The receptor for β2GPⅠon membrane of hepatocellular carcinoma cell line SMMC-7721 is annexin Ⅱ

AIM: To evaluate the receptor protein which can specifically bind to β2GPⅠon the membrane of hepatocellular carcinoma (HCC) cell line SMMC-7721, and to study the biological function of the receptor.METHODS: Through β2GPⅠ-affinity chromatography column, the peptid-polysome-mRNA complex, which can specially bind to β2GPⅠ, stayed with the column and was separated from the whole polysome of liver cells, and then eluted and collected. Using cDNA synthesis kit and cDNA PCR kit, the corresponding cDNA was obtained and sequenced. RT-PCR was used to amplify annexinⅡ, and flow cytometry was used to study the competitive binding of annexinⅡ with β2GPⅠto SMMC-7721.RESULTS: A total of 1.1 kb of the cDNA fragment of the specific binding protein of β2GPⅠon liver cell membrane was obtained. The sequence of cDNA shared high homology with human annexinⅡ (98%). AnnexinⅡ was expressed on the membrane of SMMC-7721, and could compete with β2GPⅠfor combining with SMMC-7721.CONCLUSION: The receptor for β2GPⅠon membrane of SMMC-7721 cells is annexinⅡ, which might bridge HBV to infect hepatocytes.

Small RNA sequencing revealed aberrant piRNA expression profiles in deciduas of recurrent spontaneous abortion patients

Piwi-interacting RNAs(piRNAs)is a novel class of non-coding RNAs.However,changes in piRNA expression profiles in recurrent spontaneous abortion(RSA)have not yet been investigated.The aim of this study was to identify differentially expressed piRNAs in deciduas of RSA patients.Decidua tissues were collected by curettage from recruited RSA patients and normal early pregnant(NEP)women with their informed consent.Small RNA sequencing was used to evaluate the differences in piRNA expression profiles between RSA and NEP.The present results demonstrated that the counts of total piRNA reads in RSA samples were increased compared with those in NEP samples(0.21%vs.0.11%).Differential expression analysis identified 29 upregulated piRNAs and 18 downregulated piRNAs in RSA samples.RT-qPCR further confirmed that the expression levels of uniq-109625,uniq-89328,uniq-50651 and uniq-4569 were decreased in 8 RSA tissues,compared with 13 NEP tissues.Otherwise,pi-22628 and uniq-173406 were increased in 8 RSA tissues.Based on GO term and KEGG pathway analysis,we speculate that these piRNAs regulate RSA by targeting extracellular matrix component pathway,cell adhesion pathway and focal adhesion pathway.PiRNAs may be involved in RSA pathogenesis by target genes function on adhesion and extracellular matrix component.

Association of KIR Genotypes and Haplotypes with Susceptibility to Chronic Hepatitis B Virus Infection in Chinese Han Population

Killer immunoglobulin-like receptor (KIR) genes can regulate the activation of NK and T cells upon interaction with HLA class I molecules. Hepatitis B virus (HBV) infection has been regarded as a multi-factorial disorder disease. Previous studies revealed that KIRs were involved in HCV and HIV infection or clearance. The aim of this study was to explore the possibility of the inheritance of KIR genotypes and haplotypes as a candidate for susceptibility to persistent HBV infection or HBV clearance. The sequence specific primer polymerase chain reaction (SSP-PCR) was employed to identify the KIR genes and pseudogenes in 150 chronic hepatitis B (CHB) patients, 251 spontaneously recovered (SR) controls, and 412 healthy controls. The frequencies of genotype G, M, FZ1 increased in CHB patients compared with healthy control subjects. The frequency of genotype AH was higher in SR controls than that in both CHB patients and healthy controls. The carriage frequencies of genotype G and AH were higher; while, the frequencies of AF and AJ were lower in SR controls than those in healthy control subjects. The frequency of A haplotype was lower, whereas, the frequency of B haplotype was higher in CHB patients and SR controls than those in healthy controls. In healthy controls, haplotype 4 was found lower compared with that in CHB patients and SR controls and the frequency of haplotype 5 was higher in SR controls than that in other two groups. Based on these findings, it seems that the genotypes M and FZ1 are HBV susceptive genotypes; AH, on the other hand, may be protective genotypes that facilitate the clearance of HBV. It appears that the haplotype 4 is HBV susceptive haplotype, whereas, haplotype 5 may be the protective haplotype that facilitates the clearance of HBV.

Snail promotes metastasis of nasopharyngeal carcinoma partly by down-regulating TEL2

Background:Metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma(NPC).We previously reported that TEL2,a negative regulator of SERPINE1,could inhibit NPC metastasis to lymph nodes.Method:A series of in vivo and in vitro assays were performed to elucidate the regulation between Snail and TEL2.TEL2 expression was analyzed in three representative NPC cell lines expressing low levels of Snail(S26,6-10B,HK1)and two cell lines expressing high levels of Snail(S18,5-8F).Luciferase and chromatin immunoprecipitation assays were used to analyze the interaction between Snail and TEL2.The roles of the Snail/TEL2 pathway in cell migration and invasion of NPC cells were examined using transwell assays.Metastasis to the lungs was examined using nude mouse receiving NPC cells injection through the tail vein.Results:Ectopic Snail expression down-regulated TEL2 at the mRNA and protein levels,whereas knockdown of Snail using short hairpin RNA up-regulated TEL2.Luciferase and chromatin immunoprecipitation assays indicated that Snail binds directly to the TEL2 promoter.Ectopic Snail expression enhanced migration and invasion of NPC cells,and such effects were mitigated by TEL2 overexpression.TEL2 overexpression also attenuated hypoxia-induced cell migration and invasion,and increased the number of metastatic pulmonary nodules.Snail overexpression reduced the number of metastatic pulmonary nodules.Conclusions:TEL2 is a novel target of Snail and suppresses Snail-induced migration,invasion and metastasis in NPC.

Rational design of hydrogels for immunomodulation

The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development,repair and regeneration.Traditional immunomodulatory biologics exhibit limitations including degradation by enzymes,short half-life and lack of targeting ability.Encapsulating or binding these biologics within biomaterials is an effective way to address these problems.Hydrogels are promising immunomodulatory materials because of their prominent biocompatibility,tuneability and versatility.However,to take advantage of these opportunities and optimize material performance,it is important to more specifically elucidate,and leverage on,how hydrogels affect and control the immune response.Here,we summarize how key physical and chemical properties of hydrogels affect the immune response.We first provide an overview of underlying steps of the host immune response upon exposure to biomaterials.Then,we discuss recent advances in immunomodulatory strategies where hydrogels play a key role through(i)physical properties including dimensionality,stiffness,porosity and topography;(ii)chemical properties including wettability,electric property and molecular presentation;and(iii)the delivery of bioactive molecules via chemical or physical cues.Thus,this review aims to build a conceptual and practical toolkit for the design of immune-instructive hydrogels capable of modulating the host immune response.

Protective effects and mechanisms of Lizhong decoction(理中汤) against non-alcoholic fatty liver disease in a rat model

OBJECTIVE: To investigate the protective effects and molecular mechanisms of Lizhong decoction( 理中汤, LZD) against non-alcoholic fatty liver disease(NAFLD). METHODS: Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD, and were administered LZD by gavage for four weeks. Potential therapeutic targets for NAFLD were analyzed using network pharmacology. Liver pathology was evaluated using Oil Red O and hematoxylin-eosin staining. Furthermore, mitochondrial function, lipid metabolism, oxidative stress, and inflammatory response were examined. RESULTS: Rats with NAFLD exhibited high levels of hepatic damage and cholesterol deposition. Moreover, apoptosis was increased, superoxide dismutase and glutathione content were reduced, malondialdehyde content was increased, and the protein expression of inflammatory cytokines and p-c-Jun N-terminal kinase was increased. The LZD treatment ameliorated mitochondrial dysfunction, reduced liver damage,inhibited oxidative stress and inflammatory response, upregulated peroxisome proliferator-activated receptor(PPAR)-γ expression, and suppressed dipeptidyl peptidase 4(DPP4) expression in the liver. CONCLUSION: It was found that LZD alleviates NAFLD by activating PPAR-γ and inhibiting DPP4.