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BACKGROUND@#Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.@*METHODS@#We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.@*RESULTS@#The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.@*CONCLUSION@#Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Arteries , Atrophy , Brain/metabolism , Cerebral Cortex/metabolism , Cerebrovascular Circulation , Constriction, Pathologic/pathology , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methodsABSTRACT
Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism, which is manifested by increased endogenous fat mobilization, hypertriglyceridemia, and increased fatty acid synthesis. Fatty acid synthase (FASN) is a key enzyme for the de novo synthesis of fatty acids, and monoacylglycerol esterase (MGLL) is an important metabolic enzyme that converts triglycerides into free fatty acids. Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways, the most common of which is the PI3K-AKT signaling pathway. They can also regulate the immune microenvironment, participate in epithelial-mesenchymal transition, and then regulate tumor invasion and metastasis. Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion. This article introduces the structures and functions of FASN and MGLL, their relationship with abnormal lipid metabolism, and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.
Subject(s)
Humans , Cell Line, Tumor , Fatty Acid Synthase, Type I/metabolism , Lipid Metabolism , Monoacylglycerol Lipases/metabolism , Neoplasms , Phosphatidylinositol 3-Kinases , Signal Transduction , Tumor MicroenvironmentABSTRACT
Objective To observe the fundus lesions in the unilateral rhegmatogenous retinal detachment (RRD) eyes and contralateral eyes in non-traumatic emmetropia patients,and explore the risks of lateral eyes.Methods This is a retrospective case analysis.A total of 426 patients of unilateral RRD diagnosed by clinical examination were enrolled in this study.There were 273 males and 74 females.The average age of onset was 54.7 years.81.46% of them (347 patients) were 51-70 years old.The average detachment time was 2.12 months.They were divided into two groups,equal or lesser than 50 years old group and more than 50 years old group.A total of 100 patients (200 eyes) with ocular surface disorders were randomly selected as control.The lattice-like degeneration,cystic degeneration and dry retinal holes were treated with prophylactic laser photocoagulation.Follow-up period was 6 to 24 months.The age,gender,proliferative vitreous retinopathy (PVR) grading,best corrected visual acuity (BCVA),distribution and quantity of retinal holes,and posterior vitreous detachment (PVD) were retrospectively analyzed.The incidence of PVD among different age groups was compared with Chi square.Results Among 426 RRD eyes,there were 239 eyes (56.10%) with PVD.Among them,there were 30 eyes with age equal or lesser than 50 years old (12.55%) and 209 eyes with age more than 50 years old (84.75%).There were 187 eyes (43.90%) without PVD,which including 38 eyes with age equal or lesser than 50 years old (20.32%) and 149 eyes with age more than 50 years old (79.68%).The incidence of PVD among different age groups was statistically significant (x2=4.72,P< 0.05).There were 10,254,40 and 5 eyes in class A,B,C and D of PVR,respectively;117 eyes without PVR.The retinal hole was located in superior temporal,inferior temporal,superior nasal,inferior nasal and macular in 305,91,22,4 and 4 eyes,respectively.The number of holes was 1,2,and more than 3 in 297,89 and 40 eyes,respectively.The retinal detachment range of 1,2,3 quadrants and total dissociation were 92,230,71,33 eyes,respectively.The fundus lesion was found in 47 eyes (11.03%) in the lateral eyes.There were 20 RRD eyes in class B of PVR,and 27 RRD eyes in class C of PVR.Retinal degenerated area was found.Among them,the degeneration of 41 eyes was located in the temporal retina,45 eyes involved in a quadrant.There were 16 eyes with peripheral retinal dry holes;the holes diameter was less than 1,1-2,greater than 2 optic-discs in 6,11 and 5 retinal holes.At the end of the follow-up,there were 47 eyes with almost normal visual field,16 eyes with decreased visual acuity,noeyes with retinal detachment.In the control group,4 patients (5 eyes,2.50%) had fundus lesions.Conclusion The unilateral RRD in non-traumatic emmetropia mostly occurs in elderly patients;11.03% of patients had fundus lesions in the contralateral eyes,higher than the general population.
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Objective To explore the ability of advanced oxidation protein products (AOPP)in predicting the progression of diabetic retinopathy (DR)in patients with type 2 diabetes mellitus (T2DM). Methods 363 T2DM patients were enrolled in this prospective cohort study. According to the quartile points of baseline AOPP level,patients were divided into four groups (Q1,Q2,Q3 and Q4 ). The progression rate of DR was calculated according to the changes of non-mydriatic fundus photography after a 5-year follow-up. Results With the increase of baseline AOPP level,the rate of progression of DR increased (19.51% vs 28.42% vs 37.36% vs 47.37%,P <0.01). Logistic regression analysis showed that baseline level of AOPP was an independent risk factor for the progression of DR (OR=1.833,95%CI:1.573~1.982,P<0.05).Area under the curve of AOPP in predicting DR is 0.883 (95% CI:0.842~0.924)with the sensitivity 86.1% and specificity 91.9%. Conclusion AOPP may be one of the biomarkers for the prediction of type 2 diabetic retinopathy progression.
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Objective To discuss the relationship between diabetic macular edema(DME) and visual field defects and evaluatethe therapeutic effect of micro-pulse laser.Methods A total of 117 patients (149 eyes) with diabetic retinopathy(DR) were enrolled in this study and divided into two groups according to early treatment diabetic retinopathy study(ETDRS) DME diagnostic criteria:DME group(n=50,70 eyes) and N-DME group(n=67,79 eyes).Healthy subjects(n=40,80 eyes)were selected as NC group in thisstudy.The clinical data and biochemical index were collectedand visual fields were examined in all the subjects.Then the DME group was further divided into two subgroups:micro-pulse laser subgroup(35 eyes) and conventional laser subgroup(35 eyes).The vision recovery after treatment was evaluated on different time points.Results Diabetes duration,FPG,HbA1c and HOMA-IR were significantly higher in DME group than in N-DME group (P0.05).Multiple logistic regression analysis showed that DM duration,FPG,HbA1c and HOMA-IR were riskfactors for DME(all P<0.01).Conclusion Patients with DME have severe vision loss.Micro-pulse laser therapy is helpful invision recovery,while conventional laser therapy have no obvious effect on it.Longer duration of DM,higher level of FPG,HbA1c,and IR severity may increase the risk of DME.