carotid Artery Thrombosis , Cerebrovascular Circulation/drug effects , Drugs, Chinese Herbal/pharmacology , Intracranial Hemorrhages , Polyphenols/pharmacology , Reperfusion Injury , Saponins/pharmacology , Animals , Antigens, CD/drug effects , Antigens, CD/metabolism , Astragalus Plant , Brain/blood supply , Brain/drug effects , Cadherins/drug effects , Cadherins/metabolism , Cell Adhesion Molecules/drug effects , Cell Adhesion Molecules/metabolism , Claudin-5/drug effects , Claudin-5/metabolism , Collagen Type IV/drug effects , Collagen Type IV/metabolism , Disease Models, Animal , Drug Combinations , Electron Transport Complex I , Electron Transport Complex II , Electron Transport Complex IV , Laminin/drug effects , Laminin/metabolism , Male , Mice , Occludin/drug effects , Occludin/metabolism , Panax notoginseng , Receptors, Cell Surface/drug effects , Receptors, Cell Surface/metabolism , Tissue Plasminogen Activator/pharmacology , Zonula Occludens-1 Protein/drug effects , Zonula Occludens-1 Protein/metabolism
12.
Front Physiol ; 9: 658, 2018.
Article in English | MEDLINE | ID: mdl-29910744

ABSTRACT

The purpose of the study was to explore the effect and the underlying mechanism of YangXue QingNao Wan (YXQNW) and Silibinin Capsules (SC), the two Chinese medicines, on cognitive impairment in older people with familial hyperlipidaemia. Fourteen month-old female LDLR (+/-) golden Syrian hamsters were used with their wild type as control. YXQNW (0.5 g/kg/day), SC (0.1 g/kg/day), or YXQNW (0.5 g/kg/day) + SC (0.1 g/kg/day) were administrated orally for 30 days. To assess the effects of the two drugs on plasma lipid content and cognitive ability, plasma TC, TG, LDL-C, and HDL-C were measured, and Y maze task was carried out both before and after administration. After administering of the drugs for 30 days, to evaluate the effect of the two drugs on disturbed blood flow caused by hyperlipidemia, the cerebral blood flow (CBF) was measured. To assess blood-brain barrier integrity, albumin leakage in middle cerebral artery (MCA) area was determined. To evaluate the effect of the drugs on impaired microvessels, the number and morphology of microvessels were assessed in hippocampus area. To further evaluate the ultrastructure of microvessels in hippocampus, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were carried out. To assess the profiles of claudin-5 and occludin in hippocampus, we performed immunofluorescence. Finally, to assess the expression of claudin-5, JAM-1, occludin and ZO-1 in hippocampus, western blot was carried out. The results showed that YXQNW, SC, and YXQNW + SC improved cognitive impairment of aged LDLR (+/-) golden Syrian hamsters without lowering plasma TC and LDL-C. YXQNW, SC, and YXQNW + SC attenuated albumin leakage in MCA area and neuronal damage in hippocampus, concomitant with an increase in CBF, a decrease of perivascular edema and an up-regulated expression of claudin-5, occludin and ZO-1. In conclusion, YXQNW, SC, and YXQNW + SC are able to improve cognitive ability in aged LDLR (+/-) golden Syrian hamsters via mechanisms involving maintaining blood-brain barrier integrity. These findings provide evidence suggesting YXQNW or SC as a potential regime to counteract the cognitive impairment caused by familial hypercholesterolemia.

13.
Drug Metab Dispos ; 45(5): 449-456, 2017 05.
Article in English | MEDLINE | ID: mdl-28209803

ABSTRACT

Emerging evidence indicates an important role for the breast cancer resistance protein (BCRP) in limiting brain penetration of substrate drugs. While in vitro transwell assays can provide an indication of BCRP substrate potential, the predictability of these assays in relation to in vivo brain penetration is still under debate. The present study examined the correlation of BCRP membrane protein expression level and transcellular transport activity across Madin-Darby canine kidney (MDCK) II monolayers. We expressed human BCRP or murine BCRP1 in MDCKII wild-type cells using BacMam2 virus transduction. The selective P-glycoprotein (P-gp) inhibitor LY335979 (1 µM) was included in the transport medium to measure BCRP-mediated transcellular transport for P-gp and BCRP cosubstrates. The BCRP levels in membrane extracts from MDCKII-BCRP or MDCKII-Bcrp1 cells were quantified by liquid chromatography-tandem mass spectrometry. The results are summarized as follows: 1) the membrane protein expression levels correlate with the corrected efflux ratios of substrates for human BCRP and murine BCRP1 within the efflux ratios investigated; 2) we demonstrate good concordance in rank order between the BCRP and BCRP1-mediated efflux ratios for 12 drugs; and 3) we propose an approach to contextualize in vitro BCRP transport data of discovery compounds by comparing them to the in vitro and in vivo transport data of the reference drug dantrolene and taking into account interbatch variation in BCRP expression. This approach correctly predicted compromised brain penetration for 25 discovery compounds in rodents, which were BCRP substrates but not P-gp or weak P-gp substrates. These results suggest that BCRP-expressing MDCKII cells are useful in predicting the in vivo role of BCRP in brain penetration.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Cell Membrane/metabolism , Neoplasm Proteins/metabolism , Pharmaceutical Preparations/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Animals , Biological Transport , Chromatography, Liquid , Dibenzocycloheptenes/pharmacology , Dogs , Madin Darby Canine Kidney Cells , Models, Biological , Neoplasm Proteins/genetics , Quinolines/pharmacology , Species Specificity , Substrate Specificity , Tandem Mass Spectrometry , Transfection
14.
Biomed Mater Eng ; 26 Suppl 1: S1855-62, 2015.
Article in English | MEDLINE | ID: mdl-26405957

ABSTRACT

To address the imbalanced classification problem emerging in Bioinformatics, a boundary movement-based extreme learning machine (ELM) algorithm called BM-ELM was proposed. BM-ELM tries to firstly explore the prior information about data distribution by condensing all training instances into the one-dimensional feature space corresponding to the original output in ELM, and then on the transformed space, to find the optimal moving distance of the classification hyperplane by estimating the probability density distributions of the instances in different classes. Experimental results on four real imbalanced bioinformatics classification data sets indicated that the proposed BM-ELM algorithm outperforms some traditional bias correction algorithms due to it can greatly improve the sensitivity of the classification results with small loss of specificity as possible. Also, BM-ELM algorithm has presented better performance than the widely used support vector machine (SVM) classifier. The algorithm can be widely popularized in various large-scale bioinformatics applications.


Subject(s)
Algorithms , High-Throughput Nucleotide Sequencing/methods , Pattern Recognition, Automated/methods , Sequence Alignment/methods , Sequence Analysis/methods , Support Vector Machine , Computer Simulation , Data Mining/methods , Databases, Genetic , Machine Learning , Models, Genetic , Models, Statistical
15.
Sci Rep ; 5: 11802, 2015 Jul 02.
Article in English | MEDLINE | ID: mdl-26136154

ABSTRACT

The present study aimed to explore the holistic mechanism for the antihypertrophic effect of a compound in Chinese medicine, QiShenYiQi Pills (QSYQ) and the contributions of its components to the effect in rats with cardiac hypertrophy (CH). After induction of CH by ascending aortic stenosis, rats were treated with QSYQ, each identified active ingredient (astragaloside IV, 3, 4-dihydroxy-phenyl lactic acid or notoginsenoside R1) from its 3 major herb components or dalbergia odorifera, either alone or combinations, for 1 month. QSYQ markedly attenuated CH, as evidenced by echocardiography, morphology and biochemistry. Proteomic analysis and western blot showed that the majority of differentially expressed proteins in the heart of QSYQ-treated rats were associated with energy metabolism or oxidative stress. Each ingredient alone or their combinations exhibited similar effects as QSYQ but to a lesser extent and differently with astragaloside IV and notoginsenoside R1 being more effective for enhancing energy metabolism, 3, 4-dihydroxy-phenyl lactic acid more effective for counteracting oxidative stress while dalbergia odorifera having little effect on the variables evaluated. In conclusion, QSYQ exerts a more potent antihypertrophic effect than any of its ingredients or their combinations, due to the interaction of its active components through a multi-component and multi-target mode.


Subject(s)
Cardiomegaly/drug therapy , Drugs, Chinese Herbal/administration & dosage , Heart/drug effects , Myocardium/metabolism , Animals , Cardiomegaly/physiopathology , Energy Metabolism/drug effects , Gene Expression Regulation/drug effects , Ginsenosides/administration & dosage , Heart/physiopathology , Oxidative Stress/drug effects , Pressure , Proteomics , Rats , Rats, Sprague-Dawley , Saponins/administration & dosage , Triterpenes/administration & dosage
16.
J Genet ; 91(2): 163-70, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22942086

ABSTRACT

Oryza sativa and Brassica napus-two important crops for food and oil, respectively-share high seed yield as a common breeding goal. As a model plant, O. sativa genomics have been intensively investigated and its agronomic traits have been advanced. In the present study, we used the available information on O. sativa to conduct comparative mapping between O. sativa and B. napus, with the aim of advancing research on seed-yield and yield-related traits in B. napus. Firstly, functional markers (from 55 differentially expressed genes between a hybrid and its parents) were used to detect B. napus genes that co-localized with yield-related traits in an F(2:3) population. Referring to publicly available sequences of 55 B. napus genes, 53 homologous O. sativa genes were subsequently detected by screening, and their chromosomal locations were determined using silico mapping. Comparative location of yield-related QTL between the two species showed that a total of 37 O. sativa and B. napus homologues were located in similar yield-related QTL between species. Our results indicate that homologous genes between O. sativa and B. napus may have consistent function and control similar traits, which may be helpful for agronomic gene characterization in B. napus based on what is known in O. sativa.


Subject(s)
Brassica napus/genetics , Genes, Plant , Genetic Linkage , Oryza/genetics , Quantitative Trait Loci , Brassica napus/anatomy & histology , Chromosome Mapping , Chromosomes, Plant , Genetic Markers , Oryza/anatomy & histology , Phenotype , Seeds/anatomy & histology , Seeds/genetics , Sequence Analysis, DNA , Sequence Homology, Nucleic Acid
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