Search

In addition to membrane-integrated aquaporins, a novel secretory pore-forming protein, βγ-CAT, can facilitate toad water maintaining via macropinocytosis induction and exocytosis modulation, especially in responses to osmotic stress.

Summary: Nutrient acquisition is essential for animal cells. βγ-CAT is a pore-forming protein (PFP) and trefoil factor complex assembled under tight regulation identified in toad Bombina maxima. Here, we reported that B. maxima cells secreted βγ-CAT under glucose, glutamine, and pyruvate deficiency to scavenge extracellular proteins for their nutrient supply and survival. AMPK signaling positively regulated the expression and secretion of βγ-CAT. The PFP complex selectively bound extracellular proteins and promoted proteins uptake through endolysosomal pathways. Elevated intracellular amino acids, enhanced ATP production, and eventually prolonged cell survival were observed in the presence of βγ-CAT and extracellular proteins. Liposome assays indicated that high concentration of ATP negatively regulated the opening of βγ-CAT channels. Collectively, these results uncovered that βγ-CAT is an essential element in cell nutrient scavenging under cell nutrient deficiency by driving vesicular uptake of extracellular proteins, providing a new paradigm for PFPs in cell nutrient acquisition and metabolic flexibility.

DOI：10.3969/j.issn.1672-6731.2019.09.018

Objective To systematically review the correlation between genetic polymorphism of apolipoprotein E (ApoE) and late onset Alzheimer's disease (LOAD) in Chinese population. Methods Taking "ApoE, late onset Alzheimer's disease, polymorphism, China and Chinese" as retrieval words, databases of PubMed, EMBASE/SCOPUS, EBSCO-CINAHL, Cochrane Library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang Data were retrieved with computer for collecting case-control studies about the correlation between genetic polymorphism of ApoE and LOAD in Chinese population in recent 20 years. Newcastle-Ottawa Scale (NOS) was used for methodological quality assessment. Meta-analysis was conducted by using RevMan 5.0 software. Results There were a total of 249 records through preliminary searching. After eliminating 113 duplicate ones and 124 articles which did not meet the inclusion criteria and adding one article by searching the references of 27 screened articles, 13 high-quality clinical trials were finally selected (NOS score ≥ 5). A total of 3372 subjects (1360 LOAD patients and 2012 controls) were included. Meta-analysis showed that the LOAD risk in population with allele ApoEε4 was significantly higher than those with allele ApoEε3 (OR = 3.710, 95%CI:2.960-4.640; P = 0.000), while had no statistical difference from those with allele ApoEε 2. Meta-analysis also showed that the LOAD risk in those with genotype ApoEε3/ε4 (OR = 3.160, 95%CI: 2.390-4.180; P = 0.000), genotype ApoE ε 2/ε 4 (OR = 3.410, 95% CI: 2.160-5.380; P = 0.000), genotype ApoE ε 4/ε 4 (OR = 16.400, 95% CI: 8.200-32.810; P = 0.000) was significantly higher than those with genotype ApoE ε 3/ε 3, while had no statistical differences from those with genotype ApoE ε 2/ε 3 and genotype ApoE ε 2/ε 2. Conclusions The evidences indicate that ApoEε4 allele and ApoE genotype ε3/ε4, ε2/ε4 and ε4/ε4 are high risk factors for LOAD in Chinese population. DOI: 10.3969/j.issn.1672-6731.2016.01.006

Objective To explore the relationship between apolipoprotein E ε4 (ApoEε4) allele and blood lipid, and the relationship between ApoE ε 4 allele and the prognosis of acute ischemic stroke. Methods The study included 786 patients with acute ischemic stroke admitted in Tianjin Huanhu Hospital from December 1, 2013 to June 30, 2014. The ApoE genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), ApoA, ApoB levels were also measured. The relationship between ApoE ε 4 allele and blood lipid was analyzed. All patients were assessed by National Institute of Health Stroke Scale (NIHSS) on discharge, and they were divided into 2 groups according to NIHSS score: favorable prognosis group (NIHSS ≤ 10) and unfavorable prognosis group (NIHSS > 10). The relationship between ApoE ε 4 allele and the outcome was analyzed by univariate and forward multivariate Logistic regression analysis. Results The ApoEε 4 allele carriers had significantly higher LDL-C and ApoB levels than the non-ApoEε4 allele carriers [(3.25 ± 0.85) mmol/L vs (3.00 ± 0.83) mmol/L, P = 0.008; (1.20 ± 0.30) mmol/L vs (1.09 ± 0.25) mmol/L, P = 0.000]. Forward multivariate Logistic regression analysis showed NIHSS score on admission and modified Rankin Scale (mRS) on discharge were the major influencing factors for prognosis of acute ischemic stroke (P = 0.000, for all). The ApoE ε 4 had no significant outstanding influence on the outcome of acute ischemic stroke (P = 0.343). Conclusions The presence of ApoE ε 4 allele do not predict a worse outcome of acute ischemic stroke, but it is associated with increased LDL-C and ApoB in acute ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2015.02.007

A 58-year-old right handed woman, with 12 years of formal education, had a five-year history of slowly progressive blurred vision and apraxia. Five years before the examination she gradually became blurred vision and had difficulties identifying static objects within the visual field. Then she went to an ophthalmologist and received cataract surgery. However, the symptoms were not improved after surgery. Two years later, she had difficulty doing household chores and was unable to dress herself. She developed an anxiety disorder in the absence of prominent language or memory deficits. Five years after onset, she showed global cognitive decline and abilities of daily life decline. On neurological examination she was alert. Neuropsychological testing revealed a mini-mental state examination (MMSE) score of 20/30 with anomia, agraphia, alexia and partial impairment on time orientation. Biochemical investigations for disorders involving thyroid function, vitamin B12, and folate were unremarkable. A brain MRI showed diffuse cortical atrophy and hippocampus atrophy. An 18F-FDG PET scan showed bilateral hypometabolism at the frontal lobes, tempoparietooccipital adjunction, posterior cingulate cortices and precuneus, insular lobes, caudate nuclei and right thalamus. An 11C-PIB PET scan showed bilateral amyloid deposits at bilateral frontal lobes and occipital lobes, left temporal lobe and insular, basal ganglia, bilateral cingulate cortices and precuneus. No PSEN1, PSEN2 or APP mutations were identified. This early-onset patient had an unusual cognitive complaint, including visual agnosia and apraxia. The clinical features, structural and functional imaging findings of this case were compatible with the diagnosis of Posterior Cortical Atrophy (PCA). PCA is a neurodegenerative condition characterized by a progressive, often dramatic and relatively selective decline in visual processing skills and other functions subserved by parietal, occipital and occipito-temporal regions, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Often considered as an atypical or variant form of Alzheimer’s disease (AD), PCA typically presents in the mid-50s or early 60s with a variety of unusual symptoms, such as difficulty in interpreting, locating, or reaching for objects under visual guidance or difficulty in navigating. Understanding numbers and reading and writing or spelling may also be affected and, as the disease progresses, patients often develop a more diffuse pattern of cognitive dysfunction, ultimately leading to dementia. The vast majority (>80%) of PCA patients are found to have AD pathology as the cause of dementia at autopsy. Both PCA and AD patients show a similar pattern of high cortical binding on amyloid positron emission tomography (PET) imaging, and analogous changes in cerebrospinal fluid (CSF) level of Aβ42, total tau, and phosphorylated tau. PCA and AD show overlapping atrophy and hypometabolism/hypoperfusion in temporoparietal regions, suggesting a common anatomic focus of neurodegeneration. Structural neuroimaging with either MRI or CT initially shows greater atrophy of visual processing areas in parietotemporo-occipital cortex and relative sparing of critical memory regions in the medial temporal lobe. Over time, the neuroimaging profile of PCA may also merge with that of typical AD. This patient has five-year history of blurred vision and apraxia. At the time of examination, she has been in the stage of global cognitive declining. Diffuse cortical atrophy and hippocampus atrophy in MRI is very difficult to distinguish from typical AD. Hypometabolism and amyloid deposits from PET scan also showed overlapping with typical AD. doi: 10.3969/j.issn.1672-6731.2014.07.018

Background Catechol-O-methyltransferase (COMT) has a key function in the degradation of catecholamines and inactivating estrogen. A common polymorphism in the COMT gene is guanine-adenine (G-A) point mutation on rs4680, which causes a valine (Val) substitution to methionine (Met) in 108 and (or) 158 amino acid by this gene and is responsible for lowered activity of the enzyme. The Val/Met polymorphism has been recognized to be associated with psychiatric disorders, alcohol dependence and drug side effects, but few study has been done to examine the relationship with cerebral infarction (CI). The objective of this study is to investigate the relationship between the polymorphisms of COMT gene and CI. Methods The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect COMT Val158Met genotype in 181 CI patients and 148 cases of controls. Meanwhile the serum levels of glucose, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB) and ApoA in CI group were detected. Results The frequency of Val allele (78.45%) and Val/Val genotype (61.33%) in CI was significantly higher than that in the control group (68.24% and 45.95%, P < 0.05). Further analysis showed the frequency of Val allele in CI was significant higher in men (82.52% vs 66.67%, P < 0.01), but not in women (69.83% vs 69.07%, P > 0.05) than that in the control group. The serum levels of glucose, TC, TG, LDL-C, HDL-C, ApoB, ApoA and the frequency of hypertension had no difference between Val/Val genotype and Val/Met + Met/Met genotypes (P > 0.05, for all). Conclusion The frequencies of Val allele and Val/Val genotype can be considered as genetic risk factors of male CI patients. The effect of COMT on CI is not related to blood pressure, serum lipid and glucose.