Publications by authors named "Yanxia Huang"

48 Publications

Novel compound heterozygous mutations in the gene cause macular corneal dystrophy in a Han Chinese family.

Ann Transl Med 2021 Apr;9(8):622

Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.

Background: Macular corneal dystrophy (MCD), a rare autosomal recessive disorder, is caused by pathogenic mutations in the carbohydrate sulfotransferase 6 gene () and is characterized by bilateral progressive stromal clouding and vision loss. Corneal transplantation is often necessary. This study aimed to identify disease-causing mutations in a Han-Chinese MCD patient.

Methods: A 37-year-old female diagnosed with MCD was recruited. The clinical materials were observed and described, and peripheral blood sample was extracted. Whole exome sequencing (WES) and Sanger sequencing were used to reveal genetic defects. The pathogenicity of identified mutations was assessed using analysis.

Results: The patient had typical features of MCD, including decreased vision, multiple irregular gray-white corneal opacities, and corneal thinning. A novel nonsense mutation c.544C>T (p.Gln182Ter) and a validated missense mutation c.631C>G (p.Arg211Gly) were identified in the gene coding region, both classified as "pathogenic" following the American College of Medical Genetics and Genomics standards and guidelines.

Conclusions: This study reports a Han-Chinese MCD patient with a novel nonsense mutation c.544C>T (p.Gln182Ter) and a recurrent missense mutation c.631C>G (p.Arg211Gly), which expand the spectrum of genetic mutations. The results of this study extend genotype-phenotype correlations between the gene mutations and MCD clinical findings, contributing to a more accurate diagnosis and the development of potential gene-targeted MCD therapies.

Keywords: Carbohydrate sulfotransferase 6 gene (); compound heterozygous mutations; Han Chinese family; macular corneal dystrophy (MCD).
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http://dx.doi.org/10.21037/atm-20-7178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106006PMC
April 2021

The Pharmacological Activity of the Wenjing Decoction in Recurrent Spontaneous Abortion.

Evid Based Complement Alternat Med 2021 13;2021:8861394. Epub 2021 Apr 13.

Department of Traditional Chinese Medicine, Sun Yat-sen Memorial Hospital, SunYat-sen University, Guangzhou 510120, Guangdong, China.

Background: Recurrent spontaneous abortion (RSA) is intractable infertility and can be ameliorated with the use of traditional Chinese medicine preparation, the Wenjing decoction. This study aimed to identify the therapeutic mechanism of Wenjing decoction on specific target proteins involved in RSA.

Methods: Wenjing decoction contains Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Ejiao, Mudanpi, Chishao, Dangshen, and Maidong. Using TCMSP and BATMAN databases, we queried for active ingredients and predicted their target proteins by BATMAN. Using the edgeR package, we analyzed the differentially expressed genes (DEGs) in the GSE121950 database between control samples and RSA ( = 3). The interaction between DEGs and the predicted target proteins was identified by the Venn diagram. Using the Cytoscape software and clusterProfiler package, enrichment analysis was conducted for the intersected target proteins. Additionally, the protein-protein interaction (PPI) network and pharmacological network were generated using the Cytoscape software.

Results: In total, 31, 2, 7, 7, 5, 13, 93, 11, 29, and 21 active ingredients were identified from Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Mudanpi, Chishao, and Dangshen, respectively. Additionally, 100 intersected target proteins were revealed by the Venn diagram. Moreover, 98 functional terms and 24 pathways (including C-type lectin receptor signaling pathway, chemokine signaling pathway, leukocyte transendothelial migration, fluid shear stress, and atherosclerosis, and AGE-RAGE signaling pathway in diabetic complications) were enriched. In the PPI network, 10 proteins involved in these five pathways were identified, namely, TNF- (tumor necrosis factor-), IL-10 (interleukin-10), TLR4 (Toll-like receptor 4), JUN (Jun proto-oncogene), IL-1B (interleukin-1-beta), CYBB (cytochrome b558 heavy chain gene), PTGS2 (prostaglandin-endoperoxide synthase 2), APOE (apolipoprotein E), SPI1 (salmonella pathogenicity island 1), and MPO (myeloperoxidase) which showed higher degrees.

Conclusion: The abovementioned genes and pathways might be involved in the pharmacological activity of Wenjing decoction in RSA.
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http://dx.doi.org/10.1155/2021/8861394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060116PMC
April 2021

Risk factors for secondary hemophagocytic lymphohistiocytosis in severe coronavirus disease 2019 adult patients.

BMC Infect Dis 2021 Apr 29;21(1):398. Epub 2021 Apr 29.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No 197, Rui Jin 2nd road, Shanghai, 200025, China.

Background: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors.

Method: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data.

Results: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 10/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19.

Conclusions: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.
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http://dx.doi.org/10.1186/s12879-021-06094-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084265PMC
April 2021

Emergence and Autochthonous Transmission of Dengue Virus Type I in a Low-Epidemic Region in Southeast China.

Front Cell Infect Microbiol 2021 24;11:638785. Epub 2021 Mar 24.

Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Background: Dengue fever is a mosquito-borne febrile illness. Southeast Asia experienced severe dengue outbreaks in 2019, and over 1000 cases had been reported in Jiangxi, a previously known low-epidemic region in China. However, the emergence of a dengue virus epidemic in a non-epidemic region remains unclear.

Methods: We enrolled 154 dengue fever patients from four hospitals in Jiangxi, from April 2019 to September 2019. Real-time PCR, NS1 antigen rapid test, and IgM, IgG tests were performed, and 14 samples were outsourced to be sequenced metagenomically.

Results: Among the 154 cases, 42 were identified as imported and most of them returned from Cambodia. A total of 113 blood samples were obtained and 106 were identified as DENV-1, two as DENV-2, and five were negative through RT-PCR. All DENV-1 strains sequenced in this study were all classified to one cluster and owned a high similarity with a Cambodia strain isolated in 2019. The evolutionary relationships of amino acid were consistent with that of nucleotide genome result. The sequence-based findings of Jiangxi strains were consistent with epidemiological investigation.

Conclusion: Epidemiological analysis demonstrated that the emergence of dengue cases led to autochthonous transmission in several cities in Jiangxi, a low-epidemic region before. This study emphasized future prevention and control of dengue fever in both epidemic and non-epidemic regions.
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http://dx.doi.org/10.3389/fcimb.2021.638785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024628PMC
March 2021

Guidelines for Regulated Cell Death Assays: A Systematic Summary, A Categorical Comparison, A Prospective.

Front Cell Dev Biol 2021 4;9:634690. Epub 2021 Mar 4.

Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China.

Over the past few years, the field of regulated cell death continues to expand and novel mechanisms that orchestrate multiple regulated cell death pathways are being unveiled. Meanwhile, researchers are focused on targeting these regulated pathways which are closely associated with various diseases for diagnosis, treatment, and prognosis. However, the complexity of the mechanisms and the difficulties of distinguishing among various regulated types of cell death make it harder to carry out the work and delay its progression. Here, we provide a systematic guideline for the fundamental detection and distinction of the major regulated cell death pathways following morphological, biochemical, and functional perspectives. Moreover, a comprehensive evaluation of different assay methods is critically reviewed, helping researchers to make a reliable selection from among the cell death assays. Also, we highlight the recent events that have demonstrated some novel regulated cell death processes, including newly reported biomarkers (e.g., non-coding RNA, exosomes, and proteins) and detection techniques.
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http://dx.doi.org/10.3389/fcell.2021.634690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970050PMC
March 2021

Positive Feedback Loop of Long Noncoding RNA OASL-IT1 and Innate Immune Response Restricts the Replication of Zika Virus in Epithelial A549 Cells.

J Innate Immun 2021 24;13(3):179-193. Epub 2021 Feb 24.

Key Laboratory of Tropical Disease Control, Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China,

Expression of host noncoding RNAs and coding mRNAs is significantly altered by viral infection. In the current study, we screened the transcriptional profile of human lung epithelial A549 cells infected with Zika virus (ZIKV) by microarray assay. Seventy-nine long noncoding RNAs (lncRNAs) and 140 mRNAs were differentially expressed (DE). The bioinformatics analysis revealed that the mRNAs adjacent to the DE lncRNAs were closely related to the host responses to viral infection. We selected 7 lncRNAs from the top 50 hits for validation. The quantitative real-time PCR data confirmed that expression of selected lncRNAs was induced by ZIKV infection. Moreover, the expression of 7 lncRNAs was induced by infection of dengue virus, Japanese encephalitis virus, or vesicular stomatitis virus, or by treatment of poly(I:C) and IFN-β. Furthermore, loss of innate immune adaptor IPS-1 or receptor IFNAR1 resulted in lower induction levels of several lncRNAs by ZIKV. Overexpression of 3 lncRNAs (RPL27-OT1, OASL-IT1, and REC8-OT3) reduced the virus yields of ZIKV. Knockout of OASL-IT1 significantly enhanced ZIKV replication. In OASL-IT1 knockout cells, the levels of interferons (IFNs) and the activation of 3 innate immune signaling pathways triggered by ZIKV were dramatically reduced. Collectively, our work found a positive feedback loop in the IFN system, in which IFNs and OASL-IT1 regulate each other, thereby promoting establishment of antiviral defense.
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http://dx.doi.org/10.1159/000513606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138224PMC
February 2021

c-FLIP regulates pyroptosis in retinal neurons following oxygen-glucose deprivation/recovery via a GSDMD-mediated pathway.

Ann Anat 2021 May 9;235:151672. Epub 2021 Jan 9.

Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, China. Electronic address:

Cellular FLICE-inhibitory protein (c-FLIP), an anti-apoptotic regulator, shows remarkable similarities to caspase-8, which plays a key role in the cleavage of gasdermin D (GSDMD). It has been reported that the oxygen-glucose deprivation/recovery (OGD/R) model and lipopolysaccharide (LPS)/adenosine triphosphate (ATP) treatment could induce inflammation and pyroptosis. However, the regulatory role of c-FLIP in the pyroptotic death of retinal neurons is unclear. In this study, we hypothesized that c-FLIP might regulate retinal neuronal pyroptosis by GSDMD cleavage. To investigate this hypothesis, we induced retinal neuronal damage in vitro (OGD/R and LPS/ATP) and in vivo (acute high intraocular pressure [aHIOP]). Our results demonstrated that the three injuries triggered the up-regulation of pyroptosis-related proteins, and c-FLIP could cleave GSDMD to generate a functional N-terminal (NT) domain of GSDMD, causing retinal neuronal pyroptosis. In addition, c-FLIP knockdown in vivo ameliorated the already established visual impairment mediated by acute IOP elevation. Taken together, these findings revealed that decreased c-FLIP expression protected against pyroptotic death of retinal neurons possibly by inhibiting GSDMD-NT generation. Therefore, c-FLIP might provide new insights into the pathogenesis of pyroptosis-related diseases and help to elucidate new therapeutic targets and potential treatment strategies.
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http://dx.doi.org/10.1016/j.aanat.2020.151672DOI Listing
May 2021

Exostosin1 as a novel prognostic and predictive biomarker for squamous cell lung carcinoma: A study based on bioinformatics analysis.

Cancer Med 2021 04 13;10(8):2787-2801. Epub 2020 Dec 13.

Guangdong Key Laboratory for Research and Development of Natural Drugs, Department of Pharmacology, Marine Medicine Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, China.

The exostosin (EXT) protein family is involved in diverse human diseases. However, the expression and prognostic value of EXT genes in human lung squamous cell carcinoma (LUSC) is not well understood. In this study, we analyzed the association between expression of EXT1 and EXT2 genes and survival in patients with LUSC using bioinformatics resources such as Oncomine and The Cancer Genome Atlas (TCGA) databases, the Gene Expression Profiling Interactive Analysis (GEPIA) server and Kaplan-Meier plotter. Furthermore, regulatory microRNAs (miRNAs) were predicted for EXT1 and used to establish a potential miRNA-messenger RNA (mRNA) regulation network for LUSC using the ENCORI platform. We observed that EXT1 and EXT2 expression levels were higher in LUSC than those in normal tissues. However, only EXT1 expression was significantly associated with poor overall survival (OS) in LUSC patients. Functional annotation enrichment analysis showed that genes co-expressed with the EXT1 gene were enriched in biological processes such as cell adhesion and migration, and KEGG pathways such as extracellular matrix receptor interactions, complement and coagulation cascades, and cell death. Furthermore, three miRNAs, hsa-mir-190a-5p, hsa-mir-195-5p, and hsa-mir-490-3p, were identified to be potentially involved in the regulation of EXT1. In summary, we identified EXT1 expression as a novel potential prognostic marker for human LUSC and the regulatory miRNAs that could possibly contribute to the prognosis of the disease.
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http://dx.doi.org/10.1002/cam4.3643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026939PMC
April 2021

Research on the Potential Mechanism of Gentiopicroside Against Gastric Cancer Based on Network Pharmacology.

Drug Des Devel Ther 2020 23;14:5109-5118. Epub 2020 Nov 23.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

Background: Gastric cancer was still one of the commonly diagnosed cancer types and the third-most common cause of cancer-related death in the world. Gentiopicroside, which is extracted from the , is commonly used in both traditional treatment and modern clinical care; therefore, its anticancer effects have been attracted more attention. However, the systematic analysis of action mechanism of Gentiopicroside on gastric cancer (GC) has not yet been carried out.

Aim: A network pharmacology-based strategy combined with molecular docking studies and in vitro validation was employed to investigate potential targets and molecular mechanism of Gentiopicroside against GC.

Materials And Methods: Potential targets of Gentiopicroside, as well as related genes of GC, were acquired from public databases. Potential targets, and signaling pathways were determined through bioinformatic analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the above findings.

Results: Our findings revealed that the anticancer activity of Gentiopicroside potentially involves 53 putative identified target genes. In addition, GO, KEGG, and network analyses revealed that these targets were associated with cell proliferation, metabolic process, and other physiological processes. Furthermore, we have proved that critical compound affected the expression of CCND1, CCNE1, p-AKT and p-P38 at protein levels. These findings provide an overview of the anticancer action of Gentiopicroside from a network perspective; meanwhile, it might also set an example for future studies of other materials used in traditional Chinese medicine (TCM).

Conclusion: This study comprehensively illuminated the potential targets and molecular mechanism of Gentiopicroside against GC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of TCM treating for disease.
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http://dx.doi.org/10.2147/DDDT.S270757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700081PMC
November 2020

Effects of sucrose on pasting, thermal, rheological and textural properties of native and alcohol-alkali-treated waxy rice starch.

Int J Biol Macromol 2021 Jan 21;166:108-116. Epub 2020 Oct 21.

College of Food Science, South China Agricultural University, Guangzhou, Guangdong 510642, China. Electronic address:

In this work, the physicochemical properties of native waxy rice starch (WRS) and alcohol-alkali-treated waxy rice starch (AAT-WRS) were studied in the presence of sucrose. The results indicated that the addition of sucrose improved the transparency and freeze-thaw stability of WRS pastes and AAT-WRS pastes. Differential scanning calorimetry showed that the gelatinization temperatures of WRS increased with increased sucrose concentration, but the gelatinization enthalpy increased at low concentration of sucrose and decreased at high concentration. Rheological measurements indicated that sucrose addition had no significant effect on the pseudoplastic shear-thinning behaviors of WRS pastes and AAT-WRS pastes, but changed the apparent viscosity. Dynamic moduli (G' and G″) values of WRS pastes and AAT-WRS pastes with or without sucrose showed frequency dependency and sucrose addition dependency. The elastic behavior was dominant over viscous in the WRS-sucrose mixed pastes, while the AAT-WRS-sucrose mixed pastes was the opposite. The textural paraments of WRS and AAT-WRS before or after retrogradation increased with the increasing concentration of sucrose. These results suggested that sucrose potentially changed the physicochemical properties of WRS and AAT-WRS.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.10.102DOI Listing
January 2021

Melatonin alleviates pyroptosis of retinal neurons following acute intraocular hypertension.

CNS Neurol Disord Drug Targets 2020 Oct 12. Epub 2020 Oct 12.

Department of Human Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan. China.

Background: Glaucoma is a multifactorial optic neuropathy progressive characterized by structural loss of retinal ganglion cells (RGCs) and irreversible loss of vision. High intraocular pressure (HIOP) is a high risk factor for glaucoma. It has been reported that the manners of RGCs' loss are in-depth explored after acute HIOP injury, such as, apoptosis, autophagy and necrosis. However, pyroptosis, a novel type of pro-inflammatory cell programmed necrosis, rarely reported after acute HIOP injury. Researches also showed that melatonin (MT) possesses substantial anti-inflammatory properties. However, whether melatonin could alleviate retinal neurons death, especially pyroptosis, by acute HIOP injury is unclear.

Objective: This study explored pyroptosis of retinal neurons and the effects of MT preventing retinal neurons form pyroptosis after acute HIOP injury.

Method: Establish acute HIOP model in rat by increasing the IOP and then reperfusion. Western Blot (WB) was adopted to detect molecules related to pyroptosis at the protein level, such as GasderminD (GSDMD), GasderminDp32 (GSDMDp32), Caspase-1 (Casp-1) and Caspase-1p20 (Casp-1p20), and the products of inflammatory reactions, as interleukin-18 (IL-18) and interleukin-1β (IL-1β) as well. At the same time, Immunofluorescence (IF) was used to co-localize Casp-1with retinal neurons to determine the position of Casp-1 expression. Morphologically, Ethidium homodimer-III staining, a method commonly used for judging cell death, was carried out to stain dead cells. Subsequently, Lactate Dehydrogenase (LDH) cytotoxicity assay kit was used to quantitative analysis the LDH released after cell disruption.

Results: The results suggested that pyroptosis played a vital role in retinal neurons death, especially in the ganglion cell layer, by acute HIOP injury and peaked at 6h after acute HIOP injury. Furthermore, it was found that MT might prevent retinal neurons from pyroptosis via NF-κB/NLRP3 axis after acute HIOP injury in rats.

Conclusion: MT treatment might be considered a new strategy for protecting retinal neurons against pyroptosis following acute HIOP injury.
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http://dx.doi.org/10.2174/1871527319666201012125149DOI Listing
October 2020

WITHDRAWN: Epidemiology and clinical analysis of the breakout of dengue fever in Zhangshu City, Jiangxi Province in 2019.

Med Mal Infect 2020 Oct 4. Epub 2020 Oct 4.

The Ninth Hospital of Nanchang, 330002 Nanchang, China. Electronic address:

This article has been withdrawn at the request of the author. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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http://dx.doi.org/10.1016/j.medmal.2020.09.017DOI Listing
October 2020

Inositol-Requiring Enzyme 1α Promotes Zika Virus Infection through Regulation of Stearoyl Coenzyme A Desaturase 1-Mediated Lipid Metabolism.

J Virol 2020 11 9;94(23). Epub 2020 Nov 9.

Key Laboratory of Tropical Diseases Control, Ministry of Education, Sun Yat-sen University, Guangzhou, China

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus which has become a global epidemic threat due to its rapid spread and association with serious consequences of infection, including neonatal microcephaly. Inositol-requiring enzyme 1α (IRE1α) is an endoplasmic reticulum (ER)-related transmembrane protein that mediates unfolded protein response (UPR) pathway and has been indicated to play an important role in flavivirus replication. However, the mechanism of how IRE1α affects ZIKV replication remains unknown. In this study, we explored the role of IRE1α in ZIKV infection and by using CRISPR/Cas9-based gene knockout and RNA interference-based gene knockdown techniques. Both knockout and knockdown of IRE1α dramatically reduced ZIKV replication levels, including viral RNA levels, protein expression, and titers in different human cell lines. -complementation with IRE1α restored viral replication levels decreased by IRE1α depletion. Furthermore, the proviral effect of IRE1α was dependent on its kinase and RNase activities. Importantly, we found that IRE1α promoted the replication of ZIKV through upregulating the accumulation of monounsaturated fatty acid (MUFA) rate-limiting enzyme stearoyl coenzyme A (stearoyl-CoA) desaturase 1 (SCD1), which further affected the production of oleic acid (OA) and lipid droplet. Finally, our data demonstrated that in the brain tissues of ZIKV-infected mice, the replication levels of ZIKV and virus-related lesions were significantly suppressed by both the kinase and RNase inhibitors of IRE1α. Taken together, our results identified IRE1α as a ZIKV dependency factor which promotes viral replication through affecting SCD1-mediated lipid metabolism, potentially providing a novel molecular target for the development of anti-ZIKV agents. Zika virus (ZIKV) has been linked to serious neurologic disorders and causes widespread concern in the field of global public health. Inositol requiring enzyme 1α (IRE1α) is an ER-related transmembrane protein that mediates unfolded protein response (UPR) pathway. Here, we revealed that IRE1α is a proviral factor for ZIKV replication both in culture cells and mice model, which relies on its kinase and RNase activities. Importantly, we further provided evidence that upon ZIKV infection, IRE1α is activated and splices mRNA which enhances the expression of monounsaturated fatty acids rate-limiting enzyme stearoyl coenzyme A (stearoyl-CoA) desaturase 1 (SCD1) and subsequent lipid droplet production. Our data uncover a novel mechanism of IRE1α proviral effect by modulating lipid metabolism, providing the first evidence of a close relationship between IRE1α-mediated UPR, lipid metabolism, and ZIKV replication and indicating IRE1α inhibitors as potentially effective anti-ZIKV agents.
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http://dx.doi.org/10.1128/JVI.01229-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654271PMC
November 2020

Epidemiological and clinical analysis of the outbreak of dengue fever in Zhangshu City, Jiangxi Province, in 2019.

Eur J Clin Microbiol Infect Dis 2021 Jan 14;40(1):103-110. Epub 2020 Aug 14.

The Ninth Hospital of Nanchang, No. 167 Hongdu Central Road, Nanchang, 330002, China.

This study analyzed the epidemiological and clinical features of dengue fever in Zhangshu, Jiangxi Province, in 2019 and provided evidence for the diagnosis, treatment, prevention, and control of dengue fever. A total of 718 dengue fever patients in Zhangshu in 2019 were involved. ELISA and qRT-PCR were used for pathogenic detection of dengue virus. Multiple adjuvant therapies were applied, and the condition of patients after treatment was examined. Patients were between the ages of 0.75 and 92 years old, and all of them had a fever. A total of 519 cases had fatigue, and 413 cases had generalized myalgia and bone ache; 356 cases had dry mouth, 289 cases had bitter taste, and 167 cases felt dry and bitter taste; 279 cases had rash, and 93 cases had pruritus; 587 cases had decreased leukocyte, among which, 7 cases had leukocyte lower than 1 × 10 [9]/L; 380 cases had a low platelet count, and the platelet count of 29 cases was lower than 50 × 10 [9]/L; 488 cases had increased aspartic transaminase, and 460 cases had increased alanine aminotransferase; 5 cases had a severe disease. It proved that the majority of dengue fever sufferers were adults, with the main clinical features being fever and rash and the chief injured organs being the blood system, liver, heart, and gastrointestinal tract. Besides, over 40% of patients had dry and bitter taste, and 12 cases had alopecia after discharge. It indicates that the incidence of dengue fever in Zhangshu is closely related to the sudden population flow and imported cases.
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http://dx.doi.org/10.1007/s10096-020-03962-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426594PMC
January 2021

ANKS4B Restricts Replication of Zika Virus by Downregulating the Autophagy.

Front Microbiol 2020 22;11:1745. Epub 2020 Jul 22.

Key Laboratory of Tropical Disease Control, Zhongshan School of Medicine, Sun Yat-sen University, Ministry of Education, Guangzhou, China.

Infection of Zika virus (ZIKV) has become a severe threaten to global health while no specific drug is available. In this study, we explored the relationship between ZIKV and a cellular protein, ankyrin repeat and sterile motif domain containing 4b (ANKS4B). Our data revealed that the expression of in cultured cells and in neonatal mice was downregulated by ZIKV infection. The reduction of upon ZIKV infection was caused by decrease of two hepatocyte nuclear factors and . Through CRISPR/Cas9 gene editing system, we generated two ANKS4B knockout (KO) cell clones in A549 and Huh7 cells respectively. In the ANKS4B-KO cells, the viral replication levels including viral RNA, protein, and titer were significantly enhanced, which was reversed by -complementation of ANKS4B. ANKS4B did not affect the viral entry step, but impaired the autophagy induced by ZIKV infection. Furthermore, our data showed that inhibition of autophagy led to similar replication levels of ZIKV in ANKS4B-sufficient and ANKS4B-deficient cells, suggesting the antiviral effect of ANKS4B relied on its modulation on the autophagy. Therefore, our work identified ANKS4B as a new restriction factor of ZIKV.
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http://dx.doi.org/10.3389/fmicb.2020.01745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387654PMC
July 2020

Correction to: LncRNA AK023391 promotes tumorigenesis and invasion of gastric cancer through activation of the PI3K/Akt signaling pathway.

J Exp Clin Cancer Res 2020 08 12;39(1):155. Epub 2020 Aug 12.

Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s13046-020-01656-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422566PMC
August 2020

Increased levels of conjugated bile acids are associated with human bile reflux gastritis.

Sci Rep 2020 07 14;10(1):11601. Epub 2020 Jul 14.

Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Bile acids (BAs) play essential roles in facilitating lipid digestion and absorption in the intestine. Gastric BAs were attributed to abnormal refluxing from duodenal compartments and correlated with the occurrence of gastric inflammation and carcinogenesis. However, the differences in gastric BAs between physiologically compromised and healthy individuals have not been fully investigated. In this study, gastric juice was collected from patients clinically diagnosed as gastritis with/without bile reflux and healthy subjects for BA profiles measurements. As a result, we found that the conjugated BAs became prominent components in bile reflux juice, whereas almost equal amounts of conjugated and unconjugated BAs existed in non-bile reflux and healthy juice. To investigate whether gastric BA changes were regulated by hepatic BA synthesis, C57BL/6J mice were intervened with GW4064/resin to decrease/increase hepatic BA synthesis. The results revealed that changes of gastric BAs were coordinated with hepatic BA changes. Additionally, gastric BAs were detected in several healthy mammals, in which there were no obvious differences between the conjugated and unconjugated BAs. Pigs were an exception. Thus, increased levels of conjugated BAs are associated with human bile reflux gastritis. Gastric conjugated BAs could become a panel of biomarkers to facilitate diagnosis of pathological bile reflux.
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http://dx.doi.org/10.1038/s41598-020-68393-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360626PMC
July 2020

Downregulation of MST4 Underlies a Novel Inhibitory Role of MicroRNA Let-7a in the Progression of Retinoblastoma.

Invest Ophthalmol Vis Sci 2020 06;61(6):28

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Purpose: Retinoblastoma (RB) is the most common intraocular malignancy in children. Deregulation of several microRNAs (miRNAs) has been identified in RB. However, the specific effect of let-7a on RB remains unclear. The present study aims to explore the effect of let-7a on malignant biological behaviors of RB cells and angiogenesis in RB.

Methods: The expressions of let-7a and mammalian sterile-20 like kinase 4 (MST4) in RB were determined with the use of real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Next, in order to explore effects of let-7a and MST4 on RB cellular functions, RB cells were transfected with let-7a-mimic, let-7a inhibitor, si-MST4, or co-transfected with let-7a-mimic and oe-MST4 plasmids. Subsequently, the interaction among let-7a, MST4, and the MAPK signaling pathway was evaluated by RT-qPCR, dual-luciferase reporter gene assay, and Western blot analysis. Finally, the effects of let-7a and MST4 were further confirmed in vivo by injecting nude mice with RB cells stably expressing let-7a agomir or sh-MST4.

Results: Rb tissues and cells presented with downregulated Let-7a and upregulated MST4. Let-7a negatively targeted MST4 to block the activation of the MAPK signaling pathway. Upregulation of let-7a promoted apoptosis, and facilitated proliferation, angiogenesis, migration, and invasion of RB cells by decreasing MST4. Elevation of let-7a or silencing MST4 restricted angiogenesis and tumorigenesis in RB mice.

Conclusions: Taken together, let-7a inhibits angiogenesis in RB by silencing MST4 and inhibiting the MAPK signaling pathway.
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http://dx.doi.org/10.1167/iovs.61.6.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415300PMC
June 2020

A comparative study on the time to achieve negative nucleic acid testing and hospital stays between danoprevir and lopinavir/ritonavir in the treatment of patients with COVID-19.

J Med Virol 2020 11 24;92(11):2631-2636. Epub 2020 Jun 24.

The First Department of Infectious Disease, The Ninth Hospital of Nanchang, Nanchang, Jiangxi, China.

In late December 2019, coronavirus disease 2019 (COVID-19) first broke out in Wuhan, China, and has now become a global pandemic. However, there is no specific antiviral treatment for COVID-19. This study enrolled 33 COVID-19 patients in the nineth hospital of Nanchang from 27th January to 24th February 2020. Clinical indexes of patients upon admission/discharge were examined. Patients were divided into two groups according to different treatment plans (danoprevir and lopinavir/ritonavir). The days to achieve negative nucleic acid testing and the days of hospital stays were counted and statistically analyzed. COVID-19 patients treated with danoprevir or lopinavir/ritonavir were all improved and discharged. Indexes like blood routine, inflammation and immune-related indexes were significantly recovered after treatment. Additionally, under the circumstance that there was no significant difference in patients' general information between the two groups, we found that the mean time to achieve both negative nucleic acid testing and hospital stays of patients treated with danoprevir were significantly shorter than those of patients with lopinavir/ritonavir. Collectively, applying danoprevir is a good treatment plan for COVID-19 patients.
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http://dx.doi.org/10.1002/jmv.26141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300667PMC
November 2020

Downregulation of microRNA-224-3p Hampers Retinoblastoma Progression via Activation of the Hippo-YAP Signaling Pathway by Increasing LATS2.

Invest Ophthalmol Vis Sci 2020 03;61(3):32

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Purpose: The pivotal role of microRNAs (miRNAs or miRs) has been proved in the pathogenesis of retinoblastoma. miR-224-3p is demonstrated to be involved in several tumors. However, the underlying mechanism of miR-224-3p in retinoblastoma is yet to be investigated. Therefore, this study was designed to identify the regulation of miR-224-3p in human retinoblastoma.

Methods: The expression pattern of miR-224-3p and large tumor suppressor 2 (LATS2) in retinoblastoma was measured by reverse transcription quantitative polymerase chain reaction. Afterward, the interaction between miR-224-3p and LATS2 was identified using a dual luciferase reporter gene assay. Next, gain-of-function and loss-of-function approaches were employed to examine the effects of miR-224-3p and LATS2 as well as their interaction on cell apoptosis, proliferation and angiogenesis abilities, and tumorigenesis. Whether the Hippo-YAP signaling pathway was involved in tumorigenesis was analyzed by determining downstream genes.

Results: LATS2 was downregulated in retinoblastoma, and its overexpression promoted apoptosis and suppressed proliferation of retinoblastoma cells. miR-224-3p, highly expressed in retinoblastoma, inhibited the expression of its target gene LATS2, which inhibited activation of the Hippo-YAP signaling pathway. Suppression of miR-224-3p promoted apoptosis while suppressing the proliferation of retinoblastoma cells and angiogenesis. Tumor progression induced by upregulation of miR-224-3p was diminished by restoration of LATS2. It was observed that tumor growth and angiogenesis were reduced by depleted miR-224-3p in the animal experiments.

Conclusions: The present study suggests that miR-224-3p targets LATS2 and blocks the Hippo-YAP signaling pathway activation, thus preventing the progression of retinoblastoma, which could be a new therapeutic target for retinoblastoma.
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http://dx.doi.org/10.1167/iovs.61.3.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401717PMC
March 2020

RSK3 mediates necroptosis by regulating phosphorylation of RIP3 in rat retinal ganglion cells.

J Anat 2020 07 12;237(1):29-47. Epub 2020 Mar 12.

Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, China.

Receptor-interacting protein 3 (RIP3) plays an important role in the necroptosis signaling pathway. Our previous studies have shown that the RIP3/mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis occurs in retinal ganglion cell line 5 (RGC-5) following oxygen-glucose deprivation (OGD). However, upstream regulatory pathways of RIP3 are yet to be uncovered. The purpose of the present study was to investigate the role of p90 ribosomal protein S6 kinase 3 (RSK3) in the phosphorylation of RIP3 in RGC-5 cell necroptosis following OGD. Our results showed that expression of RSK3, RIP3, and MLKL was upregulated in necroptosis of RGC-5 after OGD. A computer simulation based on our preliminary results indicated that RSK3 might interact with RIP3, which was subsequently confirmed by co-immunoprecipitation. Further, we found that the application of a specific RSK inhibitor, LJH685, or rsk3 small interfering RNA (siRNA), downregulated the phosphorylation of RIP3. However, the overexpression of rip3 did not affect the expression of RSK3, thereby indicating that RSK3 could be a possible upstream regulator of RIP3 phosphorylation in OGD-induced necroptosis of RGC-5 cells. Moreover, our in vivo results showed that pretreatment with LJH685 before acute high intraocular pressure episodes could reduce the necroptosis of retinal neurons and improve recovery of impaired visual function. Taken together, our findings suggested that RSK3 might work as an upstream regulator of RIP3 phosphorylation during RGC-5 necroptosis.
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http://dx.doi.org/10.1111/joa.13185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309291PMC
July 2020

Zika virus-spread, epidemiology, genome, transmission cycle, clinical manifestation, associated challenges, vaccine and antiviral drug development.

Virology 2020 04 2;543:34-42. Epub 2020 Feb 2.

Department of Cell Biology, School of Life Sciences, Central South University, Changsha, 410013, China; Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410013, China. Electronic address:

Zika Virus (ZIKV) is a Flavivirus transmitted primarily via the bite of infected Aedes aegypti mosquitoes. Globally, 87 countries and territories have recorded autochthonous mosquito-borne transmission of ZIKV as at July 2019 and distributed across four of the six WHO Regions. Outbreaks of ZIKV infection peaked in 2016 and declined substantially throughout 2017 and 2018 in the Americas region. There is the likely risk for ZIKV to spread to more countries. There is also the potential for the re-emergence of ZIKV in all places with prior reports of the virus transmission. The current status of ZIKV transmission and spread is, however, a global health threat, and from the aforementioned, has the potential to re-emerge as an epidemic. This review summarizes the past and present spread of ZIKV outbreak-2007-2019, the genome, transmission cycle, clinical manifestations, vaccine and antiviral drug advancement.
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http://dx.doi.org/10.1016/j.virol.2020.01.015DOI Listing
April 2020

Hydroxycarboxylic Acid Receptor 2 Is a Zika Virus Restriction Factor That Can Be Induced by Zika Virus Infection Through the IRE1-XBP1 Pathway.

Front Cell Infect Microbiol 2019 22;9:480. Epub 2020 Jan 22.

Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Zika virus (ZIKV) is an emerging arthropod-borne virus and belongs to the family. The infection of ZIKV has become the global health crisis because of its rapid spread and association with severe neurological disorders, including congenital microcephaly and Guillain-Barre Syndrome. To identify host factors contributing to ZIKV pathogenesis, transcriptomic landscape in ZIKV-infected cells was examined with mRNA microarray analysis and we observed that the expression of hydroxycarboxylic acid receptor 2 (HCAR2) could be significantly induced by ZIKV infection. By utilizing two IRE1 inhibitors and -specific shRNAs, we revealed that the up-regulation of HCAR2 expression induced by ZIKV was dependent on the IRE1-XBP1 pathway. Through the CRISPR/Cas9 system, we generated HCAR2-deficient cell clones in two cell types (human lung carcinoma epithelial A549 cell and human hepatoma Huh7.5 cell). We found that the depletion of HCAR2 significantly increased the replication level of ZIKV, including RNA levels, protein expression levels, and viral titers. In addition, our data demonstrated that the antiviral effect of HCAR2 was not involved in viral entry process and was not dependent on its antilipolytic effect on nicotinic acid/HCAR2-mediated signaling pathway. Taken together, our results indicated that HCAR2 could function as a restriction factor in control of ZIKV replication, potentially providing a novel molecular target for anti-ZIKV therapeutics.
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http://dx.doi.org/10.3389/fcimb.2019.00480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990111PMC
August 2020

The Correlation Between Fall Prevention Knowledge and Behavior in Stroke Outpatients.

J Neurosci Nurs 2020 Apr;52(2):61-65

Background: Stroke outpatients have a high risk of falling. However, fall prevention measures in the community are insufficient to effectively reduce the fall rate among outpatients with stroke. We aimed to determine the correlation between fall prevention knowledge and behavior among outpatients with stroke and provide new strategies for community fall prevention.

Methods: We recruited 124 patients with stroke who were followed up in the outpatient department of a tertiary hospital in Zhuhai, China. Patients were assessed using a general information questionnaire, a fall prevention knowledge questionnaire for patients with stroke, and the Stroke Fall Prevention Behavior Scale. IBM SPSS 22.0 software was used for statistical analysis.

Results: The median fall prevention knowledge was 82.76 (68.97, 93.10) points, out of 100. The mean (SD) score for fall prevention behavior was 2.90 (0.52; range, 1-4) points. Fall prevention knowledge scores were positively related to those fall prevention behavior (Spearman r = 0.454, P < .01).

Conclusion: Levels of fall prevention knowledge among outpatients with stroke were adequate, and this population had medium to high levels of fall prevention behavior. Better knowledge was accompanied with better prevention of falls. However, whether enriching the knowledge could lead to improvement of fall prevention is still undetermined.
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http://dx.doi.org/10.1097/JNN.0000000000000494DOI Listing
April 2020

Double-stranded RNA deaminase ADAR1 promotes the Zika virus replication by inhibiting the activation of protein kinase PKR.

J Biol Chem 2019 11 21;294(48):18168-18180. Epub 2019 Oct 21.

Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Zika virus (ZIKV) is a mosquito-borne flavivirus that has emerged as a threat to global health. The family of adenosine deaminases acting on dsRNA (ADARs) are human host factors important for the genetic diversity and evolution of ZIKV. Here, we further investigated the role of ADAR1 in ZIKV replication by utilizing CRISPR/Cas9-based gene editing and RNAi-based gene knockdown techniques. Both ADAR1 knockout and knockdown significantly reduced ZIKV RNA synthesis, protein levels, and viral titers in several human cell lines. -complementation with the full-length ADAR1 form p150 or the shorter form p110 lacking the Zα domain restored viral replication levels suppressed by the ADAR1 knockout. Moreover, we observed that the nuclear p110 form was redistributed to the cytoplasm in response to ZIKV infection. ADAR1 was not involved in viral entry but promoted viral protein translation by impairing ZIKV-induced activation of protein kinase regulated by dsRNA (PKR). Of note, the RNA-editing activity of ADAR1 was not required to promote ZIKV replication. We also found that the proviral role of ADAR1 was partially mediated through its ability to suppress IFN production and PKR activation. Our work identifies ADAR1 as a proviral factor involved in ZIKV replication, suggesting that ADAR1 could be a potential antiviral target.
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http://dx.doi.org/10.1074/jbc.RA119.009113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885634PMC
November 2019

A sustainable process for the recovery of volatile constituents from in agar production and evaluation of their antioxidant activities.

BMC Chem 2019 Dec 31;13(1):74. Epub 2019 May 31.

2Affiliated Hospital, Guangdong Medical University, Zhanjiang, 524023 China.

Background: is a common red alga used as a raw material source for the agar industry. Its extract is rich in natural volatile constituents (VCs) having antioxidant activities. Herein, a sustainable method was used to recover VCs from the alga. The chemical composition of VCs present in the -hexane fraction was analyzed by gas chromatography-mass spectroscopy (GC-MS) and the antioxidant potential was measured using a series of in vitro biochemical assays, including DPPH, hydroxyl, and superoxide radical scavenging assays.

Results: The recovery yield of the VCs was 0.823 wt% of the dry mass of . A total of 25 VCs were successfully identified, comprising approximately 99.94% of the total volume. The major component was -hexadecanoic acid (38.57%), followed by oleic acid (25.48%), arachidonic acid (12.84%), and tetradecanoic acid (2.52%). In addition, The VCs displayed strong free radical scavenging activity in the DPPH (IC = 21.56 mg/L), hydroxyl (IC = 18.34 mg/L), and superoxide (IC = 391.12 mg/L) radical scavenging assays. The antioxidant activities of the VCs exhibited a dose-dependence at concentrations ranging from 5 to 200 mg/L.

Conclusion: The results indicated that the sustainable process improved the agar quality and that the extract contained many natural VCs with antioxidant activities, which have the potential to be used in functional food and cosmetics instead of as a discarded byproduct of the agar industry.
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http://dx.doi.org/10.1186/s13065-019-0590-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661735PMC
December 2019

Pin1 Is Regulated by CaMKII Activation in Glutamate-Induced Retinal Neuronal Regulated Necrosis.

Front Cell Neurosci 2019 25;13:276. Epub 2019 Jun 25.

Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China.

In our previous study, we reported that peptidyl-prolyl isomerase 1 (Pin1)-modulated regulated necrosis (RN) occurred in cultured retinal neurons after glutamate injury. In the current study, we investigated the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in Pin1-modulated RN in cultured rat retinal neurons, and in an animal model. We first demonstrated that glutamate might lead to calcium overloading mainly through ionotropic glutamate receptors activation. Furthermore, CaMKII activation induced by overloaded calcium leads to Pin1 activation and subsequent RN. Inactivation of CaMKII by KN-93 (KN, i.e., a specific CaMKII inhibitor) application can decrease the glutamate-induced retinal neuronal RN. Finally, by using an animal model, we also demonstrated the important role of CaMKII in glutamate-induced RN in rat retina. In addition, flash electroretinogram results provided evidence that the impaired visual function induced by glutamate can recover after CaMKII inhibition. In conclusion, CaMKII is an up-regulator of Pin1 and responsible for the RN induced by glutamate. This study provides further understanding of the regulatory pathway of RN and is a complementary mechanism for Pin1 activation mediated necrosis. This finding will provide a potential target to protect neurons from necrosis in neurodegenerative diseases, such as glaucoma, diabetic retinopathy, and even central nervous system diseases.
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http://dx.doi.org/10.3389/fncel.2019.00276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603237PMC
June 2019

Correction to: Circular RNA YAP1 inhibits the proliferation and invasion of gastric cancer cells by regulating the miR-367-5p/p27 Kip1 axis.

Mol Cancer 2019 Jul 9;18(1):117. Epub 2019 Jul 9.

Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China.

After the publication of this work [1], a spelling error was found: the ID of the circRNA, termed circYAP1, in the original publication was misspelled as "has_circ_0002320".
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http://dx.doi.org/10.1186/s12943-019-1045-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615290PMC
July 2019

Connectivity map identifies luteolin as a treatment option of ischemic stroke by inhibiting MMP9 and activation of the PI3K/Akt signaling pathway.

Exp Mol Med 2019 03 25;51(3):1-11. Epub 2019 Mar 25.

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

This study aimed to explore potential new drugs in the treatment of ischemic stroke by Connectivity Map (CMap) and to determine the role of luteolin on ischemic stroke according to its effects on matrix metalloproteinase-9 (MMP9) and PI3K/Akt signaling pathway. Based on published gene expression data, differentially expressed genes were obtained by microarray analysis. Potential compounds for ischemic stroke therapy were obtained by CMap analysis. Cytoscape and gene set enrichment analysis (GSEA) were used to discover signaling pathways connected to ischemic stroke. Cell apoptosis and viability were, respectively, evaluated by flow cytometry and an MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were used to test the expression of MMP9 and the PI3K/Akt signaling pathway-related proteins in human brain microvascular endothelial cells (HBMECs) and tissues. Additionally, the infarct volume after middle cerebral artery occlusion (MCAO) was determined by a TTC (2,3,5-triphenyltetrazolium chloride) assay. The microarray and CMap analyses identified luteolin as a promising compound for future therapies for ischemic stroke. Cytoscape and GSEA showed that the PI3K/Akt signaling pathway was crucial in ischemic stroke. Cell experiments revealed that luteolin enhanced cell viability and downregulated apoptosis via inhibiting MMP9 and activating the PI3K/Akt signaling pathway. Experiments performed in vivo also demonstrated that luteolin reduced the infarct volume. These results suggest that luteolin has potential in the treatment of ischemic stroke through inhibiting MMP9 and activating PI3K/Akt signaling pathway.
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http://dx.doi.org/10.1038/s12276-019-0229-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434019PMC
March 2019

Wide-range precision temperature measurement with optomechanically induced transparency in a double-cavity optomechanical system.

Opt Express 2019 Feb;27(3):2949-2961

This paper proposes a scheme for wide-range precision measurement of the environmental temperature in a double-cavity optomechanical system. This system consists of an optomechanical cavity coupling to the other cavity via photon tunneling interaction. Bycontrolling the tunnelling strength between the two cavities, double optomechanically induced transparency (double OMIT) effect is observed in the homodyne spetra of the outfield. It is shown that the central peak value depends linearly on the environmental temperature. Based on this linear relationship, the environmental temperature can be inferred from the central peak value of the output homodyne spectrum. This scheme is robust against mechanical decay and it shows high sensivity over a wide temperature range.
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http://dx.doi.org/10.1364/OE.27.002949DOI Listing
February 2019