Publications by authors named "Lizi Jin"

9 Publications

  • Page 1 of 1

Identification of rare heterozygous linkage R965C-R1309H mutations in the pore-forming region of SCN5A gene associated with complex arrhythmia.

Mol Genet Genomic Med 2021 Mar 25:e1613. Epub 2021 Mar 25.

The Cardiovascular Center, Department of Cardiology, Interventional Medical Center, Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.

Background: We examined the genetic background of a Chinese Han family in which some members presented with complex arrhythmias including sick sinus syndrome, progressive conduction block, atrial fibrillation, atrial standstill and Brugada syndrome. The possible underlying mechanism associated with the genetic mutation was explored.

Methods: Targeted capture sequencing was conducted in the probands in the coding and splicing regions of genes implicated in inherited arrhythmias. Stable cell lines overexpressing wild type (WT) or mutant SCN5A were generated in HEK293T cells. Whole-cell recording was performed to evaluate the functional changes in sodium channels.

Results: The rare heterozygous linkage mutations, SCN5A R965C and R1309H, were found in these patients with complex familial arrhythmias. Compared to WT, R965C or R1309H, the peak current of sodium channel was dramatically reduced in HEK293T cell with linkage R965C-R1309H mutation when testing potentials ranging from -45 to 15 mV. Notably, the maximum peak current of sodium channels with R1309H and linkage R965C-R1309H displayed significant decreases of 31.5% and 73.34%, respectively, compared to WT. Additionally, compared to R965C or R1309H alone, the linkage mutation R965C-R1309H demonstrated not only a more obvious depolarisation-shifted activation and hyperpolarisation-shifted inactivation, but also a more significant alteration in the time constant, V and the slope factor of activation and inactivation.

Conclusions: The linkage mutation SCN5A R965C-R1309H led to a more dramatically reduced current density, as well as more significant depolarisation-shifted activation and hyperpolarisation-shifted inactivation in sodium channels than R965C or R1309H alone, which potentially explain this complex familial arrhythmia syndrome.
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http://dx.doi.org/10.1002/mgg3.1613DOI Listing
March 2021

Acute cardiac injury in adult hospitalized COVID-19 patients in Zhuhai, China.

Cardiovasc Diagn Ther 2020 Oct;10(5):1303-1312

Department of Cardiovascular Medicine, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.

Background: Coronavirus disease 2019 (COVID-19) has already became a public health emergency of international concern. COVID-19 related cardiac injury remains largely unclear.

Methods: We retrospectively analyzed demographic, clinical, laboratory and cardiovascular imaging data of all consecutively admitted adult COVID-19 patients in Zhuhai, China from January 17th, 2020 to February 18th, 2020.

Results: A total of 93 patients were included in the study. Acute cardiac injury was found in 9 (9.7%) COVID-19 patients with median level of hypersensitive cardiac troponin I (hs-cTnI) to be 0.085 µg/L (IQR 0.027-0.560 µg/L). Compared with patients without cardiac injury, the median age of patients with cardiac injury was significantly older (65.0 44.0, P<0.05), hypertension was significantly more common (44.4% 14.3%, P<0.05), and the proportion of severe-critical cases were greater (77.8% 17.9%, P<0.05). Patients with cardiac injury were more likely have elevation of N-terminal proBNP (NT-proBNP) in comparison (66.7% 10.0%, P<0.05). There was no significant difference in echocardiographic parameters between patients with and without cardiac injury. Multivariable logistic regression analysis indicated that older age (OR: 1.093, 95% CI: 1.011-1.182) and increased NT-proBNP (OR: 10.979, 95% CI: 2.024-59.555) were independent risk factors for cardiac injury. Cardiac magnetic resonance (CMR) imaging performed on three patients at around one month after they underwent significant hs-cTnI elevation showed that they had underlying cardiovascular comorbidities.

Conclusions: Acute cardiac injury was seen in the minority of hospitalized COVID-19 patients in Zhuhai, China. Older age and increased NT-proBNP were associated with acute cardiac injury.

Registration Number: ChiCTR2000030952.
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http://dx.doi.org/10.21037/cdt-20-607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666934PMC
October 2020

Multiple roles of Ca in the interaction of ciprofloxacin with activated sludge: Spectroscopic investigations of extracellular polymeric substances.

Sci Total Environ 2021 Jan 7;751:142246. Epub 2020 Sep 7.

Department of Environmental Engineering, Zhejiang University, Hangzhou 310058, China. Electronic address:

Calcium ion is an important cation influencing the binding of recalcitrant organic contaminants with activated sludge during wastewater treatment process, but there is still unknown about its role in amphoteric fluoroquinolones binding. Binding experiments show that Ca markedly inhibited binding of ciprofloxacin (CIP) onto sludge, causing 7-203 times of CIP release. Multi-spectroscopic examinations indicate that tryptophan-like and tyrosine-like proteins in extracellular polymeric substances (EPS) were dominant components for CIP binding by static quenching and forming CIP-proteins complexes. Addition of Ca into EPS and CIP binding systems induced increase of association constants (from 0.024-0.064 to 0.027-0.084 L/μmol) and binding constants (from 0.002-0.039 to 0.012-0.107) and decrease of binding sites number (from 0.893-2.007 to 0.721-1.386). Functional groups of EPS and secondary structure of proteins were remarkably changed upon reactions with CIP and Ca. Calcium ion interacted with EPS and CIP binding system in two distinct ways: Ca shielded CO in amide I in EPS for CIP binding, whereas strengthened binding between CIP and functional groups including CO in carboxyl groups in extra-microcolony polymers and OH in extra-cellular polymers by forming ternary complexes. Cation competition for CO in amide I is responsible for Ca induced CIP release from the sludge. Results suggest the highly potential release of CIP from high saline wastewater and cation-conditioned sludge which needs further monitoring and evaluation.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142246DOI Listing
January 2021

Ku80 promotes melanoma growth and regulates antitumor effect of melatonin by targeting HIF1-α dependent PDK-1 signaling pathway.

Redox Biol 2019 07 20;25:101197. Epub 2019 Apr 20.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. Electronic address:

Melanoma is one of the most malignant and aggressive cancers with high cancer-related deaths. However, it is unclear whether Ku80 regulates tumor growth in human melanoma. In this study, we screened a siRNA library targeting 6024 human genes and identified Ku80 as a potential therapeutic target in melanoma cells. Knockdown of Ku80 significantly suppressed melanoma cell proliferation and induced apoptosis, as well as enhanced the antitumor effect of melatonin in melanoma in vitro and in vivo. Overexpression of Ku80, however, promoted melanoma growth and increased the insensitivity of melanoma cells to melatonin. Mechanistically, we found that Ku80 bound to the PDK1 promoter and activated the transcription of PDK1. Moreover, we showed that the binding of Ku80 at the PDK-1 promoter was HIF1-α dependent, and melatonin degraded HIF1-α in melanoma cells. Furthermore, clinical data revealed that the expression of Ku80 and PDK-1 proteins were positively correlated and elevated in the tumor tissues of melanoma patients, and high expression of Ku80 predicted a poor prognosis in melanoma. Collectively, our study demonstrated that Ku80 promoted melanoma growth and regulated antitumor activity of melatonin by targeting HIF1-α dependent PDK-1 signaling pathway, suggesting that Ku80 may be a potential molecular target for melanoma treatment.
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http://dx.doi.org/10.1016/j.redox.2019.101197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859552PMC
July 2019

Sequence-dependent synergistic cytotoxicity of icotinib and pemetrexed in human lung cancer cell lines in vitro and in vivo.

J Exp Clin Cancer Res 2019 Apr 5;38(1):148. Epub 2019 Apr 5.

Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China.

Background: Recent Clinical trials of administration of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with standard first-line chemotherapy have failed to improve survival in patients with advanced NSCLC, However, the sequential treatment with EGFR-TKIs and chemotherapy is expected to improve survival of NSCLC. The aim of this study is to test the antiproliferative effect of pemetrexed combined with icotinib in different sequences on non-small cell lung cancer (NSCLC) cell lines to determine the optimal combination schedule, and subsequently elaborated the potential mechanisms.

Methods: Six human lung cancer cell lines with wild-type or mutant EGFR gene were exposed to pemetrexed and icotinib combined in different sequences. Cell proliferation was examined by cell counting kit-8 (CCK-8) and colony formation assay; cell cycle and apoptosis were evaluated by flow cytometry; cell migration and invasion were measured by wound healing and transwell invasion assays respectively; protein expression was by detected by Western blot.

Results: The growth inhibition effect of pemetrexed combined with icotinib on NSCLC cells were schedule-dependent in vitro and in vivo. Treatment with pemetrexed followed by icotinib (P-I) had significantly stronger anticancer ability than treatment with icotinib followed by pemetrexed (I-P) and concomitant treatment with pemetrexed and icotinib (P + I). Cell cycle analysis revealed that pemetrexed blocked cells in S phase, whereas icotinib arrested cells in G1 phase. We also found that icotinib markedly enhanced the pro-apoptotic activity of pemetrexed via cytochrome-C/Caspase/Bcl-2 signaling pathway. In addition, our results showed that pemetrexed alone increased the levels of p-EGFR, p-AKT and p-MAPK, which were inhibited by icotinib. Finally, we showed that the washout period of icotinib was no less than 96 h.

Conclusions: Sequential treatment of NSCLC cells with pemetrexed followed by icotinib had powerful antiproliferative effect, and it could become a novel effective combination therapy for NSCLC patients.
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http://dx.doi.org/10.1186/s13046-019-1133-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451286PMC
April 2019

Altered Plasma miR-144 as a Novel Biomarker for Coronary Artery Disease.

Ann Clin Lab Sci 2018 Jul;48(4):440-445

Department of Cardiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China

Background: MicroRNAs (miRNAs) have been found to be involved in coronary artery disease (CAD) and corresponding disease severity. The aim of this study is to determine plasma levels of miR-144 in CAD and its association with the severity of this disease.

Methods: Plasma levels of miR-144 in 60 CAD patients including stable angina pectoris (SAP) (n=29), unstable angina pectoris (UAP) or non-ST elevation myocardial infarction (MI) (NSTEMI) (n=17), or ST-elevation MI (STEMI) (n=14) and 20 non-CAD subjects were detected by real-time polymerase chain reaction (QRT-PCR). Associations of miR-144 expression with basic clinical characteristics and the severity of CAD were then analyzed.

Results: The QRT-PCR results showed that plasma miR-144 levels were increased in CAD patients, and among CAD patients, higher SYNTAX scores and STEMI were significantly associated with higher miR-144 expression.

Conclusions: Higher plasma levels of miR-144 were significantly associated with the presence as well as severity of CAD. As a potential biomarker for CAD, plasma miR-144 may be useful in predicting CAD and its severity.
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July 2018

Combination of Chymostatin and Aliskiren attenuates ER stress induced by lipid overload in kidney tubular cells.

Lipids Health Dis 2018 Jul 31;17(1):183. Epub 2018 Jul 31.

Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, 74# Zhongshan 2nd Road, Guangzhou, 510080, China.

Background: Lipotoxicity plays an important role in the pathogenesis of kidney injury. Our previous study demonstrated that activation of local renin-angiotensin system (RAS) was involved in saturated free fatty acids palmitic acid (PA)-induced tubular cell injuries. The current study aims to investigate whether suppression of RAS by combination of direct renin inhibitor aliskiren and noncanonical RAS pathway chymase inhibitor chymostatin attenuates PA or cholesterol induced-endoplasmic reticulum stress (ER stress) and apopotosis in cultured human proximal tubular HK2 cells.

Methods: HK2 cells were treated with saturated fatty acid PA (0.6 mM) for 24 h or cholesterol (10 μg/ml) for 6d with or without chymostatin and/or aliskiren. Expressions of the ER stress associated proteins and apoptosis markers were detected by western blotting. The mRNA levels of RAS components were measured by real-time qPCR.

Results: Combination treatment of chymostatin and aliskiren markedly suppressed PA or cholesterol-induced ER stress, as reflected by increased BiP, IRE1α, phosphorylated-eIF2α and ATF4 as well as proapoptotic transcription factor CHOP. The ratio of Bax/Bcl-2 and cleaved caspase-3, two markers of apoptosis were upregulated by PA or cholesterol treatment. PA treatment was also associated with increased levels of angiotensinogen and angiotensin type 1 receptor (AT1R) mRNA expression. Combination treatment of chymostatin and aliskiren markedly suppressed PA or cholesterol-induced ER stress and apoptosis. The protective effect of two inhibitors was also observed in primary cultured cortical tubular cells treated with PA. In contrast, chymostatin and/or aliskiren failed to prevent ER stress induced by tunicamycin.

Conclusions: These results suggested that combination treatment of chymostatin and aliskiren attenuates lipid-induced renal tubular cell injury, likely through suppressing activation of intracellular RAS.
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http://dx.doi.org/10.1186/s12944-018-0818-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069859PMC
July 2018

Combination exposure of melamine and cyanuric acid is associated with polyuria and activation of NLRP3 inflammasome in rats.

Am J Physiol Renal Physiol 2018 08 28;315(2):F199-F210. Epub 2018 Mar 28.

Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou , China.

The molecular mechanisms of melamine-induced renal toxicity have not been fully understood. The purpose of the study aimed to investigate whether melamine and cyanuric acid induced NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in the kidney, which may contribute to abnormal water and sodium handling in a rat model. Wistar rats received melamine (Mel; 200 mg·kg body wt·day), cyanuric acid (CA; 200 mg·kg body wt·day), or Mel plus CA (Mel + CA; 100 mg·kg body wt·day, each) for 2 wk. Mel + CA caused damaged tubular epithelial structure and organelles, dilated tubular lumen, and inflammatory responses. Crystals were observed in urine and serum specimen, also in the lumen of dilated distal renal tubules. The combined ingestion of Mel and CA in rats caused a markedly impaired urinary concentration, which was associated with reduced protein expression of aquaporin (AQP)1, 2, and 3 in inner medulla and α-Na-K-ATPase and Na-K-2Cl transporters in cortex and outer medulla. Mel + CA treatment was associated with increased protein expression of CD3 and mRNA levels of CD68 and F4/80 as well as phosphorylation of NF-κB in the kidney. Mel + CA treatment increased protein and mRNA expression of NLRP3 inflammasome components apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, and IL-1β in the inner medulla of rats. NF-κB inhibitor Bay 11-7082 reduced IL-1β expression induced by Mel + CA and prevented downregulation of AQP2 in inner medullary collecting duct cell suspensions. In conclusion, Mel + CA treatment caused urinary-concentrating defects and reduced expression of renal AQPs and key sodium transporters, which is likely due to the inflammatory responses and activation of NLRP3 inflammasome induced by crystals formed in the kidney.
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http://dx.doi.org/10.1152/ajprenal.00609.2017DOI Listing
August 2018

Association of beta-fibrinogen gene -148C/T and -455G/A polymorphisms and coronary artery disease in Chinese population: a meta analysis.

Sci China C Life Sci 2008 Sep 24;51(9):814-20. Epub 2008 Aug 24.

Department of Cardiology, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China.

The purpose of our study was to evaluate the correlation between the beta-fibrinogen gene -148C/T and -455G/A polymorphisms and susceptibility to coronary artery disease in the Chinese population using a meta-analytic approach. Eligible studies about this correlation were identified by searching the PubMed, EMBASE, and CNKI databases. Of the 13 identified, 7 (with 1488 cases and 1234 controls) involved the -148C/T polymorphism and 9 (with 1023 cases and 1081 controls) involved the -455G/A polymorphism. No publication bias was detectable and heterogeneity testing found significant differences between the ORs for both groups of studies. The combined OR for the 7 studies on susceptibility to coronary artery disease in -148T allele carriers compared to the -148C/C wild-type homozygotes was 1.31 (95%CI: 0.94-1.84, P = 0.11). The combined OR for the 9 studies on susceptibility to coronary artery disease in -455A allele carriers compared to the -455G/G wild-type homozygotes was 1.75 (95%CI: 1.24-2.46, P = 0.001). Our results suggest the absence of an association between the beta-fibrinogen gene -148C/T polymorphism and susceptibility to coronary artery disease and the possibility that -455G/A polymorphism (in particular, allele A) increases susceptibility to this disease in the Chinese population.
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http://dx.doi.org/10.1007/s11427-008-0102-0DOI Listing
September 2008