Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease

Xiong Liu-Lin,Xue Lu-Lu,Du Ruo-Lan,Niu Rui-Ze,Chen Li,Chen Jie,Hu Qiao,Tan Ya-Xin,Shang Hui-Fang,Liu Jia,Yu Chang-Yin,Wang Ting-Hua 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.

Aberrant DNA Methylation of P16, MGMT, hMLH1 and hMSH2 Genes in Combination with the MTHFR C677T Genetic Polymorphism in Gastric Cancer

Xiong, Hai-Lin,Liu, Xun-Qi,Sun, Ai-Hua,He, Ying,Li, Jun,Xia, Yuan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Associations of P16, MGMT, hMLH1 and hMLH2 with gastric cancer and their relation with MTHFR status in gastric patients who were confirmed with pathological diagnosis were assessed. Aberrant DNA methylation of P16, MGMT, hMLH1 and hMLH2 and polymorphisms of MTHFR C677T were assayed. The proportional DNA hypermethylation in P16, MGMT, hMLH1 and hMLH2 in cancer tissues was significantly higher than in remote normal-appearing tissues. DNA hypermethylation of P16 and MGMT was correlated with the T and N stages. Individuals with homozygotes (TT) of MTHFR C677T had significant risk of hypermethylation of MGMT in cancer tissues [OR (95% CI)= 3.47(1.41-7.93)]. However, we did not find association between polymorphism in MTHFR C677T and risk of hypermethylation in P16, MGMT, hMLH1 and hMLH2 genes either in cancer or remote normal-appearing tissues. Aberrant hypermethylation of P16, MGMT, hMLH1 and hMLH2 could be predictive of gastric cancer.

Characteristics of Diprophylline-Induced Bidirectional Modulation on Rat Jejunal Contractility

Liu, Fang-Fei,Chen, Da-Peng,Xiong, Yong-Jian,Lv, Bo-Chao,Lin, Yuan The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.1

In this study, we propose that diprophylline exerts bidirectional modulation (BM) on the isolated rat jejunal segment depending on its contractile state. The results supported the hypothesis. Diprophylline ($20{\mu}M$) exerted stimulatory effects on the contractility of jejunal segment in six low contractile states while inhibitory effects in six high contractile states, showing the characteristics of BM. Diprophylline-induced stimulatory effect was significantly blocked by atropine, indicating the correlation with cholinergic activation. Diprophylline-induced inhibitory effect was partially blocked by phentolamine, propranolol, and L-N-Nitro-Arginine respectively, indicating their correlation with sympathetic activation and nitric oxide-mediated relaxing mechanisms. Diprophylline-induced BM was abolished by tetrodotoxin or in a $Ca^{2+}$ free condition or pretreated with tyrosine kinase inhibitor imatinib, suggesting that diprophylline-induced BM is $Ca^{2+}$ dependent, and that it requires the presence of enteric nervous system as well as pacemaker activity of interstitial cells of Cajal. Diprophylline significantly increased the reduced MLCK expression and myosin extent in constipation-prominent rats and significantly decreased the increased MLCK expression and myosin extent in diarrhea-prominent rats, suggesting that the change of MLCK expression may also be involved in diprophylline-induced BM on rat jejunal contractility. In summary, diprophylline-exerted BM depends on the contractile states of the jejunal segments, requires the presence of $Ca^{2+}$, enteric nervous system, pacemaker activity of interstitial cells of Cajal, and MLCK-correlated myosin phosphorylation. The results suggest the potential implication of diprophylline in relieving alternative hypo/hyper intestinal motility.

Circulating MiRNA-21-enriched extracellular vesicles promote bone remodeling in traumatic brain injury patients

Lin Ze,Xiong Yuan,Sun Yun,Zeng Ruiyin,Xue Hang,Hu Yiqiang,Chen Lang,Liu Guodong,Panayi Adriana C.,Zhou Wu,Cao Faqi,Gao Fei,Mi Bobin,Liu Guohui 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Fracture combined with traumatic brain injury (TBI) is one of the most common and serious types of compound trauma in the clinic and is characterized by dysfunction of cellular communication in injured organs. Our prior studies found that TBI was capable of enhancing fracture healing in a paracrine manner. Exosomes (Exos), as small extracellular vesicles, are important paracrine vehicles for noncell therapy. However, whether circulating Exos derived from TBI patients (TBI-Exos) regulate the prohealing effects of fractures remains unclear. Thus, the present study aimed to explore the biological effects of TBI-Exos on fracture healing and reveal the potential molecular mechanism. TBI-Exos were isolated by ultracentrifugation, and the enriched miR-21-5 p was identified by qRT‒PCR analysis. The beneficial effects of TBI-Exos on osteoblastic differentiation and bone remodeling were determined by a series of in vitro assays. Bioinformatics analyses were conducted to identify the potential downstream mechanisms of the regulatory effect of TBI-Exos on osteoblasts. Furthermore, the role of the potential signaling pathway of TBI-Exos in mediating the osteoblastic activity of osteoblasts was assessed. Subsequently, a murine fracture model was established, and the effect of TBI-Exos on bone modeling was demonstrated in vivo. TBI-Exos can be internalized by osteoblasts, and in vitro, suppression of SMAD7 promoted osteogenic differentiation, whereas knockdown of miR-21-5 p in TBI-Exos strongly inhibited this bone-beneficial effect. Similarly, our results confirmed that preinjection of TBI-Exos led to enhanced bone formation, whereas knockdown of exosomal miR-21-5 p substantially impaired this bone-beneficial effect in vivo.

Appraisal of Guidelines for the Management of Blood Pressure in Patients with Diabetes Mellitus: The Consensuses, Controversies and Gaps

Menghui Liu,Shaozhao Zhang,Xiaohong Chen,Yue Guo,Xiangbin Zhong,Zhenyu Xiong,Yifen Lin,Huimin Zhou,Yiquan Huang,Zhengzhipeng Zhang,Lichun Wang,Xiaodong Zhuang,Xinxue Liao 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.5

Background: Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations.Methods: Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.Results: In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P<0.001). Most of the guidelines advocated systolic BP targets <130 mm Hg (12 guidelines, 60%) and diastolic BP targets <80 mm Hg (14 guidelines, 70%) in DM patients. Approximately half of the guidelines supported systolic BP thresholds >140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients.Conclusion: The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.

An Enhanced Biometric-Based Three Factors User Authentication Scheme for Multi-server Environments

Youping Lin,Kaihui Wang,Baocan Zhang,Yuzhen Liu,Xiong Li 보안공학연구지원센터 2016 International Journal of Security and Its Applicat Vol.10 No.1

Authentication is an important and basic security service for many network based applications, which allows the registered user access remote services after the validity of his/her identity is verified by the remote server. Password, smart card and biometric are three frequently used factors in authentication, and some remote user authentication schemes for different environments had been presented based on these factors by researchers. Recently, Baruah et al. pointed out the weaknesses of Mishra et al.’s three factors user authentication scheme for multi-server environments, and they proposed an enhanced scheme. They claimed that their scheme has many security features and can resist some common attacks. However, based on our analysis, Baruah et al.’s scheme cannot resist stolen smart card attack, cannot protect user’s anonymity, and it is also vulnerable to Denial of Service attack. In this paper, an enhanced three factors user authentication scheme for multi-server environments based on fuzzy extractor technology is proposed, and the analysis show that the proposed scheme is more security and efficient than other related schemes.

Novel Coronavirus Pneumonia Outbreak in 2019: Computed Tomographic Findings in Two Cases

Xiaoqi Lin,Zhenyu Gong,Zuke Xiao,Jingliang Xiong,Bing Fan,Jiaqi Liu 대한영상의학회 2020 Korean Journal of Radiology Vol.21 No.3

Since the 2019 novel coronavirus (2019-nCoV or officially named by the World Health Organization as COVID-19) outbreak in Wuhan, Hubei Province, China in 2019, there have been a few reports of its imaging findings. Here, we report two confirmed cases of 2019-nCoV pneumonia with chest computed tomography findings of multiple regions of patchy consolidation and ground-glass opacities in both lungs. These findings were characteristically located along the bronchial bundle or subpleural lungs.

The Arabidopsis callose synthase gene GSL8 is required for cytokinesis and cell patterning.

Chen, Xiong-Yan,Liu, Lin,Lee, Eunkyoung,Han, Xiao,Rim, Yeonggil,Chu, Hyosub,Kim, Seon-Won,Sack, Fred,Kim, Jae-Yean American Society of Plant Physiologists 2009 Plant Physiology Vol.150 No.1

<P>Cytokinesis is the division of the cytoplasm and its separation into two daughter cells. Cell plate growth and cytokinesis appear to require callose, but direct functional evidence is still lacking. To determine the role of callose and its synthesis during cytokinesis, we identified and characterized mutants in many members of the GLUCAN SYNTHASE-LIKE (GSL; or CALLOSE SYNTHASE) gene family in Arabidopsis (Arabidopsis thaliana). Most gsl mutants (gsl1-gsl7, gsl9, gsl11, and gsl12) exhibited roughly normal seedling growth and development. However, mutations in GSL8, which were previously reported to be gametophytic lethal, were found to produce seedlings with pleiotropic defects during embryogenesis and early vegetative growth. We found cell wall stubs, two nuclei in one cell, and other defects in cell division in homozygous gsl8 insertional alleles. In addition, gsl8 mutants and inducible RNA interference lines of GSL8 showed reduced callose deposition at cell plates and/or new cell walls. Together, these data show that the GSL8 gene encodes a putative callose synthase required for cytokinesis and seedling maturation. In addition, gsl8 mutants disrupt cellular and tissue-level patterning, as shown by the presence of clusters of stomata in direct contact and by islands of excessive cell proliferation in the developing epidermis. Thus, GSL8 is required for patterning as well as cytokinesis during Arabidopsis development.</P>

The characteristics of genistin-induced inhibitory effects on intestinal motility

Yong-jian Xiong,Da-peng Chen,Bo-chao Lv,Fang-fei Liu,Li Wang,Yuan Lin 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.3

Genistin belongs to isoflavones. Based on thefacts that genistin exerts inhibitory effects on the contractilityof vascular smooth muscle,the present study wasdesigned to characterize the effects of genistin on intestinalcontractility and evaluate its potential clinical implication. Ex vivo [isolated jejunal segment (IJS) of rat], in vitro, andin vivo assays were used in the study. The results indicatedthat genistin (5–80 lmol/L) inhibited the contraction of IJSin a dose-dependent manner and inhibited the increasedcontractilityof IJS induced by acetylcholine (ACh), histamine,high Ca2?, and erythromycin, respectively. Theinhibitory effects of genistin were correlated with thestimulation of alpha adrenergic and beta adrenergicreceptors since these inhibitory effects were significantlyblocked in the presence of phentolamine and propranololrespectively. No further inhibitory effects of genistin wereobserved in the presence of verapamil or in Ca2?-freecondition, indicating genistin-induced inhibitory effects areCa2?-dependent. Genistin decreased myosin light chainkinase (MLCK) protein contents and MLCK mRNAexpression in IJS, and inhibited both phosphorylation andMg2?-ATPase activity of purified myosin, implicating thatthe decrease of MLCK contents and inhibition of MLCKactivity are involved in the genistin-induced inhibitoryeffects. The study suggests the potential clinical implicationsof genistin in relieving intestinal hypercontractility.

Prognostic Significance of Preoperative Serum Alpha-fetoprotein in Hepatocellular Carcinoma and Correlation with Clinicopathological Factors: a Single-center Experience from China

An, Song-Lin,Xiao, Ting,Wang, Li-Ming,Rong, Wei-Qi,Wu, Fan,Feng, Li,Liu, Fa-Qiang,Tian, Fei,Wu, Jian-Xiong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

Objectives: To investigate the prognosis significance of preoperative serum alpha-fetoprotein (AFP) and the correlation with clinicopathological factors of hepatocellular carcinoma (HCC) patients who underwent hepatectomy. Materials and Methods: Clinicopathological data of retrospective analysis were collected for 251 HCC patients undergoing hepatectomy in this study. According to preoperative AFP level, patients were categorized into AFP-negative (0-20ng/mL) and AFP-positive (>20 ng/mL) groups for Kaplan-Meier analysis and Cox proportional hazard regression modeling. Results: The results demonstrated that increased AFP was associated with longer prothrombin time (PTs), liver capsule invasion, low grade differentiation, and late Barcelona Clinic Liver Center (BCLC) stage. Moreover, the female patients had a greater prevalence of increased preoperative AFP than male patients [284.8 (3.975-3167.5) vs (3.653-140.65); Z-2.895, p=0.004]. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 78.1, 57.5, and 40.6 % in the AFP-negative group and 61.8, 37.7, and 31.4 %, respectively, in the AFP-positive group (log-rank test 8.312, p=0.004). The 1-, 3-, and 5-year overall survival (OS) rates were 94.4, 83.8, and 62.3% in the AFP-negative group and 87.2, 60.0, and 36.7%, respectively, in the AFP-positive group. The difference was statistically significant (log-rank test, 16.884, p=0.000). Cox proportional-hazards model identified preoperative AFP to be an independent prognostic predictor of overall survival. Conclusions: Preoperative serum AFP is an independent predictor of prognosis among HCC patients following surgical resection. Female patients have a higher preoperative AFP than their male counterparts.