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1.
Stroke ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38881452

ABSTRACT

BACKGROUND: Surgical risk assessment is intriguing for clinical decision-making of brainstem cavernous malformation (BSCM) treatment. While the BSCM grading scale, encompassing size, developmental venous anomaly, crossing axial midpoint, age, and timing of intervention, is increasingly utilized, the clinical relevance of neurological fluctuation and recurrent hemorrhage has not been incorporated. This study aimed to propose a supplementary grading scale with enhanced predictive efficacy. METHODS: Using a retrospective nationwide registry of consecutive patients with BSCMs undergoing surgery in China from March 2011 to May 2023, a new supplementary BSCM grading scale was developed from a derivative cohort of 260 patients and validated in an independent concurrent cohort of 67 patients. The primary outcome was unfavorable neurological function (modified Rankin Scale score >2) at the latest follow-up. The performance of the supplementary grading system was evaluated for discrimination, calibration, and clinical utility and further compared with its original counterpart. RESULTS: Over a follow-up of at least 6 months after surgery, the unfavorable outcomes were 31% in the overall cohort (101/327 patients). A preoperative motor deficit (odds ratio, 3.13; P=0.001), recurrent hemorrhage (odds ratio, 3.05; P<0.001), timing of intervention (odds ratio, 7.08; P<0.001), and crossing the axial midpoint (odds ratio, 2.57; P=0.006) were associated with the unfavorable outcomes and composed the initial Huashan grading variables. A supplementary BSCM grading system was subsequently developed by incorporating the Huashan grading variables into the original BSCM grading scale. The predictive capability of the supplementary scale was consistently superior to the original counterpart in either the derivative cohort (area under the receiver operating characteristic curve, 0.74 [95% CI, 0.68-0.80] for the supplementary versus 0.68 [95% CI, 0.61-0.74] for the original) or the validation cohort (0.75 [95% CI, 0.62-0.87] versus 0.64 [95% CI, 0.48-0.81]). CONCLUSIONS: This study highlights the neurological relevance of BSCM hemorrhage in surgical risk assessment. Via compositing preoperative motor function and recurrent hemorrhages, a supplementary grading scale may improve a dynamic risk assessment for clinical decisions in the management of BSCMs.

2.
Cancer Sci ; 115(1): 83-93, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37985391

ABSTRACT

Autoantibodies (AAbs) in the blood of colorectal cancer (CRC) patients have been evaluated for tumor detection. However, it remains uncertain whether these AAbs are specific to tumor-associated antigens. In this study, we explored the IgG and IgM autoantibody repertoires in both the in situ tissue microenvironment and peripheral blood as potential tumor-specific biomarkers. We applied high-density protein arrays to profile AAbs in the tumor-infiltrating lymphocyte supernatants and corresponding serum from four patients with CRC, as well as in the serum of three noncancer controls. Our findings revealed that there were more reactive IgM AAbs than IgG in both the cell supernatant and corresponding serum, with a difference of approximately 3-5 times. Immunoglobulin G was predominant in the serum, while IgM was more abundant in the cell supernatant. We identified a range of AAbs present in both the supernatant and the corresponding serum, numbering between 432 and 780, with an average of 53.3% shared. Only 4.7% (n = 23) and 0.2% (n = 2) of reactive antigens for IgG and IgM AAbs, respectively, were specific to CRC. Ultimately, we compiled a list of 19 IgG AAb targets as potential tumor-specific AAb candidates. Autoantibodies against one of the top candidates, p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A (RPRD1A), were significantly elevated in 53 CRC patients compared to 119 controls (p < 0.0001). The project revealed that tissue-derived IgG AAbs, rather than IgM, are the primary source of tumor-specific AAbs in peripheral blood. It also identified potential tumor-specific AAbs that could be applied for noninvasive screening of CRC.


Subject(s)
Autoantibodies , Colorectal Neoplasms , Humans , Biomarkers, Tumor , Immunoglobulin G , Immunoglobulin M , Tumor Microenvironment , Repressor Proteins , Cell Cycle Proteins
3.
Eur Radiol ; 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37857901

ABSTRACT

OBJECTIVE: To investigate the association between chronic headache outcome and aneurysmal wall enhancement (AWE) on high-resolution vessel wall imaging (HR-VWI) in patients with unruptured intracranial aneurysms (UIAs) who underwent microsurgical clipping. METHODS: Two hundred seventy-four UIA patients were retrospectively analyzed. Patients were grouped according to presence of AWE. AWE was subclassified as focal or uniform. Clinical and imaging data were recorded. Headache was evaluated using the 10-point numerical rating scale and Headache Impact Test-6 before and 6 months after surgery. RESULTS: The proportions of patients reporting chronic headache in the no AWE, focal wall enhancement (FWE), and uniform wall enhancement (UWE) groups were 5.7%, 24.8%, and 41.8%, respectively. All patients in the UWE group who reported headache before surgery experienced headache improvement after surgery. Decrease in headache severity was greater in the UWE group than in the FWE group. Multivariate binary logistic regression showed that FWE (odds ratio (OR) 0.490; 95% confidence interval (CI), 0.262-0.917; p = 0.026) and small intraluminal thrombus (OR 0.336; 95% CI, 0.142-0.795; p = 0.013) were independent factors protective against preoperative headache. FWE (OR 0.377; 95% CI, 0.195-0.728; p = 0.004) and small intraluminal thrombus (OR 0.235; 95% CI, 0.088-0.630; p = 0.004) were independent predictors of no headache relief after surgery. CONCLUSIONS: AWE on HR-VWI is associated with relief of chronic headache after surgical clipping in patients with UIAs. Incidence of chronic headache was highest in patients exhibiting UWE. These patients also experienced the greatest improvement in headache after surgical clipping. CLINICAL RELEVANCE STATEMENT: This study revealed that high-resolution vessel wall imaging can demonstrate aneurysmal wall plaque and intraluminal thrombus, which may be prognostic imaging markers for chronic headache in patients with unruptured intracranial aneurysms. KEY POINTS: • Aneurysmal wall enhancement may be associated with chronic headache. • Incidence of chronic headache was highest in patients with aneurysms exhibiting uniform wall enhancement. • Patients with aneurysms exhibiting uniform wall enhancement experienced the greatest improvement in headache after clipping.

4.
Neurosurg Rev ; 46(1): 153, 2023 Jun 26.
Article in English | MEDLINE | ID: mdl-37365456

ABSTRACT

Arteriovenous fistulas (AVFs) at the craniocervical junction (CCJ) are uncommon conditions with complex angioarchitecture. The objective of this study was to identify the angioarchitectural features of CCJ-AVF that were predictive of clinical presentation and neurological function. The study encompassed a total of 68 consecutive patients with CCJ-AVF at two neurosurgical centers between 2014 and 2022. Additionally, a systematic review was conducted, including 68 cases with detailed clinical data obtained via PubMed database spanning 1990 to 2022. Clinical and imaging data were collected and pooled together to analyze factors associated with subarachnoid hemorrhage (SAH), myelopathy, and modified Rankin scale (mRS) at presentation. The mean age of the patients was 54.5 ± 13.1 years, with 76.5% of them being male. The most common feeding arteries were V3-medial branches (33.1%), and drainage was frequently through the anterior or posterior spinal vein/perimedullary vein (72.8%). SAH was the most common presentation (49.3%), and an associated aneurysm was identified as a risk factor for SAH (adjusted OR, 7.44; 95%CI, 2.89-19.15). Anterior or posterior spinal vein/perimedullary vein (adjusted OR, 2.78; 95%CI, 1.00-7.72) and male gender (adjusted OR, 3.76; 95%CI, 1.23-11.53) were associated with higher risk for myelopathy. Myelopathy at presentation was an independent risk factor for unfavorable neurological status (adjusted OR per score, 4.73; 95%CI, 1.31-17.12) in untreated CCJ-AVF. The present study identifies risk factors associated with SAH, myelopathy, and unfavorable neurological status at presentation in patients with CCJ-AVF. These findings may help treatment decisions for these complex vascular malformations.


Subject(s)
Arteriovenous Fistula , Central Nervous System Vascular Malformations , Spinal Cord Diseases , Subarachnoid Hemorrhage , Humans , Male , Adult , Middle Aged , Aged , Female , Subarachnoid Hemorrhage/complications , Arteriovenous Fistula/complications , Arteriovenous Fistula/surgery , Spinal Cord Diseases/surgery , Central Nervous System Vascular Malformations/surgery , Central Nervous System Vascular Malformations/complications , Multicenter Studies as Topic
5.
Anim Biotechnol ; 34(7): 3126-3134, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36306180

ABSTRACT

Adipose triglyceride lipase (ATGL) is the key enzyme for the degradation of triacylglycerols (TAGs). It functions in concert with other enzymes to mobilize TAG and supply fatty acids (FAs) for energy production. Dysregulated lipolysis leads to excess concentrations of circulating FAs, which may lead to destructive and lipotoxic effects to the organism. To understand the role of ATGL in mammary lipid metabolism, ATGL was overexpressed in goat mammary epithelial cells (GMECs) by using a recombinant adenovirus system. ATGL overexpression decreased lipid droplet (LD) accumulation and cellular TG content (p < 0.05) along with a decrease in the expression of the key enzyme that catalyzes the final step of TG synthesis (DGAT). Significant increases were observed in the expression of genes related to lipolysis (hormone-sensitive lipase [HSL]) and FA desaturation (SCD) by ATGL overexpression. Genes responsible for FA oxidation (PPARα), LD formation and secretion (ADRP and BTN1A1), and long-chain FA uptake (CD36) were all decreased by ATGL overexpression (p < 0.05). The primary products of TAG lipolysis, free FAs (FFAs), were notably increased in the ATGL-overexpressing cells. Taken together, our results demonstrated that ATGL activation impairs lipid formation partially through accelerating lipolysis in GMECs.


Subject(s)
Lipase , Lipolysis , Animals , Lipolysis/physiology , Lipase/genetics , Lipase/metabolism , Lipid Droplets/metabolism , Goats/metabolism , Fatty Acids , Epithelial Cells/metabolism
6.
Anim Biotechnol ; 34(9): 4580-4587, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36794322

ABSTRACT

This study aimed to identify the target genes of IGFBP3(insulin growth factor binding protein)protein and to investigate its target genes effects on the proliferation and differentiation of Hu sheep skeletal muscle cells. IGFBP3 was an RNA-binding protein that regulates mRNA stability. Previous studies have reported that IGFBP3 promotes the proliferation of Hu sheep skeletal muscle cells and inhibits differentiation, but the downstream genes that bind to it have not been reported yet. We predicted the target genes of IGFBP3 through RNAct and sequencing data, and verified by qPCR and RIP(RNA Immunoprecipitation)experiments, and demonstrated GNAI2(G protein subunit alpha i2)as one of the target gene of IGFBP3. After interference with siRNA, we carried out qPCR, CCK8, EdU, and immunofluorescence experiments, and found that GNAI2 can promote the proliferation and inhibit differentiation of Hu sheep skeletal muscle cells. This study revealed the effects of GNAI2 and provided one of the regulatory mechanisms of IGFBP3 protein underlying sheep muscle development.


Subject(s)
Insulin-Like Growth Factor Binding Protein 3 , Muscle Fibers, Skeletal , Animals , Sheep/genetics , Insulin-Like Growth Factor Binding Protein 3/genetics , Insulin-Like Growth Factor Binding Protein 3/metabolism , Muscle Fibers, Skeletal/metabolism , RNA, Small Interfering , Cell Differentiation , Cell Proliferation/genetics , Muscle, Skeletal/metabolism
7.
Acta Neurochir (Wien) ; 165(12): 3787-3791, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37845355

ABSTRACT

BACKGROUND: This report described the surgical resection of a challenging medial parietal lobe arteriovenous malformation (AVM) using the hybrid operation theater with a multimodal imaging-guided technology. METHOD: A 29-year-old male was admitted to treat a ruptured medial parietal AVM. The deep and diffusive compartment of the nidus was embolized before resection. Preoperatively and intraoperatively, mixed reality technology with multimodality imaging was utilized for surgical planning and navigation. The nidus was totally resected and confirmed by intraoperative angiography. The patient recovered without sequella. CONCLUSION: We hope this report provides new insights into applying multimodal imaging technology-guided hybrid operation for brain AVM.


Subject(s)
Intracranial Arteriovenous Malformations , Male , Humans , Adult , Intracranial Arteriovenous Malformations/diagnostic imaging , Intracranial Arteriovenous Malformations/surgery , Neurosurgical Procedures/methods , Parietal Lobe/diagnostic imaging , Parietal Lobe/surgery , Cerebral Angiography/methods , Multimodal Imaging
8.
Anim Biotechnol ; : 1-9, 2022 Nov 17.
Article in English | MEDLINE | ID: mdl-36384387

ABSTRACT

Previous studies have shown that melatonin has a certain regulatory effect on the growth of sheep wool. However, the mechanism of melatonin action remains unknown. In the present study, we aimed to understand the role of exogenous melatonin in the dermal papilla cells of Hu sheep. To confirm the optimal melatonin treatment regimen for Hu sheep dermal papilla cells, we detected the cell viability by exposing them to different concentrations of melatonin and different treatment times. The results showed that cell viability was best when dermal papilla cells were treated with 1000 pg/ml of melatonin for 48 h. According to the results of qPCR, CCK-8, EDU, Western blot, and Flow cytometry analysis, we found that 1000 pg/ml melatonin promoted the proliferation and inhibited the apoptosis of dermal papilla cells compared with the exogenous melatonin blank group (control group). Furthermore, we also found that 1000 pg/ml of melatonin promoted the cell cycle progress of dermal papilla cells according to the results of qPCR and Flow cytometry analysis. Overall, our findings showed that melatonin plays an important role in the dermal papilla cells of Hu sheep.

9.
Genomics ; 113(1 Pt 2): 484-492, 2021 01.
Article in English | MEDLINE | ID: mdl-32976974

ABSTRACT

N6-methyladenosine (m6A) mRNA methylation varies in response to stress. However, no map of m6A mRNA methylation has been obtained for sheep, nor is it known what effect this has on regulating heat stress in sheep. Here, we obtained m6A methylation maps of sheep liver tissues with and without heat stress by MeRIP-seq. In total, 8306 m6A peaks associated with 2697 genes were detected in the heat stress group, and 12,958 m6A peaks associated with 5494 genes were detected in the control group. Peaks were mainly enriched in coding regions and near stop codons with classical RRACH motifs. Methylation levels of heat stress and control sheep were higher near stop codons, although methylation was significantly lower in heat stress sheep. GO and KEGG revealed that differential m6A-containing genes were significantly enriched in the stress response and fat metabolism. Our results showed that m6A mRNA methylation modifications regulate heat stress in sheep.


Subject(s)
Adenosine/analogs & derivatives , Heat-Shock Response , Liver/metabolism , RNA Processing, Post-Transcriptional , Adenosine/metabolism , Animals , Methylation , RNA, Messenger/metabolism , Sheep
10.
J Nanobiotechnology ; 19(1): 123, 2021 Apr 29.
Article in English | MEDLINE | ID: mdl-33926468

ABSTRACT

BACKGROUND: An endovascular covered-stent has unique advantages in treating complex intracranial aneurysms; however, in-stent stenosis and late thrombosis have become the main factors affecting the efficacy of covered-stent treatment. Smooth-muscle-cell phenotypic modulation plays an important role in late in-stent stenosis and thrombosis. Here, we determined the efficacy of using covered stents loaded with drugs to inhibit smooth-muscle-cell phenotypic modulation and potentially lower the incidence of long-term complications. METHODS: Nanofiber-covered stents were prepared using coaxial electrospinning, with the core solution prepared with 15% heparin and 20 µM rosuvastatin solution (400: 100 µL), and the shell solution prepared with 120 mg/mL hexafluoroisopropanol. We established a rabbit carotid-artery aneurysm model, which was treated with covered stents. Angiography and histology were performed to evaluate the therapeutic efficacy and incidence rate of in-stent stenosis and thrombosis. Phenotype, function, and inflammatory factors of smooth-muscle cells were studied to explore the mechanism of rosuvastatin action in smooth-muscle cells. RESULT: Heparin-rosuvastatin-loaded nanofiber scaffold mats inhibited the proliferation of synthetic smooth-muscle cells, and the nanofiber-covered stent effectively treated aneurysms in the absence of notable in-stent stenosis. Additionally, in vitro experiments showed that rosuvastatin inhibited the smooth-muscle-cell phenotypic modulation of platelet-derived growth factor-BB induction and decreased synthetic smooth-muscle-cell viability, as well as secretion of inflammatory cytokines. CONCLUSION: Rosuvastatin inhibited the abnormal proliferation of synthetic smooth-muscle cells, and heparin-rosuvastatin-loaded covered stents reduced the incidence of stenosis and late thrombosis, thereby improving the healing rates of stents used for aneurysm treatment.


Subject(s)
Cell Survival/drug effects , Constriction, Pathologic/drug therapy , Heparin/pharmacology , Muscles/drug effects , Nanofibers/chemistry , Polyesters/chemistry , Rosuvastatin Calcium/pharmacology , Thrombosis/drug therapy , Animals , Apoptosis/drug effects , Cell Proliferation/drug effects , Cytokines/metabolism , Intracranial Aneurysm/therapy , Male , Mice , Polyesters/pharmacology , Rabbits , Stents , Thrombosis/pathology
11.
J Sep Sci ; 44(3): 759-766, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33253473

ABSTRACT

An efficient method of recovering and recycling solvent for counter-current chromatography was established by which zeaxanthin was separated from Lycium barbarum L. fruits. A column with activated carbon combined with high performance counter-current chromatography formed the recovering and recycling solvent system. Using the solvent system of n-hexane-ethyl acetate-ethanol-water (8:2:7:3, v/v) from the references, five injections were performed with an almost unchanged purity of zeaxanthin (80.9, 81.2, 81.5, 81.3, and 80.2% respectively) in counter-current chromatography separation. Meanwhile, the mobile phase reduced by half than conventional counter-current chromatography. By this present method, an effective improvement of counter-current chromatography solvent utilization was achieved.


Subject(s)
Fruit/chemistry , Lycium/chemistry , Plant Extracts/isolation & purification , Zeaxanthins/isolation & purification , Chromatography, High Pressure Liquid , Countercurrent Distribution , Plant Extracts/chemistry , Solvents/chemistry , Zeaxanthins/chemistry
12.
Reprod Domest Anim ; 56(1): 12-25, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33073450

ABSTRACT

Intersexuality is a congenital reproductive disorder that usually occurs in hornless goats, hindering breeding of goats with hornless traits and the development of the goat industry. In this study, we aimed to identify differentially expressed genes in intersex and normal goat gonads by comparing gene transcription profiles of intersex and normal goat gonads. As intersex goats are genetically based on females, we chose female goats as controls. The goats in the control group and the experimental group were both over one-year old. We evaluated the anatomical characteristics of the reproductive organs of five intersex goats using histopathological methods. The gonads were found to be ovarian and testicular types. RNA-Seq technology was used to identify differentially expressed genes in gonads and normal goat ovary tissues. Transcription analysis results were verified by qPCR. The results showed that 2,748 DEGs were upregulated and 3,327 DEGs were downregulated in intersex ovaries unlike in controls, whereas 2006 DEGs were upregulated and 2032 DEGs were downregulated in the interstitial testes. Many of these genes play important roles in mammalian sex determination and sex differentiation, such as SOX9, WT1, GATA4, DMRT1, DHH, AMH, CYP19A1 and FST. We found that many DEGs are involved in biological developmental regulation by GO and KEGG enrichment analyses, and that most genes associated with the steroid synthesis pathway were downregulated. The DEGs identified in this study may be involved in the regulation of intersex goat sex determination and differentiation, and may increase our understanding of the molecular mechanisms of mammalian sex differentiation.


Subject(s)
Disorders of Sex Development/veterinary , Goat Diseases/genetics , Gonads/anatomy & histology , Animals , Disorders of Sex Development/genetics , Female , Gene Expression Profiling/veterinary , Gene Expression Regulation, Developmental , Goats , Gonads/metabolism , Ovary/metabolism , Sex Determination Processes
13.
J Neuroinflammation ; 17(1): 191, 2020 Jun 16.
Article in English | MEDLINE | ID: mdl-32546267

ABSTRACT

BACKGROUND: The regulation of vascular smooth muscle cell (VSMC) phenotype plays an important role in intracranial aneurysm (IA) formation and progression. However, the underlying mechanism remains unclear. Metformin is a 5' AMP-activated protein kinase (AMPK) agonist that has a protective effect on vasculature. The present study investigated whether metformin modulates VSMC phenotype switching via the AMPK/acetyl-CoA carboxylase (ACC) pathway during IA pathogenesis. METHODS: Adult male Sprague-Dawley rats (n = 80) were used to establish an elastase-induced IA model. The effects of metformin on AMPK activation and VSMC phenotype modulation were examined. We also established a platelet-derived growth factor (PDGF)-BB-induced VSMC model and analyzed changes in phenotype including proliferation, migration, and apoptosis as well as AMPK/ACC axis activation under different doses of metformin, AMPK antagonist, ACC antagonist, and their combinations. RESULTS: Metformin decreased the incidence and rupture rate of IA in the rat model and induced a switch in VSMC phenotype from contractile to synthetic through activation of the AMPK/ACC pathway, as evidenced by upregulation of VSMC-specific genes and decreased levels of pro-inflammatory cytokines. AMPK/ACC axis activation inhibited the proliferation, migration, and apoptosis of VSMCs, in which phenotypic switching was induced by PDGF-BB. CONCLUSIONS: Metformin protects against IA formation and rupture by inhibiting VSMC phenotype switching and proliferation, migration, and apoptosis. Thus, metformin has therapeutic potential for the prevention of IA.


Subject(s)
Intracranial Aneurysm/pathology , Metformin/pharmacology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/metabolism , Animals , Disease Progression , Intracranial Aneurysm/metabolism , Male , Phenotype , Rats , Rats, Sprague-Dawley
14.
Trop Anim Health Prod ; 53(1): 35, 2020 Nov 23.
Article in English | MEDLINE | ID: mdl-33230646

ABSTRACT

Huang-huai sheep are a new multiparous mutton sheep breed that has been cultivated by domestic scientific research institutes, governments, and sheep farms in China. Huang-huai sheep were bred using Dorper sheep as a sire and Small-tailed Han sheep as a dam. The breeding of Huang-huai sheep started in 2003, and three stages have been carried out: crossbreeding innovation, fixation in a two-way-crossbred closed flock, and herd propagation. A pilot test of Huang-huai sheep was conducted on 6 sheep farms from 2017 to 2018, and hereditary properties and production performance were evaluated in 2019. Huang-huai sheep were identified on site by the National Livestock and Poultry Resources Committee of China in December 2019 and approved as a new multiparous mutton sheep breed in China. The genetic distance showed that Huang-huai sheep are most closely related to Dorper sheep, Luxi black-headed sheep, and Small-tailed Han sheep, but the genetic distances are subspecies (0.02-0.20) each other. The body weights of adult Huang-huai sheep are 98.1 ± 5.2 kg (♂) and 71.7 ± 3.5 kg (♀), and those of 6-month-old Huang-huai sheep are 58.50 ± 6.55 kg (♂) and 52.45 ± 5.67 kg (♀). The slaughter rates of 6-month-old sheep are 56.02 ± 1.25% (♂) and 53.19 ± 1.19% (♀). The estrus cycle of Huang-huai sheep is 19.32 ± 2.8 days, the first estrus cycle occurs at 168 ± 12 days, the annual lambing rate of ewes is 252.82% ± 10.69%, the survival rate of lambs is 95.79 ± 0.95%, and the number of weaned lambs per ewe per year is 2.38 ± 0.14. The growth performance, carcass quality, and reproductive performance of Huang-huai sheep have been improved, resulting in considerable economic and social benefits and broader market prospects. This breed represents a new multiparous mutton sheep breed adapted for industrial sheep farms in China.


Subject(s)
Sheep/classification , Sheep/genetics , Animals , Body Weight/genetics , China , Female , Male , Pregnancy , Reproduction/genetics , Sheep/physiology
15.
Stroke ; 50(6): 1570-1573, 2019 06.
Article in English | MEDLINE | ID: mdl-31035900

ABSTRACT

Background and Purpose- High-resolution vessel wall magnetic resonance imaging is a promising technique for assessing wall structures of unruptured intracranial aneurysms (UIAs). However, the relationship between aneurysmal high-resolution vessel wall magnetic resonance imaging features and their histopathologic mechanism remains poorly understood. Methods- From February 2016 to February 2018, a total of 19 men and 28 women with 54 UIAs treated surgically were prospectively enrolled. The intraoperative observed gross pathology of the aneurysmal wall was compared with the enhancement features on high-resolution vessel wall magnetic resonance imaging. Specimens of the UIAs were harvested for histopathologic and immunohistochemistry analysis. Results- An irregular shape and large size was significantly related to UIA wall enhancement. Both uniform and focal wall enhancement may demonstrate the inflammation processes of UIA walls, although the latter may indicate more atherosclerotic plaque formation. Conclusions- Different high-resolution vessel wall magnetic resonance imaging enhancement features may represent variable inflammation status of a UIA wall, which may provide new insights into assessing the UIA wall structure and optimizing treatment.


Subject(s)
Intracranial Aneurysm , Magnetic Resonance Angiography , Plaque, Atherosclerotic , Adult , Aged , Biomarkers , Female , Humans , Inflammation/diagnostic imaging , Inflammation/surgery , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Male , Middle Aged , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/surgery
16.
Lab Invest ; 99(4): 588-598, 2019 04.
Article in English | MEDLINE | ID: mdl-30573870

ABSTRACT

The metabolic genes encoding isocitrate dehydrogenase (IDH1, 2) are frequently mutated in gliomas. Mutation of IDH defines a distinct subtype of glioma and predicts therapeutic response. IDH mutation has a remarkable neomorphic activity of converting α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG), which is now commonly referred to as an oncometabolite and biomarker for gliomas. PCR-sequencing (n = 220), immunohistochemistry staining (IHC, n = 220), and gas chromatography mass spectrometry (GC-MS, n = 87) were applied to identify IDH mutation in gliomas, and the sensitivity and specificity of these strategies were compared. PCR-sequencing and IHC staining are reliable for retrospective assessment of IDH1 mutation in gliomas, but both methods usually take 1-2 days, which hinders their application for rapid diagnosis. GC-MS-based methods can detect 2-HG qualitatively and quantitatively, offering information on the IDH1 mutation status in gliomas with the sensitivity and specificity being 100%. Further optimization of the GC-MS based methodology (so called as the mini-column method) enabled us to determine 2-HG within 40 min in glioma samples without complex or time-consuming preparation. Most importantly, the ratio of 2-HG/glutamic acid was shown to be a reliable parameter for determination of mutation status. The mini-column method enables rapid identification of 2-HG, providing a promising strategy for intraoperative diagnosis of IDH1-mutated gliomas in the future.


Subject(s)
Brain Neoplasms , Gas Chromatography-Mass Spectrometry/methods , Glioma , Glutarates/analysis , Isocitrate Dehydrogenase/genetics , Adult , Brain Neoplasms/chemistry , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Glioma/chemistry , Glioma/diagnosis , Glioma/genetics , Humans , Immunohistochemistry , Middle Aged , Mutation/genetics
17.
J Neuroinflammation ; 16(1): 185, 2019 Oct 04.
Article in English | MEDLINE | ID: mdl-31585542

ABSTRACT

BACKGROUND: Oxidative stress and vascular smooth muscle cell (VSMC) phenotypic modulation influence intracranial aneurysm (IA) formation and progression. Oxidative stress plays an important role in phenotype switching, and nuclear factor erythroid 2-related factor 2 (Nrf-2) is one of the main antioxidant systems. Unfortunately, little is known about how Nrf-2 signaling influences VSMC phenotype switches during IA pathogenesis. METHODS: We examined the effect of Nrf-2 activation IA on formation and progression in an elastase-induced rat IA model. We also developed a hydrogen peroxide (H2O2)-induced VSMC oxidative damage model. Then, we analyzed VSMC phenotype changes in the setting of Nrf-2 activation or inhibition in vitro. The proliferation, migration ability, and apoptosis rate of VSMCs were tested. Lastly, we measured the expression levels of antioxidant enzymes and inflammatory cytokines downstream of Nrf-2. RESULTS: Nrf-2 activation suppressed IA formation and progression in vivo. We confirmed Nrf-2 nuclear translocation and a VSMC switch from the contractile to synthetic phenotype. Nrf-2 activation inhibited the proliferation, migratory ability, and apoptosis rate enhanced by H2O2. Quantitative real-time polymerase chain reaction (PCR) and western blot analysis revealed that Nrf-2 activation promoted antioxidant enzymes and VSMC-specific marker gene expressions but decreased pro-inflammatory cytokine levels. CONCLUSION: These results suggest that Nrf-2 exerts protective effects against IA development by preventing VSMCs from changing to a synthetic phenotype.


Subject(s)
Intracranial Aneurysm/metabolism , Intracranial Aneurysm/pathology , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , NF-E2-Related Factor 2/metabolism , Animals , Disease Progression , Male , Phenotype , Rats , Rats, Sprague-Dawley , Signal Transduction/physiology
18.
J Sep Sci ; 42(2): 547-555, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30427121

ABSTRACT

In this work, to further verify and develop the novel counter-current chromatography modified column separate mode, a melamine modified counter-current chromatography column was prepared. Meanwhile, the modified counter-current chromatography column was used to separate stevioside and rebaudioside A with the same partition coefficient in chosen solvent system to evaluate its separation efficiency. The results show that because of the presence of intermolecular forces between melamine and model compounds, better separation could be achieved on the modified column while it's almost impossible to be separated on the unmodified column. So the results of this research further show that column modified method is a possible approach to further increase the separation ability of counter-current chromatography. Take advantage of large sample handing capacity of counter-current chromatography, the mothed may have great potential to be an efficient method of separation and preparation enantiomer compounds.

19.
Cell Physiol Biochem ; 45(3): 1051-1060, 2018.
Article in English | MEDLINE | ID: mdl-29439246

ABSTRACT

BACKGROUND/AIMS: Cerebral aneurysm growth is characterized by continuous structural weakness of local smooth muscle cells, though the mechanism is unclear. In this study, we examine protein changes in cerebral aneurysm and human brain vascular smooth muscle cells after cyclic mechanical stretch. We further explore the relationship between the smooth muscle cell changes and reductions in the levels of collagen types IV and VI. METHODS: Saccular cerebral aneurysms (n=10) were collected, and temporal artery samples were used as controls. Quantitative proteomics were analyzed and histopathological changes were examined. Smooth muscle cells were cultured in a flexible silicone chamber and subjected to 15% cyclic mechanical stretch. The effect of stretch on the cell viability, function, gene and protein expression were further studied for the understanding the molecular mechanism of aneurysm development. RESULTS: Proteomics analysis revealed 92 proteins with increased expression and 88 proteins with decreased expression compared to the controls (p<0.05). KEGG pathway analysis showed that the change in focal adhesion and extracellular matrix-receptor interaction, suggesting the involvement of collagen type IV and VI. The aneurysm tissue exhibited fewer smooth muscle cells and lower levels of collagen type IV and VI. Human brain vascular smooth muscle cell culture showed spindle-like cells and obvious smooth muscle cell layer. Cell proteomics analysis showed that decreased expression of 118 proteins and increased expression of 32 proteins in smooth muscle cells after cyclic mechanical stretch. KEGG pathway analysis indicated that focal adhesion and ECM-receptor interaction were involved. After cyclic mechanical stretch, collagen type IV and IV expression were decreased. Moreover, the stretch induced MMP-1 and MMP-3 expression elevation. CONCLUSION: We demonstrated that collagen type IV and VI were decreased in cerebral aneurysms and continuous cyclic mechanical stretch induced smooth muscle cell changes. Smooth muscle cell protection provides an additional therapeutic option to prevent the growth of cerebral aneurysms.


Subject(s)
Collagen Type IV/metabolism , Collagen Type VI/metabolism , Intracranial Aneurysm/pathology , Stress, Mechanical , Actins/metabolism , Cells, Cultured , Chromatography, High Pressure Liquid , Down-Regulation , Humans , Intracranial Aneurysm/metabolism , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 3/metabolism , Myocytes, Smooth Muscle , Peptides/analysis , Proteomics , Tandem Mass Spectrometry , Up-Regulation
20.
Chirality ; 2018 Jun 04.
Article in English | MEDLINE | ID: mdl-29864196

ABSTRACT

In chiral separation, enantioseparation factor is an important parameter which influences the resolution of enantiomers. In this current overview, a biphasic chiral recognition method is introduced to the readers. This method can significantly improve the enantioseparation factor in two-phase solvent through adding lipophilic and hydrophilic chiral selectors which have opposite chiral recognition ability to organic and aqueous phases, respectively. This overview presents the development and applications of biphasic chiral recognition in liquid-liquid extraction and counter current chromatography. It mainly focuses on the topics of mechanism, advantages and limitations, applications, and key factors of biphasic chiral recognition. In addition, the future outlook on development of biphasic chiral recognition also has been discussed in this overview.

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