Beibei Liu

University of California, San Diego

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Hua Yang

Chinese Institute for Brain Research

Zhongying Zhang

Kobe University

Lingyun Jia

Chinese Institute for Brain Research

Xianghua Fang

Guangdong Provincial Hospital of Traditional Chinese Medicine

Liqun Jiao

Capital Medical University

Chunxiu Wang

Capital Medical University

Xiang Gu

Chinese Academy of Medical Sciences & Peking Union Medical College

Yumei Liu

Harbin Medical University

Shaochen Guan

Capital Medical University

Zhe Tang

Capital Medical University

Cooperative Institutions

Capital Medical University

Peking University

Chinese Academy of Medical Sciences & Peking Union Medical College

Universität Hamburg

Chinese Academy of Sciences

University Medical Center Hamburg-Eppendorf

Huazhong University of Science and Technology

Shanghai Jiao Tong University

Peking University Third Hospital

Zhengzhou University

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Abstract WP134: Decreased Flow Velocities After General Anesthesia Before Carotid Endarterctomy Are Not Associated with Cerebral Hyperperfusion Syndrome or Perioperative Cerebral Infarction

Stroke (2017)

Yumei Liu Hua Yang Liqun Jiao Beibei Liu Jingzhi Li

Introduction: Cerebral Hyperperfusion Syndrome (CHS) is a life threatening complication in about 3% of patients following carotid endarterectomy (CEA). There is a concern that baseline flow velocities typically decrease after general anesthesia (GA) may predispose patients to CHS and other perioperative adverse events. Hypothesis: Patients with decreased flow velocity after GA are at increased risk for CHS using ultrasonographic and clinical diagnostic criteria. Methods: We retrospectively evaluated 920 patients who received CEA from 2006 to 2016 at a major hospital in China. Middle cerebral artery blood flow velocities were measured when patients were awake and after induction of the GA. Ultrasonographic diagnostic criterion of CHS was “100% increase in flow velocity by TCD from the baseline to post-CEA”. Patients were classified into two groups: NORMAL group if flow velocity decreased <30% and LOW group if decreased >=30%. The occurrences of CHS by ultrasonongraphic and clinical criteria, perioperative cerebral infarction were compared using Chi-square test. Results: 399 (43.4%) were classified as LOW and 522 (56.7%) patients as NORMAL. In the LOW group, there were more patients with diabetes, less patients with ICA severe stenosis and opening of anterior/posterior communicating artery. Occurrence of CHS per ultrasonographic criteria was higher in the LOW group (21.3% vs. 15.7%, P=0.03), but similar for clinical CHS criteria group (3.2%, vs 2.1%, p=0.28) and for frequency of perioperative cerebral infarction (5.8% vs.5.0%, p=0.60). Conclusion: Although patients with decreased flow velocities post-GA were more likely to meet ultrasonographic criteria for CHS, there were no differences in clinical CHS criteria. Our results suggest decreased flow velocities post-GA may not associated with incidence of CHS.

Posterior cerebral artery

Stroke

10.1161/str.48.suppl_1.wp134

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Association between blood pressure and intracranial artery stenosis in a Chinese population

Journal of Clinical Hypertension (2019)

Xiaowei Song Qiannan Zhao Hua Yang Chunxiu Wang Beibei Liu

Abstract The association between blood pressure and intracranial artery stenosis (ICAS) in different age groups has not been elucidated. Using data from the “China Hypertension Survey,” we conducted a cross‐sectional analysis of the association between blood pressure parameters and ICAS. In this study, participants older than 35 years were selected by stratified, multistage random sampling. Blood pressure was measured repeatedly at rest, and ICAS was assessed by transcranial doppler ultrasound. Binary logistic regression analysis was used to demonstrate the association between different blood pressure indicators and ICAS. Of the 3640 participants included (mean age 63 ± 13 years old, 57.8% female), systolic blood pressure (SBP) and pulse pressure (PP) were associated with ICAS in the general population; the multivariable adjusted odds ratio (OR) and corresponding 95% confidence interval (95% CI) of ICAS and multivessel stenosis were 1.32 (1.21, 1.45) and 1.29 (1.14, 1.46) per standard deviation (SD) increase in SBP and 1.44 (1.30, 1.59) and 1.52 (1.33, 1.74) for PP, respectively. Further analysis of this association in different age groups revealed inconsistent results between SBP and ICAS. Prehypertension (120 ≤ SBP < 140) could predict ICAS in the older group but not in the younger group, and the positive association between SBP and multivessel stenosis disappeared in the younger age group ( P > .05 in all SBP subgroups). In conclusion, SBP and PP could not only identify ICAS in the middle‐aged and elderly population but could also provide some information about ICAS burden; however, these associations need to be interpreted differentially based on age subgroup.

Prehypertension

Transcranial Doppler

Pulse pressure

10.1111/jch.13770

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Correlation Between Calcification Characteristics of Carotid Atherosclerotic Plaque and Plaque Vulnerability

Therapeutics and Clinical Risk Management (2021)

Xiangli Xu Hua Yang Beibei Liu Fubo Zhou Lili Wang

To investigate the relationship between calcification characteristics of carotid atherosclerotic plaque and lipid rich necrotic core (LRNC) and intraplaque hemorrhage (IPH).Patients with severe carotid stenosis undergoing carotid endarterectomy (CEA) were selected. Ultrasound and CT angiography (CTA) were performed to evaluate the calcification characteristics of the plaque before the surgery.A total of 142 patients were included and 142 pathological specimens of postoperative plaque were obtained accordingly. There were 78 plaques (54.9%) with LRNC and 41 (28.9%) with IPH. The plaque with LRNC had higher calcification rate (93.6%) compared with the plaque with IPH (87.8%). LRNC was often found in multiple calcification (P = 0.003) and mixed type calcification (P = 0.001). Multiple calcification was more likely to combine with IPH (P = 0.008), while simple basal calcification was not likely to combine IPH (P = 0.002). Smaller granular calcification was more likely to be associated with IPH (P < 0.05). In multivariate regression analysis of IPH and calcification characteristics, simple basal calcification was still a protective factor for IPH (OR, 0.25; 95% CI, 0.09-0.66; P = 0.005), while multiple calcification was closely related to the occurrence of IPH (OR, 3.58; 95% CI, 1.49-8.61; P = 0.004).Calcification characteristics of carotid atherosclerotic plaques are closely related to the vulnerability of plaques, especially multiple calcification and mixed type calcification.

Fibrous cap

10.2147/tcrm.s303485

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Dynamic Cerebral Autoregulation in Preclinical Atherosclerotic Cardiovascular Disease

Journal of Stroke and Cerebrovascular Diseases (2020)

Yumei Liu Takashi Tarumi Beibei Liu Jingzhi Li Xiaoguang Wu

Cerebral autoregulation

10.1016/j.jstrokecerebrovasdis.2020.104810

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Bimodal Regulation of the PRC2 Complex by USP7 Underlies Melanomagenesis

bioRxiv (Cold Spring Harbor Laboratory) (2019)

Dongxue Su Wenjuan Wang Yongqiang Hou Liyong Wang Yue Wang

ABSTRACT Although overexpression of EZH2, a catalytic subunit of the polycomb repressive complex 2 (PRC2), is an eminent feature of various cancers, the regulation of its abundance and function remains insufficiently understood. We report here that the PRC2 complex is physically associated with ubiquitin-specific protease USP7 in melanoma cells where USP7 acts to deubiquitinate and stabilize EZH2. Interestingly, we found that USP7-catalyzed H2BK120 deubiquitination is a prerequisite for chromatin loading of PRC2 thus H3K27 trimethylation. Genome-wide analysis of the transcriptional targets of the USP7/PRC2 complex identified a cohort of genes including FOXO1 that are involved in cell growth and proliferation. We demonstrated that the USP7/PRC2 complex drives melanoma cell proliferation and tumorigenesis in vitro and in vivo. We showed that the expression of both USP7 and EZH2 elevates during melanoma progression, corresponding to a diminished FOXO1 expression, and the level of the expression of USP7 and EZH2 strongly correlates with histological grades and prognosis of melanoma patients. These results reveal a dual role for USP7 in the regulation of the abundance and function of EZH2, supporting the pursuit of USP7 as a therapeutic target for melanoma.

PRC2

10.1101/641977

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Oxidized albumin is a risk factor for chronic kidney disease

Research Square (Research Square) (2023)

Beibei Liu Suzhi Chen Bingfeng Li

Abstract Background Oxidized albumin plays a role in various animal disease models, including diabetes and aging. Oxidized albumin has been identified as a novel biomarker of oxidative stress. In this study, rat chronic kidney disease model with proteinuria and hypertension caused by high levels of oxidative stress was utilized. Methods A Total of 24-Male-Sprague Dawley rats were randomly assigned for 4 weeks to one of four groups: normal control group (Con, n = 6), normal salt-treated 5/6 nephrectomy (ND, n = 6), high salt-loading 5/6 nephrectomy (HSD, n = 6), and Tempol-loading 5/6 nephrectomy (HSD + Tempol, n = 6). All animals were sacrificed at the conclusion of the research process. Urine samples, blood samples, and kidney tissues were collected for checking proteinuria, serum creatinine, urea, α-SMA, malondialdehyde (MDA), and histopathology study. Results Blood pressure, urinary protein, plasma creatinine, BUN, α-SMA, malondialdehyde (MDA) levels were significantly higher the high salt diet group than in the normal salt loading diet group, and the effects of the aforesaid parameters were reversed following treatment with Tempol. Conclusions In 5/6 nephrectomized CKD rat model, high salt diet tended to increase the levels of blood pressure, urinary protein, serum creatinine, urea, malondialdehyde (MDA) levels, and expression of α-SMA. Additionally, Tempol tends to ameliorate the severity of fibrosis and oxidative stress in the remaining kidney.

Malondialdehyde

Blood urea nitrogen

10.21203/rs.3.rs-3343629/v1

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Effects of High-Fat Diet on Carcinogen-Induced Pancreatic Cancer and Intestinal Microbiota in C57BL/6 Wild-Type Mice

Pancreas (2021)

Beibei Liu Furong Wang Lina Chen Yi Xin Likun Liu

Objectives High-fat diet has been considered a risk factor for the development of pancreatic cancer. It is also shown to significantly impact composition and dysbiosis of gut microbiota in both humans and animals. However, there is little information on the effect of high-fat diet on the development of pancreatic cancer or upon the gut microbiota of patients with pancreatic cancer in humans or animal models. Methods In this study, the effect of high-fat diet on cancer pathology and the gut microbiota was investigated by a carcinogen-induced pancreatic cancer mouse model. Results Compared with carcinogen alone, mice with high-fat diet and carcinogen showed more obvious pathological changes in pancreatic tissue; increased levels of proinflammatory cytokine tumor necrosis factor-α, interleukin-6, interleukin-10, and carbohydrate antigen 242; and increased expression of cancer-associated biomarkers mucin-4 and claudin-4 in pancreatic tissue. Moreover, there is a significant change in the gut microbiota between the carcinogen group and the carcinogen with high-fat diet group. We identified that Johnsonella ignava especially existed in the carcinogen with high-fat diet group, which may contribute to pancreatic cancer development. Conclusions Our results revealed that high-fat diet changed the composition of the gut microbiota and was involved in carcinogen-induced pancreatic cancer progression.

Proinflammatory cytokine

10.1097/mpa.0000000000001797

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Intracellular galectin-3 is a lipopolysaccharide sensor that promotes glycolysis through mTORC1 activation

Nature Communications (2022)

Xing Chen Chunyu Yu Xinhua Liu Beibei Liu Xiaodi Wu

Abstract How the carbohydrate binding protein galectin-3 might act as a diabetogenic and tumorogenic factor remains to be investigated. Here we report that intracellular galectin-3 interacts with Rag GTPases and Ragulator on lysosomes. We show that galectin-3 senses lipopolysaccharide (LPS) to facilitate the interaction of Rag GTPases and Ragulator, leading to the activation of mTORC1. We find that the lipopolysaccharide/galectin-3-Rag GTPases/Ragulator-mTORC1 axis regulates a cohort of genes including GLUT1 , and HK2 , and PKM2 that are critically involved in glucose uptake and glycolysis. Indeed, galectin-3 deficiency severely compromises LPS-promoted glycolysis. Importantly, the expression of HK2 is significantly reduced in diabetes patients. In multiple types of cancer including hepatocellular carcinoma (HCC), galectin-3 is highly expressed, and its level of expression is positively correlated with that of HK2 and PKM2 and negatively correlated with the prognosis of HCC patients. Our study unravels that galectin-3 is a sensor of LPS, an important modulator of the mTORC1 signaling, and a critical regulator of glucose metabolism.

10.1038/s41467-022-35334-x

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Brown Adipose Tissue Activation Is Involved in Atherosclerosis of ApoE−/− Mice Induced by Chronic Intermittent Hypoxia

Frontiers in Cardiovascular Medicine (2021)

Yue Wang Hongfeng Jiang Beibei Liu Leilei Chen Yue Wang

Background: Obstructive sleep apnea is an atherogenesis factor of which chronic intermittent hypoxia is a prominent feature. Chronic intermittent hypoxia (CIH) exposure can sufficiently activate the sympathetic system, which acts on the β3 adrenergic receptors of brown adipose tissue (BAT). However, the activity of BAT and its function in CIH-induced atherosclerosis have not been fully elucidated. Methods: This study involved ApoE-/- mice which were fed with a high-fat diet for 12 weeks and grouped into control and CIH group. During the last 8 weeks, mice in the CIH group were housed in cages to deliver CIH (12 h per day, cyclic inspiratory oxygen fraction 5-20.9%, 180 s cycle). Atherosclerotic plaques were evaluated by Oil Red O, hematoxylin and eosin, Masson staining, and immunohistochemistry. Afterward, we conducted immunohistochemistry, western blotting, and qRT-PCR of uncoupling protein 1 (UCP1) to investigate the activation of BAT. The level of serum total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and free fatty acid (FFA) were measured. Finally, RNA-Sequencing was deployed to explore the differentially expressed genes (DEGs) and their enriched pathways between control and CIH groups. Results: Chronic intermittent hypoxia exposure promoted atherosclerotic plaque area with increasing CD68, α-SMA, and collagen in plaques. BAT activation was presented during CIH exposure with UCP1 up-regulated. Serum TC, triglyceride, LDL-c, and FFA were increased accompanied by BAT activation. HDL-c was decreased. Mechanistically, 43 lipolysis and lipid metabolism-associated mRNA showed different expression profiling between the groups. Calcium, MAPK, and adrenergic signaling pathway included the most gene number among the significantly enriched pathways. Conclusion: This study first demonstrated that BAT activation is involved in the progression of CIH-induced atherosclerosis, possibly by stimulating lipolysis.

Oil Red O

Intermittent hypoxia

Hypoxia

10.3389/fcvm.2021.751519

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Gender-specific relationship between frequency of food-away-from-home with serum lipid levels and dyslipidemia in chinese rural adults

Lipids in Health and Disease (2022)

Yuyang Wang Xiaotian Liu Xiaokang Dong Beibei Liu Ning Kang

Abstract Objective Food-away-from-home (FAFH) is one of the leading dietary patterns in Chinese families. However, the relationship between FAFH and dyslipidemia remains unclear, especially in the rural adult population. This study explored the relationship of FAFH frequency with serum lipid levels and dyslipidemia in rural Chinese adults. Methods A total of 12,002 men and 17,477 women aged 18–79 were included from the Henan rural cohort. Serum lipid levels were measured by enzyme colorimetry. Information on FAFH frequency was collected using a validated questionnaire. The associations of FAFH frequency and serum lipid levels were assessed through multiple linear regression modeling. Logistic regression was performed to explore the linkages of the FAFH frequency to dyslipidemia and its four parameter types. Mediation analysis examined whether body mass index (BMI) acted as a mediator between the FAFH frequency and dyslipidemia. Results After adjusting for potential confounders, the adjusted odds ratio ( OR ) and 95% confidence interval ( CI ) of the groups with 8–11 FAFH times/week for dyslipidemia were 1.991 (1.569, 2.526) in men compared with 0-frequency subgroup. Participants who consumed 8–11 FAFH times/week had a higher risk of high total cholesterol (TC), high triglycerides (TG), high LDL-cholesterol (LDL-C), and low HDL-cholesterol (HDL-C) with the OR and 95% CI of 1.928 (1.247, 2.980), 1.723 (1.321, 2.247), 1.875 (1.215, 2.893), and 1.513 (1.168, 1.959), respectively. In addition, the interaction effect between FAFH and gender was significantly associated with dyslipidemia and lipid levels ( P < 0.001). BMI played a fully mediating effect between FAFH frequency and dyslipidemia in men, and the Sobel test showed the significance of the mediating effect (z = 4.2158, P < 0.001). Conclusion In rural Chinese adults, FAFH was significantly associated with a higher risk of dyslipidemia, which indicated the importance of FAFH reduction and dietary intervention in patients with dyslipidemia and cardiovascular disease, especially in clinical practice. Trial Registration The Henan Rural Cohort Study has been registered on the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15,006,699).

Dyslipidemia

Clinical nutrition

10.1186/s12944-022-01719-6

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