Circular RNAs are involved in the pathogenesis of osteoarthritis through intracellular mechanisms / 中国组织工程研究

BACKGROUND:Currently,there is no drug that can completely cure osteoarthritis and its pathogenesis is still unclear.Circular RNAs(circRNAs)are differentially expressed in patients with osteoarthritis and are closely associated with various pathological processes in osteoarthritis.circRNAs play an important role in various physiological and pathological processes,such as chondrocyte homeostasis,extracellular matrix formation,and inflammatory response. OBJECTIVE:To mainly review the effects of circRNAs on pathological factors related to osteoarthritis,as well as the types and expression levels of circRNAs in osteoarthritis. METHODS:Related articles published from 1976 to August 2023 were retrieved from CNKI,WanFang,VIP,PubMed,Medline,Web of Science and Elsevier databases.The keywords were"osteoarthritis,circular RNA,non-coding RNA,synovial tissue,chondrocytes"in Chinese and English,respectively.All the relevant articles were screened,summarized,analyzed,and finally 69 papers were included in the review. RESULTS AND CONCLUSION:circRNAs are non-coding RNAs widely found in eukaryotic cells,with covalently closed continuous loop structure,but with no 5'hat structure and 3'poly A tail,which are involved in multi-gene and multi-target regulatory networks and cannot be degraded by nucleic acid exonucleases(RNase R).circRNAs have a high abundance,high conservativeness and stability,and cell and tissue specificity.circRNAs have biological functions such as acting as molecular sponges for miRNAs,regulating linear RNA transcription and RNA shearing,interacting with RNA-bound proteins,and translating proteins.circRNAs regulate chondrocyte apoptosis and proliferation,degradation of cartilage extracellular matrix,and inflammation and other physiopathologic processes.circRNAs are expected to become biomarkers and potential therapeutic targets for clinical diagnosis and prognosis of osteoarthritis,and may become a new strategy for clinical treatment of osteoarthritis in the future.

Effect of interfering hsa_circ_0103232 on the biological behavior of uveal melanoma cells / 中华实验眼科杂志

Objective:To investigate the effects of interference with hsa_circ_0103232 on the proliferation, metastasis, cell cycle and apoptosis of melanoma cells C918 and MUM2B.Methods:C918 and MUM2B cells were cultured, and the interference efficiency of three small interfering RNA (siRNA) targeting hsa_circ_0103232 were detected by real-time fluorescent quantitative polymerase chain reaction (PCR).The siRNA with the highest interference efficiency was used for the following experiment.Both C918 and MUM2B cells were divided into negative control transfection (siCtrl) groups and interference (si-hsa_circ_0103232) groups.The proliferation of C918 and MUM2B cells was examined by cell counting kit-8 (CCK-8) assay and cell colony formation assay.The migration of C918 and MUM2B cells was determined by transwell assay.The cell cycle distribution and apoptosis rate of C918 and MUM2B cells were detected by flow cytometry.The localization of hsa_circ_0103232 in C918 and MUM2B cells was tested by the fluorescence in situ hybridization experiment (FISH).Results:The results of real-time quantitative PCR showed that among the three siRNAs targeting hsa_circ_0103232, si-hsa_circ_0103232#1 had the best effect, which reduced the expression level of gene in C918 and MUM2B cells to 0.263±0.016 and 0.469±0.028, significanthy lower than 1.013±0.008 and 1.004±0.108 of control groups (both at P<0.001).CCK-8 results showed that the proliferation activity of C918 and MUM2B cells was significantly lower in si-hsa_circ_0103232 group than in siCtrl group after transfection (all at P<0.05).The results of cell clone formation showed that the clone number of C918 and MUM2B cells in si-hsa_circ_0103232 group were 12±1 and 45±7, which were significantly lower than 28±4 and 83±3 in siCtrl group, and the differences were statistically significant ( t=4.93, 7.42; both at P<0.05).Transwell assay results showed that the number of migrating C918 and UM2B cells in si-hsa_circ_0103232 group were 4±1 and 24±2, respectively, which were significantly lower than 37±12 and 57±3 in siCtrl group, and the differences were statistically significant ( t=3.91, 10.80; both at P<0.05).The results of flow cytometry showed that compared with siCtrl group, the proportion of G1 phase cells in C918 and MUM2B cells in si-hsa_circ_0103232 group increased significantly, the proportion of G2/M phase cells decreased significantly, and the number of apoptotic cells increased significantly (all at P<0.05).FISH experiment showed that hsa_circ_0103232 was located in the nuclei of C918 and MUM2B cells. Conclusions:Interference with hsa_circ_0103232 can inhibit the proliferation, migration and cycle progression of C918 and MUM2B cells, and promote their apoptosis.hsa_circ_0103232 may be a new therapeutic target for uveal melanoma.

Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

Research progress on role and mechanism of PA28γ in immune-related diseases / 中国免疫学杂志

Proteasome activator PA28γ,also known as Ki antigen,REGγ or PSME3,is first found as Ki antigen in the serum of a patient with systemic lupus erythematosus,which belongs to 11S proteasome activator family together with PA28α and PA28β.In the amino acid sequence,PA28γ has 25%homology with PA28α and PA28β and its seven-subunit homomer is a 20S proteasome acti-vator,which mainly exists in the nucleus and participates in ubiquitin and ATP-dependent or independent protein degradation.More and more studies have reported the role of PA28γ in human immune-related diseases.This article reviews the function of PA28γ as a proteasome activator and its role in immune-related diseases including cancer,inflammation and virus infection-related diseases and other diseases in recent years,so as to reveal the role of PA28γ in the occurrence and development of immune-related diseases and its potential as a target for immunotherapy.

Research Progress of Long Non-Coding RNA in Hematological Tumors --Review / 中国实验血液学杂志

Long non-coding RNA (lncRNA) is a hot topic in the field of researching tumor pathogenesis, and the importance in hematologic malignancies has been gradually being elucidated. LncRNA not only regulates hematological tumorigenesis and progression through affecting various biological processes such as cell proliferation, differentiation, pluripotency and apoptosis; moreover, abnormal expression and mutation of lncRNA are closely related to drug resistance and prognosis. Thus lncRNA can be used as novel biomarker and potential therapeutic target for hematological tumors. In this review, we will focus on the latest progress of lncRNA in hematological tumors to provide new ideas for the clinical diagnosis, prognostic evaluation together with research and development of target drugs for hematologic malignancies.

Research Progress of Pseudogenes in Hepatocellular Carcinoma / 肿瘤防治研究

Pseudogenes were initially thought to have no function and were called by aliases, such as "junk genes." With the emergence of large-scale genomics projects and more and more experimental studies, pseudogenes have been shown to play an important role in the occurrence and development of solid tumors, especially playing an important regulatory role in the occurrence and develepment of liver cancer, such as regulating the proliferation, apoptosis, invasion, metastasis, and immunity of liver cancer cells. Recent studies showed that pseudogenes can act as regulators of oncogenes and tumor suppressors in hepatocellular carcinoma (HCC) and can thus serve as prognostic markers and even therapeutic targets for this cancer type. In this review, we systematically summarize the mechanisms and functions of different pseudogenes in HCC and present their future prospects as therapeutic targets.

Bioinformatic analysis of the expression of KIF14 and its clinical significance and biological functions in clear cell renal cell carcinoma / 现代泌尿外科杂志

【Objective】 To investigate the expression of Kinesin family member 14 (KIF14), and its correlation with clinical prognosis and immune cell infiltration of clear cell renal cell carcinoma (ccRCC). 【Methods】 The correlation between KIF14 expression in ccRCC and different clinicopathological features were analyzed with TCGA, GEO and Ualcan databases. The correlation between KIF14 expression and prognosis was analzyed with Kaplan-Meier method. The correlation between KIF14 expression and immune cell infiltration was analzyed with TIMER. The protein-protein interaction network of KIF14 was conducted with Genemania. The co-expression genes of KIF14 in TCGA-KIRC were picked out in Linkedomics database and were used to perform GO annotations and KEGG pathway enrichment analysis with R software. The biological functions of KIF14 were verified with in vitro functional assay. 【Results】 KIF14 was highly expressed in ccRCC tissue and was positively correlated with clinical stage, pathological grade, and lymphatic metastasis, but negatively correlated with clinical prognosis. KIF14 expression was an independent risk factor for overall survival of ccRCC patients. GO annotations showed that KIF14 was involved in DNA replication, nuclear division, organelle fission, and cell adhesion. KEGG pathway enrichment analysis showed that KIF14 participated in cell cycle and p53 signaling pathway. Genemania analysis indicated KIF14 interacted with CENPE, CIT, KIF23, and other proteins. Timer showed that KIF14 was positively correlated with immune cell infiltration. Knockdown of KIF14 expression suppressed cell proliferation, migration, and invasion of ccRCC. 【Conclusions】 KIF14 may serve as a novel prognostic marker and a potential therapeutic target of clear cell renal cell carcinoma.

Research progress of ferroptosis in colorectal cancer / 国际生物医学工程杂志

Colorectal cancer is the third leading cause of cancer death worldwide and is characterized by frequent genetic mutations. Current chemotherapy, radiation, and surgical treatment options face challenges such as cancer recurrence and drug resistance. Treatment of colorectal cancer is often achieved by promoting various forms of programmed cell death. Iron death has been found to be an iron-dependent and lipid peroxide-driven form of programmed cell death. Studies suggest that iron death is an effective therapeutic strategy for colorectal cancer. However, a deeper understanding of the mechanisms of iron death onset, propagation, and drug resistance in colorectal cancer is needed. In this review paper, the mechanisms of iron death and its drug resistance pathways in colorectal cancer formation, metabolism, and treatment were reviewed, and future research directions were prospected to improve the treatment options for colorectal cancer.

The role of status-related neuronal ensembles in tem-poral lobe epilepsy / 中国药理学与毒理学杂志

OBJECTIVE Epileptic networks are char-acterized as two states,seizures or more prolonged inter-ictal periods.However,cellular mechanisms underlying the contribution of interictal periods to ictal events remain unclear.METHODS Here,we present the procedure for labeling seizure-activated and interictal-activated neuro-nal ensembles in mouse hippocampal kindling model using an enhanced-synaptic-activity-responsive element.This technique is combined with genetically encoded effectors to characterize and manipulate neuronal ensembles recruited by focal seizures(FS-Ens)and interictal periods(IP-Ens)in piriform cortex,a region that plays a key role in seizure generation.RESULTS Ca2+ activities and histo-logical evidence reveal a disjointed correlation between the two ensembles during FS dynamics.Optogenetic acti-vation of FS-Ens promotes further seizure development,while IP-Ens protects against it.Interestingly,both ensem-bles are functionally involved in generalized seizures(GS)due to circuit rearrangement.IP-Ens bidirectionally modulates FS but not GS by controlling coherence with hippocampus.CONCLUSION This study indicates that the interictal state may represent a seizure-preventing environment,and the interictal-activated ensemble may serve as a potential therapeutic target for epilepsy.

A1 astrocytes:A new target for the treatment of neurodegenerative and neuroinflammatory diseases / 实用医学杂志

Astrocytes constitute the most abundant cell type in the central nervous system.Under physi-ological conditions,astrocytes have a variety of functions,and play an important role in maintaining the homeostasis of the central nervous system.However,in response to insults such as injury,inflammation and hypoxia,astro-cytes undergo rapid changes in gene expression,morphology and function,and these responses collectively called as astrocyte reactivity.Activated astrocytes have been divided into neurotoxic phenotype(type A1)and neuropro-tective phenotype(type A2).Recent studies have shown that A1 astrocytes are widely involved in the occurrence and development of various central nervous system diseases.Therefore,targeted regulation of activated astrocytes by combining multiple techniques is expected to be a potential treatment for central nervous system diseases.Here,we review recent advances of A1 astrocytes,including the molecular mechanism of phenotypic transformation and its role in neurodegenerative and neuroinflammatory diseases.

Research progress of PROTACs in the treatment of prostate cancer / 中华泌尿外科杂志

The major challenges in drug therapy for prostate cancer are the ineffectiveness and resistance to androgen deprivation therapy, the low response to immunotherapy and the poor efficacy of small molecule targeted drugs. As a brand-new drug design concept, proteolysis targeting chimera (PROTAC) reveals its strength in the field of cancer treatment by connecting the target protein to the ubiquitin-proteasome system and triggering the degradation of the target protein. In recent years, basic medical research on targeting androgen receptors, cell proliferation, and transcriptional regulation proteins for the treatment of prostate cancer has achieved significant progress. Meanwhile, clinical trials related to PROTAC for the treatment of prostate cancer are gradually being carried out. In an era of big data and precision medicine, PROTAC is a breakthrough in the field of prostate cancer drug therapy. This article summarizes the fundamental principles of PROTACs and the basic and clinical research advances in the field of prostate cancer treatment.

Research progress on mechanisms and therapeutic drugs of peroxisome proliferator-activated receptor in treatment of cholestatic liver disease / 中国临床药理学与治疗学

Cholestatic liver disease is a common disease that causes bile flow dysfunction due to various reasons. The etiology of cholestatic liver disease is complexed, and therapeutic drugs are extremely limited. To date, ursodeoxycholic acid is the only FDA-approved drug for treating primary biliary cirrhosis, whereas its efficacy is limited to early stage of the disease, therefore novel drugs are urgently needed. Nuclear receptors become therapeutic hotspot target in cholestasis since these receptors play a key role in regulating bile acid homeostasis. Peroxisome proliferator-activated receptor (PPAR) is an important nuclear receptor involved in regulating multiple mechanisms of cholestasis in vivo. It can improve intrahepatic cholestasis by inhibiting bile acid synthesis, reducing bile acid toxicity, affecting the expression of bile acid metabolic enzymes and transporters, and can play an anti-inflammatory, anti-oxidation and anti-fibrosis role. A number of studies have shown that PPAR agonists represented by fibrates alone or in combination can improve liver function indexes, inflammatory factors and fibrosis markers in patients with cholestasis. This review analyzes and summarizes the lastest advances in the molecular mechanism of PPAR as a therapeutic target for cholestasis and drug treatment in development or have been used in clinical.

Expression and clinical significance of GBP1 in pulmonary tuberculosis / 安徽医科大学学报

Objective@#To investigate the expression pattern，underlying function and clinical significance of Guanylate-binding protein 1 ( GBP1) in pulmonary tuberculosis ( pTB) ．@*Methods@#Immunohistochemical staining was applied to detect the expression of GBP1 in pTB specimensand control samples． Combined with Gene Expression Omnibus ( GEO) datasets ，including GSE83456 and GSE34608，receiver operating characteristic ( ROC) curve was depicted to assess the diagnostic value of GBP1 in pTB．Then，the correlation between GBP1 and related regulatory factors was analyzed by protein-protein interaction network ( PPI) ; Finally，the potential molecular mechanism of GBP1 in pTB was probed by Gene Set Enrichment Analysis( GSEA) . @*Results@# Compared with the control group，GBP1 was significantly overexpressed in human pTB samples，including lung tissue and blood．The positive rate of GBP1 protein in pTB was 73. 9% . ROC curve analysis revealed that GBP1 might have important value in early diagnosis of pTB．GSEA analysis suggested that the hyper-expression of GBP1 was closely related to the host inflammatory response，IFN-γ/ α signaling pathway and TNF-α/ IL-6 signal transduction．@*Conclusion@# GBP1 is highly expressed in pTB tissues and is involved in the process of inflammatory response and host anti-tuberculosis infection ; GBP1 may be used as an early diagnostic marker or therapeutic target for pTB.

Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure. Recently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3K/AKT in fibrotic processes is increasingly prominent, with PI3K/AKT inhibitors currently under clinical evaluation in IPF. Therefore, PI3K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.

The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.

Human islet amyloid polypeptide:A therapeutic target for the management of type 2 diabetes mellitus / 药物分析学报

Type 2 diabetes mellitus(T2DM)and other metabolic disorders are often silent and go unnoticed in patients because of the lack of suitable prognostic and diagnostic markers.The current therapeutic regimens available for managing T2DM do not reverse diabetes;instead,they delay the progression of diabetes.Their efficacy(in principle)may be significantly improved if implemented at earlier stages.The misfolding and aggregation of human islet amyloid polypeptide(hIAPP)or amylin has been associated with a gradual decrease in pancreatic β-cell function and mass in patients with T2DM.Hence,hIAPP has been recognized as a therapeutic target for managing T2DM.This review summarizes hIAPP's role in mediating dysfunction and apoptosis in pancreatic β-cells via induction of endoplasmic reticulum stress,oxidative stress,mitochondrial dysfunction,inflammatory cytokine secretion,autophagy blockade,etc.Furthermore,it explores the possibility of using intermediates of the hIAPP aggregation pathway as potential drug targets for T2DM management.Finally,the effects of common antidiabetic molecules and repurposed drugs;other hIAPP mimetics and peptides;small organic molecules and natural compounds;nanoparticles,nanobodies,and quantum dots;metals and metal complexes;and chaperones that have demonstrated potential to inhibit and/or reverse hIAPP aggregation and can,therefore,be further developed for managing T2DM have been discussed.

Lipid markers and targets of coronary artery disease based on lipidomics / 药学学报

Coronary artery disease is the leading cause of death worldwide, the coronary artery stenosis or occlusion caused by atherosclerosis leads to myocardial ischemia, hypoxia, or necrosis, that is main histopathological features of coronary artery disease. Atherosclerosis relates closely to abnormal lipid regulation, chronic inflammation, and endothelial dysfunction. Cardiac enzymes and high, low-density lipoprotein are currently used to diagnose a variety of coronary artery diseases, but the evidence is inadequate. Thus, new cardioprotective therapies are required to explore sensitive molecular markers for the prediction of cardiovascular events. Lipids have an important role in maintaining the myocardial cell structure as well as cardiac function. Lipidomics is a newly emerged discipline that studies lipids on a large scale. Recent advancements in lipidomics on coronary artery disease have shown that certain lipids, such as ceramide, sphingosine, lysophosphatidic acid, oxidized lipids, and so on, are associated with the clinical classification and characteristics of coronary artery disease. In addition, recent studies of lipid profiles of the cardiac, fat, liver, and other tissue samples in animal models also have provided a novel viewpoint. Given the increasing application of lipidomics techniques for coronary artery disease, we provide a review of lipidomics technology, sensitive lipid markers, recent studies of therapeutic targets, and drug discovery for coronary artery disease.

Mechanisms of Dangua Recipe in Improving Glycolipid Metabolic Disorders Based on Transcriptomics / 中国结合医学杂志

OBJECTIVE@#To explore the mechanisms of Dangua Recipe (DGR) in improving glycolipid metabolism based on transcriptomics.@*METHODS@#Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table, including a conventional diet group (Group A), a DGR group (Group B, high-calorie diet + 20.5 g DGR), and a high-calorie fodder model group (Group C). After 12 weeks of intervention, the liver tissue of rats was taken. Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy, and then gene or protein validation of liver tissue were performed. Nicotinamide phosphoribosyl transferase (Nampt) and phosphoenolpyruvate carboxykinase (PEPCK) proteins in liver tissues were detected by enzyme linked immunosorbent assay, fatty acid synthase (FASN) protein was detected by Western blot, and fatty acid binding protein 5 (FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction. Furthermore, the functional verification was performed on the diabetic model rats by Nampt blocker (GEN-617) injected in vivo. Hemoglobin A@*RESULTS@#Totally, 257 differential-dominant genes of Group A vs. Group C and 392 differential-dominant genes of Group B vs. Group C were found. Moreover, 11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs. Group C and Group C vs. Group B were confirmed. The liver tissue target validation showed that Nampt, FASN, PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome. The in vivo functional tests showed that GEN-617 increased body weight, HbA@*CONCLUSION@#Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.

Mechanism of Triclosan in the Treatment of Nonalcoholic Fatty Liver Disease Based on Network Pharmacology / 中国医学科学院学报

Objective To explore the potential targets of triclosan in the treatment of nonalcoholic fatty liver disease(NAFLD) and to provide new clues for the future research on the application of triclosan. Methods The targets of triclosan and NAFLD were obtained via network pharmacology.The protein-protein interaction network was constructed with the common targets shared by triclosan and NAFLD.The affinity of triclosan to targets was verified through molecular docking.Gene ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out to analyze the key targets and the potential mechanism of action.NAFLD model was established by feeding male C57BL/6J mice with high-fat diet for 12 weeks.The mice were randomly assigned into a model group and a triclosan group [400 mg/(kg·d),gavage once a day for 8 weeks].The hematoxylin-eosin(HE) staining was used for observation of the pathological changes and oil red O staining for observation of fat deposition in mouse liver.Western blotting was employed to detect the protein level of peroxisome proliferator-activated receptor alpha(PPARα) in the liver tissue. Results Triclosan and NAFLD had 34 common targets,19 of which may be the potential targets for the treatment,including albumin(ALB),PPARα,mitogen-activated protein kinase 8(MAPK8),and fatty acid synthase.Molecular docking predicted that ALB,PPARα,and MAPK8 had good binding ability to triclosan.KEGG pathway enrichment showcased that the targets were mainly enriched in peroxisome proliferator-activated receptor signaling pathway,in which ALB and MAPK8 were not involved.Triclosan alleviated the balloon-like change and lipid droplet vacuole,decreased the lipid droplet area,and up-regulated the expression level of PPARα in mouse liver tissue. Conclusion PPARα is a key target of triclosan in the treatment of NAFLD,which may be involved in fatty acid oxidation through the peroxisome proliferator activated receptor signaling pathway.

Expression and clinical significance of silencing kinesin KIF4A in thyroid cancer / 国际生物医学工程杂志

Objective:To investigate the expression of silencing kinesin KIF4A in thyroid cancer tissues and its relationship with clinicopathological characteristics of thyroid cancer patients, and to assess the role of KIF4A in the progression of thyroid cancer.Methods:The expression of KIF4A in normal thyroid tissues and the thyroid cancer population and its relationship with disease-free survival of patients were analyzed online by gene expression interaction analysis (GEPIA) database, and the expression of KIF4A in tumor tissues and paraneoplastic tissues of thyroid cancer patients was assessed by immunohistochemical assays. The patients were divided into high- and low-expression groups according to the staining intensity, and the correlation between the expression of KIF4A and clinicopathological features was analyzed. The effect of KIF4A on the proliferation of thyroid cancer cells was explored by a clone formation assay and an MTT assay.Results:According to the analysis of the web-based database, KIF4A showed significantly high expression in human thyroid cancer tissues, and disease-free survival was significantly lower in highly expressed patients. The results of the case analysis showed that the correlation between KIF4A expression intensity and gender, age, and lymph node metastasis in thyroid cancer patients was not statistically significant (all P>0.05), and the correlation with TNM stage and intraglandular dissemination was statistically significant (all P<0.05). The results of the colony formation assay and the MTT assay showed that the expression of KIF4A promoted the proliferation of thyroid cancer cells ( P<0.05). Conclusions:KIF4A can promote the progression of thyroid cancer and has the potential to become a new therapeutic target for thyroid cancer.