1.Oligodendrocyte dysfunction in cerebral ischemia and neurodegenerative disorders:the effect of CysLT receptor antagonists
Yuqing LIAO ; Chengtan LI ; Yanfang WANG ; Lihui ZHANG
Chinese Journal of Pharmacology and Toxicology 2023;37(7):504-504
Ischemic stroke is an acute and serious cerebrovascular accident.Neurodegenerative disorders are characterized by progressive degeneration of neu-rons in the central nervous system(CNS),resulting in severe disability and death.Myelin is essential for the health and function of neuronal axons.Oligodendrocytes,the myelinating cells of CNS,are vulnerable to ischemia and neurodegenerative disorders.G protein-coupled receptor 17(GPR17)is a dual receptor activated by uracil nucleotides/cysteinyl leukotrienes(CysLTs).Abnormal GPR17 activation contributes to oligodendrocyte dysfunc-tion and axonal damage.Gelosa et al.reported that CysLT1 receptor antagonist montelukast increased the recruitment and proliferation of oligodendrocyte precursor cells(OPCs)at the acute phase after ischemic stroke.Similarly,a study showed that montelukast stimulated neural progenitor proliferation and hippocampal neuro-genesis of aged rats through inhibition of GPR17.These results were supported by several studies on neurode-generative diseases.The authors showed that pharmaco-logical blockade of GPR17 with CysLT1 or CysLT2 recep-tor antagonists(montelukast or HAMI3379)improved oli-godendrocyte function and fiber connectivity,highlighting GPR17 as a potential therapeutic target in oligodendro-cyte protection and remyelination.Recently,growing evi-dence has revealed a significant interaction between mi-croglia and oligodendrocytes in CNS injury and disease.It was reported that M2 microglia promoted,while M1 microglia inhibited oligodendrogenesis,OPCs maturation and remyelination.Microglia-mediated neuroinflamma-tion,considered as an important pathological event,neg-atively affected OPCs fate and function in experimental neurological disorders.This was further corroborated by later studies.It was recently reported that montelukast enhanced OPCs differentiation and maturation by upreg-ulating the number of M2 microglia at chronic phase of brain ischemia.In line with the above results,inhibition of microglial inflammation by montelukast was shown to be responsible for neurite outgrowth.Although the exact mechanisms were not fully clarified,these results indi-cate that montelukast may indirectly promote OPCs dif-ferentiation and remyelination by a microglia-dependent manner.It has been widely accepted that CysLT1,CysLT2 and GPR17 receptors are localized in various cell types and their expression are upregulated after brain damage.Therefore,it is likely that CysLT receptor antagonists confer neuroprotection by targeting different receptors and multiple cell functions.Many studies have reported that CysLT receptor antagonists promote protec-tion of oligodendrocytes by inhibiting GPR17.Moreover,they may improve OPCs differentiation and neuronal sur-vival by regulating CysLTs-mediated microglial activation.Altogether,these data open novel perspectives in the treatment of cerebral ischemia and neurodegenerative diseases.
2.Analysis of potential diagnostic genes for eosinophilic chronic rhinosinusitis with nasal polyps based on GEO datasets
Yuqing HUANG ; Chen MENG ; Jianhong LIAO ; Bing YAN ; Luo ZHANG ; Chengshuo WANG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2023;30(12):781-784
OBJECTIVE To utilize RNA sequencing(RNA-seq)data from the GEO database to identify genes with potential diagnostic value for eosinophilic chronic rhinosinusitis with nasal polyps(ECRSwNP).METHODS Three datasets were obtained,and samples were divided into ECRSwNP and nonECRSwNP groups based on the expression levels of CST1 and CLC.A diagnostic model for ECRSwNP was established using R software and algorithms,and its accuracy was assessed.RESULTS The samples were grouped as follows:GSE136825(ECRSwNP 7,nonECRSwNP 19),GSE72713(ECRSwNP 3,nonECRSwNP 3),and GSE179265(ECRSwNP 11,nonECRSwNP 2).The diagnostic performance of the upregulated gene model(ADH1C,CCL26,HRH1,NOS2)and the downregulated gene model(LCN2,MUC5B,PLAT,TMEM45A,XDH)constructed based on the support vector machine(SVM)algorithm for ECRSwNP was excellent.CONCLUSION The diagnostic genes identified by the SVM model may serve as biological markers for the non-invasive diagnosis of ECRSwNP and potentially play a crucial role in the pathogenesis of ECRSwNP.
3.Cucurbitacin B-induced G2/M cell cycle arrest of conjunctival melanoma cells mediated by GRP78-FOXM1-KIF20A pathway.
Jinlian WEI ; Xin CHEN ; Yongyun LI ; Ruoxi LI ; Keting BAO ; Liang LIAO ; Yuqing XIE ; Tiannuo YANG ; Jin ZHU ; Fei MAO ; Shuaishuai NI ; Renbing JIA ; Xiaofang XU ; Jian LI
Acta Pharmaceutica Sinica B 2022;12(10):3861-3876
Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a K d value of 0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.
4.Multimodal imaging characteristics of combined hamartoma of the retina and retinal pigment epithelium
Zijing LI ; Yunru LIAO ; Peng ZENG ; Rui ZENG ; Yuqing LAN
Chinese Journal of Ocular Fundus Diseases 2019;35(4):338-341
Objective To observe the multimodal imaging characteristics of combined hamatoma of the retina and retinal pigment epithelium (CHRRPE).Methods A retrospective case study.From January 2013 to December 2017,6 CHRRPE patients (6 eyes) diagnosed in Department of Ophthalmology,Sun Yat-sen Memorial Hospital were included in the study.There were 4 males and 2 females,with the mean age of 12.0±8.10 years.There were 5 eyes with BCVA ≤0.1,1 eye with BCVA> 1.0.Corneal fluoroscopy showed 1 eye with an external oblique 15°,and the remaining eye had no abnormalities in the anterior segment.All eyes underwent fundus color photography,FAF,FFA,ICGA,OCT and color Doppler flow imaging (CDFI).The multimodal imaging characteristics were observed.Results All the affected eyes CHRRPE were located in the posterior pole and showed mild elevation.Most of the retinal neuroepithelial layers had different degrees of hyperplasia,vascular tortuosity and retinal folds.Of the 6 eyes,4 eyes (66.7%) involving the macula and optic disc,only 2 eyes (33.3%) involving the macula.OCT showed that the structure of the neuroepithelial layer was unclear and the signal intensity was uneven;it involved 2 eyes of the whole retina (33.3%) and only 4 eyes of the neuroepithelial layer (66.7%).FFA and ICGA showed that the choroidal background fluorescence of the early lesions was weakened,and the lesions showed slightly weak fluorescence;the late telangiectasia fluorescein was obviously leaked,and the lesions were stained with fluorescence.FAF mainly appears as weak autofluorescence with a small amount of strong autofluorescence.CDFI has no characteristic performance.Conclusions CHRRPE is mainly a membrane-like hyperplasia without angiogenesis,involving the retinal neuroepithelial layer,and may also involve the entire retina.OCT is dominated by strong reflection;AF,FFA and ICGA are mainly weak fluorescence.
5.Study on the relationship between left atrial diameter with serum uric acid level in male patients with essential hypertension
Xuan LIAO ; Xueju YU ; Dan ZHOU ; Yuqing HUANG
Chinese Journal of Primary Medicine and Pharmacy 2018;25(14):1769-1772
Objective To study the relationship between serum uric acid and left atrial size in male patients with essential hypertension.Methods From June 2015 to December 2016,298 males with essential hypertension in the People's Hospital of Guangdong Province were selected.They were divided into normal left atrial group and enlarged left atrial group based on the size of left atrial diameter.The fasting blood glucose,serum lipid,serum uric acid,hepatic and renal function and blood pressure were measured by routine methods,and multivariate logistic regres-sion was used to analyze.Results The average age and serum uric acid level of 298 males with essential hypertension were (55.29 ±8.48)years old and (488.93 ±112.46)μmol/L.There were 47 cases with enlarged left atrial.The serum uric acid level in the enlarged left atrial group was significant higher than that in the normal left atrial group [(512.21±90.82 )μmol/L vs.(474.38 ±94.26 )μmol/L,t =9.34,P<0.001].Pearson correlation analysis showed that serum uric acid level was positively associated with left atrial diameter(r=0.589,P<0.001).Multiple logistic regression analysis showed that the serum uric acid level was a risk factor for enlarged left atrial(OR=1.894, 95%CI:1.13,2.69;P<0.001).Conclusion Serum uric acid level is positively correlated with left atrial size in male patients with essential hypertension,and is a risk factor for enlarged left atrial.
6.Cognitive functions in patients with depressive disorder,hyperlipidemia disorder, and comorbid both of the disorders
Yuqing SONG ; Hongguang CHEN ; Jinmin LIAO ; Han ZHANG ; Manman CHEN ; Xilin WANG
Chinese Mental Health Journal 2018;32(2):112-117
Objective:To compare the cognitive functions in patients with depressive disorder,hyperlipidemia disorder,and comorbid both of the disorders.Methods:A cross-sectional study was performed in age,gender and education year matched patients with depressive disorder (n =51)(according to the ICD-10),hypedipidemia(n =38) (according to the Chinese adult lipid guideline),comorbid both of the disorders(n =40) and normal controls (n =56) were recruited in this study.All subjects received a battery of neuropsychological tests to access the anxiety and depression symptoms and cognitive function.Results:The scores of MoCA were lower in the patients with comorbid both disorders and patients with depression than patients with hypedipidemia [(24 ± 3),(24 ± 4)vs.(26 ± 3),Ps <0.05],and were lower in patients with depression than in normal controls(25 ±3),P <0.05.Stroop color test amends numbers were higher in patients with comorbid disorder than in the other three groups (Ps <0.05).The scores of immediate and delayed logical memory were higher in patients with hyperlipidemia than in other three groups (Ps <0.05).The total number of words in verbal fluency test were lower in patients with comorbid disorders and patients with depression than in patients with hyperlipidemia (Ps <0.05).Wisconsin card sorting test category completes were lower in patients with comorbid disorders and patients with depression than in patients with hyperlipidemia and normal controls (Ps < 0.05).The scores of persistent errors were higher in patients with comorbid disorders and patients with depression than in patients with hyperlipidemia and normal controls (Ps <0.05).Conclusion:In this study,patients with depressive disorder have impairment of cognitive function,while hyperlipidemia may probably do not impair cognitive function.
7.The Oral Microbiome Bank of China.
Peng XIAN ; Zhou XUEDONG ; Xu XIN ; Li YUQING ; Li YAN ; Li JIYAO ; Su XIAOQUAN ; Huang SHI ; Xu JIAN ; Liao GA
International Journal of Oral Science 2018;10(2):16-16
The human microbiome project (HMP) promoted further understanding of human oral microbes. However, research on the human oral microbiota has not made as much progress as research on the gut microbiota. Currently, the causal relationship between the oral microbiota and oral diseases remains unclear, and little is known about the link between the oral microbiota and human systemic diseases. To further understand the contribution of the oral microbiota in oral diseases and systemic diseases, a Human Oral Microbiome Database (HOMD) was established in the US. The HOMD includes 619 taxa in 13 phyla, and most of the microorganisms are from American populations. Due to individual differences in the microbiome, the HOMD does not reflect the Chinese oral microbial status. Herein, we established a new oral microbiome database-the Oral Microbiome Bank of China (OMBC, http://www.sklod.org/ombc ). Currently, the OMBC includes information on 289 bacterial strains and 720 clinical samples from the Chinese population, along with lab and clinical information. The OMBC is the first curated description of a Chinese-associated microbiome; it provides tools for use in investigating the role of the oral microbiome in health and diseases, and will give the community abundant data and strain information for future oral microbial studies.
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8.Genetic polymorphism of rs9574 C/G of endothelial cell protein C receptor gene in Guangxi population
Yanbing LIANG ; Dingwei PENG ; Yuqing HUANG ; Yesheng WEI ; Weigui LUO ; Jun LI ; Pinhu LIAO
Chinese Journal of Clinical and Experimental Pathology 2017;33(3):249-252
Purpose To compare the difference of the genotype and allele of endothelial cell protein C receptor (EPCR)gene rs9574 C/G between Guangxi population and other ethnic groups.Methods The rs9574 C/G polymorphisms of EPCR in 130 cases of Guangxi population were detected by PCR and DNA sequencing.The distribution frequency of allele and genotype was compared with the other four ethnic groups (HapMap-CEU,HapMap-HCB,HapMap-JPT,HapMap-YRI),which was published by the human genome project.Results Three genotypes of CC,CT and TT were found in rs9574 C/G with the frequencies of 39.2%,46.2%,14.6% respectively.the allele frequencies of C,T were 62.3% and 37.7%.No significant difference was observed in the frequency of genotype and allele between male and female (P > 0.05).There were significant differences in the genotype distribution among Guangxi population,HapMap-CEU and HapMap-YRI (P < 0.05).Significant differences of allelic frequency were found among Guangxi population,HapMap-CEU,HapMap-JPT and HapMap-YRI.Condusion The polymorphisms of rs9574C/G in 3'-noncoding region of EPCR gene in Guangxi population were different in different regions and ethnic groups.
9.Application value of 3D printing technology in the surgery of sphenoid ridge meningioma
LIU YUQING ; HE BINGWEI ; HUANG SHENGYUE ; YANG ZHIKUN ; ZHUANG JIANGHUI ; CHEN MINGWU ; CHEN SHOU ; LIAO ZHENGJIAN
Chinese Journal of Clinical Oncology 2017;44(22):1146-1150
Objective:To investigate the value of 3D printing technology in sphenoid ridge meningioma dissection. Methods:By using craniocerebral spiral enhanced CT scan DICOM images, the skull, vessels, and tumor were extracted, reconstructed, and assembled and integrated in the same coordinate system. Then, we constructed a 3D virtual model and a 3D-printed entity model, which was ap-plied for preoperation and postoperation. Results:Virtual models of the brains of five patients were reconstructed successfully and 3D entity models were produced. The models expressed the relationship among tumors, adjacent blood vessels, and the important posi-tion of the nerve tissue. Then, the models were applied to the reference before surgery planning and after surgery. Five cases were successfully performed. Conclusion:The use of the entity model of sphenoid ridge meningioma is important in optimizing operation plans, improving tumor resection, and reducing intraoperative bleeding.
10.The effects of low-dose theophylline and tiotropium on lung function and quality of life in patients with mild-moderate stable chronic obstructive pulmonary disease
Yuqing CHEN ; Ruomin LIAO ; Hongbing XU ; Xin ZHOU
Chinese Journal of Postgraduates of Medicine 2015;38(4):235-240
Objective To observe the effects of low-dose theophylline and tiotropium on lung function and quality of life in patients with mild-moderate stable chronic obstructive pulmonary disease (COPD) and evaluate its safety.Methods This was a randomized,parallel-group,controlled trial.A total of 115 patients with mild-moderate stable COPD were divided into tiotropium group (37 cases),slow-release theophylline group (40 cases) and the combination of slow-release theophylline and tiotropium group (38 cases) by random digits table method.Thirty-eight patients without cardiopulmonary diseases were enrolled in control group.Observation period was 12 months.The lung function,6 min walking test distance (6MWD),modified British Medical Research Council Scale (mMRC),and COPD assessment test (CAT) were monitored before treatment and after treatment for 12 months.Results Of 115 patients,107 patients (35cases in tiotropium group,36 cases in slow-release theophylline group and 36 cases in combination of slowrelease theophylline and tiotropium group) completed the study.No significant difference was found in spirometry parameters reflecting airflow limitation after 12 months treatment compared with that before treatment in tiotropium group,slow-release theophylline group and the combination of slow-release theophylline and tiotropium group (P > 0.05),such as the percentage of forced expiratory volume in 1 second (FEV1) over the expected value (FEV1%) and FEV1/forced vital capacity (FVC).The percentage of mid expiratory flow over the expected value (FEF25~75%) was improved in all groups,but the increment of FEF25~75 % was much higher in tiotropium group and the combination of slow-release theophylline and tiotropium group than that in slow-release theophylline group:(39.23 ± 7.77)%,(39.99 ± 8.25)% vs.(34.91 ± 9.50)%,there were significant differences (P < 0.05).Similar changes were observed in mMRC and CAT score.There was significant difference in CAT score between tiotropium group,the combination of slow-release theophylline and tiotropium group and slow-release theophylline group:(14.34 ± 2.22),(14.39 ± 3.53) scores vs.(16.22 ± 3.35) scores,P < 0.05.6MWD was no obvious change in tiotropium group,slow-release theophylline group and the combination of slow-release theophylline and tiotropium group before and after treatment.The use frequency of short-acting drugs bronchiectasis was the lowest in the combination of slow-release theophylline and tiotropium group,and only was (2.3 ± 1.4) times per week.Fourteen patients happened COPD exacerbations in slow-release theophylline group during 12 months treatment.The duration in slow-release theophylline group was more than that in tiotropium group and the combination of slow-release theophylline and tiotropium group:(9.76 ± 2.25) d vs.(7.85 ± 2.51),(8.29 ± 2.24) d,and there was significant difference (P < 0.05).Conclusions For mild-moderate stable COPD patients,the quality of life and dyspnea scores are not improved significantly after treatment of low-dose slow-release theophylline,and the combination slow-release theophylline and tiotropium may be more beneficial and safe.

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