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Golgi protein 73 (also known as GP73 or GOLPH2) is a transmembrane glycoprotein present in the Golgi apparatus. In diseased states, GP73 is expressed by hepatocytes rather than by bile duct epithelial cells. Many studies have reported that serum GP73 (sGP73) is a marker for hepatocellular carcinoma (HCC). For HCC diagnosis, the sensitivities of sGP73 were higher than that of other markers but the specificities were lower. Considering that the concentration of GP73 is consistent with the stage of liver fibrosis and cirrhosis, some studies have implied that GP73 may be a marker for liver fibrosis and cirrhosis. Increased sGP73 levels may result from hepatic inflammatory activity. During liver inflammation, GP73 facilitates liver tissue regeneration. By summarizing the studies on GP73 in liver diseases, we wish to focus on the mechanism of GP73 in diseases., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2022 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background & Aims: Hepatic fibrosis is characterized by hepatic stellate cell (HSC) activation and transdifferentiation-mediated extracellular matrix (ECM) deposition, which both contribute to cirrhosis. However, no antifibrotic regimen is available in the clinic. microRNA-23b/27b/24-1 cluster inhibition of transforming growth factor-β (TGF-β) signaling during hepatic development prompted us to explore whether this cluster inhibits HSC activation and hepatic fibrosis., Methods: Experimental fibrosis was studied in carbon tetrachloride (CCl 4 )-treated C57BL/6 mice. After administration of miR-23b/27b/24-1 lentivirus or vehicle, animals were euthanized for liver histology. In primary rat HSC and HSC-T6, the anti-fibrotic effect of miR-23b/27b/24-1 cluster was furtherly investigated by RNA-sequencing, luciferase reporter assay, western blotting and bioinformatic means., Results: In this study, we showed that increasing the miR-23b/27b/24-1 level through intravenous delivery of miR-23b/27b/24-1 lentivirus ameliorated mouse hepatic fibrosis. Mechanistically, the miR-23b/27b/24-1 cluster directly targeted messenger RNAs, which reduced the protein expression of 5 secretory profibrotic genes (TGF-β2, Gremlin1, LOX, Itgα2, and Itgα5) in HSCs. Suppression of the TGF-β signaling pathway by down-regulation of TGF-β2, Itgα2, and Itgα5, and activation of the bone morphogenetic protein signaling pathway by inhibition of Gremlin1, decreased extracellular matrix secretion of HSCs. Furthermore, down-regulation of LOX expression softened the ECM. Moreover, a reduction in tissue inhibitors of metalloproteinase 1 expression owing to weakened TGF-β signaling increased ECM degradation., Conclusions: Hepatic overexpression of the miR-23b/27b/24-1 cluster blocked hepatic fibrosis and may be a novel therapeutic regimen for patients with hepatic fibrosis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

E proteins are transcriptional regulators that regulate many developmental processes in animals and lymphocytosis and leukemia in Homo sapiens. In particular, E2A, a member of the E protein family, plays a major role in the transcriptional regulatory network that promotes the differentiation and development of B and T lymphocytes. E2A-mediated transcriptional regulation usually requires the formation of E2A dimers, which then bind to coregulators. In this review, we summarize the mechanisms by which E2A participates in transcriptional regulation from a structural perspective. More specifically, the C-terminal helix-loop-helix (HLH) region of the basic HLH (bHLH) domain first dimerizes, and then the activation domains of E2A bind to different coactivators or corepressors in different cell contexts, resulting in histone acetylation or deacetylation, respectively. Then, the N-terminal basic region (b) of the bHLH domain binds to or dissociates from a specific DNA motif (E-box sequence). Last, trans-activation or trans-repression occurs. We also summarize the properties of these E2A domains and their interactions with the domains of other proteins. The feasibility of developing drugs based on these domains is discussed., (© 2021. The Author(s).)

Hepatic fibrosis (HF) is the process of fibrous scar formation caused by chronic liver injury of different etiologies. Previous studies have hypothesized that the activation of hepatic stellate cells (HSCs) is the central process in HF. The interaction between HSCs and surrounding cells is also crucial. Additionally, hepatic sinusoids capillarization, inflammation, angiogenesis and fibrosis develop during HF. The process involves multiple cell types that are highly connected and work in unison to maintain the homeostasis of the hepatic microenvironment, which serves a key role in the initiation and progression of HF. The current review provides novel insight into the intercellular interaction among liver sinusoidal endothelial cells, HSCs and Kupffer cells, as well as the hepatic microenvironment in the development of HF.

Objective: To analyze differentially expressed genes (DEGs) related to liver fibrosis, and clarify the key genes and the possible targets in the progression of liver fibrosis., Methods: Using microarray datasets, GSE38199 was extracted from Gene Expression Omnibus (GEO), and a bioinformatics method was performed to find DEGs and transcription factors related to liver fibrosis., Results: A total of 58 DEGs were screened out according to GEO2R online analysis tool, which included 49 up-regulated and 9 down-regulated genes. These DEGs were mainly involved in formation with the extracellular region and extracellular exosome through gene ontology (GO) enrichment analysis. Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis showed that DEGs mainly participated in the PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, and metabolic pathways. Based on the results of the Protein-Protein Interaction (PPI) network and Molecular Complex Detection (MCODE) analysis, 9 key genes ( COL1A1, FBN1, BGN, COL6A3, MMP2, FBLN5, LUM, PDGFRB, LOXL1 ) were screened out. A total of 30 transcription factors were found according to these 9 key genes, of which 4 transcription factors (Stat3, Trp53, NF-κB1, Sp1) were enriched., Conclusion: Stat3, Trp53, NF-κB1, and Sp1 were all related to the development of liver fibrosis, and FBLN5 might be a target for liver fibrosis., Competing Interests: None., (IJCEP Copyright © 2021.)

G-quadruplexes form folded structures because of tandem repeats of guanine sequences in DNA or RNA. They adopt a variety of conformations, depending on many factors, including the type of loops and cations, the nucleotide strand number, and the main strand polarity of the G-quadruplex. Meanwhile, the different conformations of G-quadruplexes have certain influences on their biological functions, such as the inhibition of transcription, translation, and DNA replication. In addition, G-quadruplex binding proteins also affect the structure and function of G-quadruplexes. Some chemically synthesized G-quadruplex sequences have been shown to have biological activities. For example, bimolecular G-quadruplexes of AS1411 act as targets of exogenous drugs that inhibit the proliferation of malignant tumours. G-quadruplexes are also used as vehicles to deliver nanoparticles. Thus, it is important to identify the factors that influence G-quadruplex structures and maintain the stability of G-quadruplexes. Herein, we mainly discuss the factors influencing G-quadruplexes and the synthetic G-quadruplex, AS1411. SIGNIFICANCE OF THE STUDY: This review summarizes the factors that influence G-quadruplexes and the functions of the synthetic G-quadruplex, AS1411. It also discusses the use of G-quadruplexes for drug delivery in tumour therapy., (© 2020 The Authors. Cell Biochemistry and Function published by John Wiley & Sons Ltd.)

Objective: To investigate the efficacy and safety of LOP（asparaginase + vincristine + dexamethasone） chemotherapy combined with radiotherapy in patients with nasal NK/T cell lymphoma. Method: Sixty patients with nasal NK/T cell lymphoma admitted to our hospital from February 2012 to February 2016 were selected as the study subject. They were randomly divided into group A and group B, 30 cases in each group. All patients were treated with combined chemotherapy and IMRT（intensity modulated conformal radiotherapy）. The LOP regimen was used in group A and the CHOP（cyclophosphamide + pirarubicin + vincristine + dexamethasone） regimen was used in group B. The short-term efficacy, long-term efficacy and adverse reactions of the two groups were compared. Result: The clinical manifestations of 60 patients mainly included nasal obstruction（81.67%）, accompanied by fever, headache, nosebleed and runny nose. Forty-one patients（68.33%） had only one site of lesion, and 21 patients（35.00%） had multiple sites of lesions. In terms of total remission rate, it was significantly higher in group A than that in group B（93.33% vs. 66.67%, P <0.05）. In terms of adverse reactions, the incidence of bone marrow suppression, gastrointestinal reaction and low-protein reaction was significantly lower in group A than that in group B（ P <0.05）. Three patients died in group A and 11 patients died in group B during the 3-year follow-up. The 3-year survival rate of group A was higher than that of group B（ P <0.05）. Conclusion: Compared with CHOP+IMRT regimen, the LOP+IMRT regimen for nasal NK/T-cell lymphoma patients resulted in higher overall remission rate, survival rate and lower adverse reactions, so it is worth in clinical promotion., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Introduction: As 'chemical antibodies', aptamers have some advantages, such as lack of immunogenicity, rapid tissue penetration, cell internalization and so on. Consequently, more and more aptamers have been screened out by the systematic evolution of ligands through exponential enrichment for the desired cells or membrane receptors. On the basis of the result, researchers use aptamers to guide drug targeting to the desired cells and internalization in vivo., Areas Covered: In this review, we explore the mechanisms of cargo- or aptamer-mediated internalization, and then briefly summarize five strategies for exploring the mechanism of aptamer internalization. Finally, we focus on four types of applications involving aptamer internalization: aptamers as drugs, aptamers as chemical drug-delivery systems, aptamer-based chimeras and aptamer-conjugated nanoparticles or block copolymer micelles., Expert Opinion: Two aptamer-internalization mechanisms are known, namely receptor-mediated endocytosis and macropinocytosis. The latter mechanism, which is has only been verified in the internalization of nucleolin aptamer shuttles between the nucleus and cytoplasm, may be important for nuclear internalization and cargo molecule escape from the endosomal compartment. Thus, it is feasible to use some strategies to further explore the macropinocytosis internalization mechanism and then to screen for aptamers similar to the nucleolin aptamer for use with the desired cell types as a targeted delivery tool.

Objective: To analyze the clinical characteristics and prognosis of sudden sensorineural hearing loss (SSNHL) with metabolic syndrome (MetS). Method: Records of 212 patients with SSNHL treated in our department were retrospectively reviewed, including gender, age,course of the disease, concomitant time of tinnitus and vertigo, concomitant rate of hypertension and diabetes mellitus, BMI, systolic pressure, diastolic pressure, HDL-C, TG, fasting plasma glucose level, severity of hearing loss and audiograms. All patients were divided into two groups, the MetS group and the Non-MetS group, and the clinical characteristics and prognosis between two groups were compared. Result: In the MetS group, the BMI, systolic pressure, TG, fasting plasma glucose level were higher than that in the Non-MetS group, while the HDL-C level was lower than that in Non-MetS group ( P <0.01), and the rates of profound hearing loss, flat audiogram and total deafness audiogram were higher than that in the Non-MetS group ( P <0.05). In the MetS group, the overall recovery rate, complete recovery rate and marked recovery rate were 57.8%,6.0% and 14.5%, respectively, which was lower than that in the Non-MetS group (79.8%,19.4% and 27.9%, P <0.05 ). Conclusion: SSNHL patients with MetS suffered a severer hearing loss, the most audiograms were flat and total deafness, and the prognosis of SSNHL patients with MetS was poorer., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate gene or protein expression; however, their function in the progression of hepatic fibrosis remains unclear. Hepatic fibrosis is a continuous wound-healing process caused by numerous chronic hepatic diseases, and the activation of hepatic stellate cells (HSCs) is generally considered to be a pivotal step in hepatic fibrosis. In the process of hepatic fibrosis, some lncRNAs regulates diverse cellular processes. Here are several examples: the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and liver fibrosis-associated lncRNA1 (lnc-LFAR1) promote HSC activation in the progression of hepatic fibrosis via the transforming growth factor-β signaling pathway; the lncRNA HIF 1 alpha-antisense RNA 1 (HIF1A-AS1) and Maternally expressed gene 3 reduce HSC activation which are associated with DNA methylation; the lncRNA plasmacytoma variant translocation 1, Homeobox (HOX) transcript antisense RNA and MALAT1 promote HSC activation as competing endogenous RNAs (ceRNAs); the long intergenic non-coding RNA-p21 (lncRNA-p21) and Growth arrest-specific transcript 5 reduce HSC activation as ceRNAs. As we get to know more about the function of lncRNAs in hepatic fibrosis, more and more ideas for the molecular targeted therapy in hepatic fibrosis will be put forward.

Increasing evidence indicates that embryonic stem cell specific microRNAs (miRNAs) play an essential role in the early development of embryo. Among them, the miR-290-295 cluster is the most highly expressed in the mouse embryonic stem cells and involved in various biological processes. In this paper, we reviewed the research progress of the function of the miR-290-295 cluster in embryonic stem cells. The miR-290-295 cluster is involved in regulating embryonic stem cell pluripotency maintenance, self-renewal, and reprogramming somatic cells to an embryonic stem cell-like state. Moreover, the miR-290-295 cluster has a latent pro-survival function in embryonic stem cells and involved in tumourigenesis and senescence with a great significance. Elucidating the interaction between the miR-290-295 cluster and other modes of gene regulation will provide us new ideas on the biology of pluripotent stem cells. In the near future, the broad prospects of the miRNA cluster will be shown in the stem cell field, such as altering cell identities with high efficiency through the transient introduction of tissue-specific miRNA cluster.

When hepatocytes are damaged severely, a variety of signaling pathways will be triggered by inflammatory factors and cytokines involving in the process of hepatic fibrosis. The microRNA (miRNA) family consists of several miRNAs which have the potential for synergistic regulation of these signaling pathways. However, it is poor to understand the roles of miRNA family as a whole in hepatic fibrosis. Increasing studies have suggested several miRNA families are related with activation of hepatic stellate cells and hepatic fibrosis through cooperatively regulating certain signaling pathways. During the process of hepatic fibrosis, miR-29 family primarily induces cell apoptosis by modulating phosphatidylinositol 3-kinase/AKT signaling pathway and regulates extracellular matrix accumulation. miR-34 family promotes the progression of hepatic fibrosis by inducing activation of hepatic stellate cells, while miR-378 family suppresses the process in Glis dependent manner. miR-15 family mainly promotes cell proliferation and induces apoptosis. The miR-199 family and miR-200 family are responsible for extracellular matrix deposition and the release of pro-fibrotic cytokines. These miRNA family members play pro-fibrotic or anti-fibrotic roles by targeting genes collectively or respectively which involve in hepatic fibrosis related signaling pathways and hepatic stellate cell activation. Thus, good understandings of molecular mechanisms which are based on miRNA families may provide new ideas for the molecular targeted therapy of hepatic fibrosis in the future.

Aim: To determine the role of Notch1 and Hes1 in regulating the activation of hepatic stellate cells (HSCs) and whether Hes1 is regulated by transforming growth factor (TGF)/bone morphogenetic protein (BMP) signaling., Methods: Immunofluorescence staining was used to detect the expression of desmin, glial fibrillary acidic protein and the myofibroblastic marker α-smooth muscle actin (α-SMA) after freshly isolated, normal rat HSCs had been activated in culture for different numbers of days (0, 1, 3, 7 and 10 d). The expression of α-SMA, collagen1α2 (COL1α2), Notch receptors (Notch1-4), and the Notch target genes Hes1 and Hey1 were analyzed by reverse transcriptase-polymerase chain reaction. Luciferase reporter assays and Western blot were used to study the regulation of α-SMA, COL1α1, COL1α2 and Hes1 by NICD1, Hes1, CA-ALK3, and CA-ALK5 in HSC-T6 cells. Moreover, the effects of inhibiting Hes1 function in HSC-T6 cells using a Hes1 decoy were also investigated., Results: The expression of Notch1 and Hes1 mRNAs was significantly down-regulated during the culture of freshly isolated HSCs. In HSC-T6 cells, Notch1 inhibited the promoter activities of α-SMA, COL1α1 and COL1α2. On the other hand, Hes1 enhanced the promoter activities of α-SMA and COL1α2, and this effect could be blocked by inhibiting Hes1 function with a Hes1 decoy. Furthermore, co-transfection of pcDNA3-CA-ALK3 (BMP signaling activin receptor-like kinase 3) and pcDNA3.1-NICD1 further increased the expression of Hes1 compared with transfection of either vector alone in HSC-T6 cells, while pcDNA3-CA-ALK5 (TGF-β signaling activin receptor-like kinase 5) reduced the effect of NICD1 on Hes1 expression., Conclusion: Selective interruption of Hes1 or maintenance of Hes1 at a reasonable level decreases the promoter activities of α-SMA and COL1α2, and these conditions may provide an anti-fibrotic strategy against hepatic fibrosis.

Previous studies have shown that regulation of the epidermal growth factor gene (EGFR) pathway plays a role in glioma progression. Certain genotypes of the EGFR gene may be related to increased glioblastoma risk, indicating that germ line EGFR polymorphisms may have implications in carcinogenesis. To examine whether and how variants in the EGFR gene contribute to glioma susceptibility, we evaluated nine tagging single-nucleotide polymorphisms (tSNPs) of the EGFR gene in a case-control study from Xi'an city of China (301 cases, 302 controls). EGFR SNP associations analyses were performed using SPSS 16.0 statistical packages, PLINK software, Haploview software package (version 4.2) and SHEsis software platform. We identified two susceptibility tSNPs in the EGFR gene that were potentially associated with an increased risk of glioma (rs730437, p = 0.016; OR: 1.32; 95%CI: 1.05-1.66 and rs1468727, p = 0.008; OR: 1.31; 95%CI: 1.04-1.65). However, after a strict Bonferroni correction analysis was applied, the significance level of the association between EGFR tSNPs and risk of glioma was attenuated. We observed a protective effect of haplotype "AATT" of the EGFR gene, which was associated with a 29% reduction in the risk of developing glioma, while haplotype "CGTC" increased the risk of developing glioma by 36%. Our results, combined with previous studies, suggested an association between the EGFR gene and glioma development.

Objective: To study the characteristics of head and neck lymphoma in order to improve its diagnose rate., Methods: Review and analysis 170 patients with head and neck lymphoma in department of otolaryngology of Xiangya hospital from 1997 to 2005., Results: Nasal cavity and nasal sinuses, neck, tonsil were the common place of the origin of head and neck lymphoma. There are 9 cases Hodgkin disease and 161 cases non-Hodgkin lymphoma (NHL). T cellularity, B cellularity lymphoma, the mixed pattern and nullityping accounted for 60.9%, 36.0% and 3.1% of these patients with NHL, respectively. CHOP and radiotherapy were the main treatment method., Conclusion: The clinical and imageology manifestation of head and neck lymphoma were of diversification and no specificity, whose final diagnosis depended on immunohistochemistry.

Objective: To investigate the feasibility of transplanted endothelial progenitor cells transfected with VEGF165 gene to ischemic flap with increased neovascularization and augmented the survival areas., Methods: EPCs were isolated from human cord blood and cultured in vitro. Plasmid PcDNA3.1(-)/VEGF165 containing VEGF gene was transfected into the EPCs. EPCs transfected with blank plasmid, and EPCs without transfection were used as controls. ELISA was used to detect the expression of VEGF protein in the culture fluids. The EPCs were dyed with CM-DiI 7 days later. Ischemic skin flaps were made on the backs of 27 nude mice. The mice were randomly divided into 3 equal groups with their skin flaps being transplanted with EPCs transfected with 3.1(-)/VEGF165 plasmid, EPCs not transfected with 3.1(-)/VEGF165 plasmid, and injected with M199 medium at the basal part. Four days after the peduncles of the skin flaps were cut. Seven days after the cutting-off of the peduncles the survival rate of skin flap was observed and the blood perfusion was observed with laser Doppler flowmetry, 10 days after the density of capillary arteries were observed with microcirculation microscope. Three specimens of skin flap were taken 7 and 11 days after the skin flaps were made to undergo histological examination to detect the density of capillary arteries by CD34 immunohistochemistry and to observe the proliferation of EPCs with fluorescence microscopy. Peripheral blood samples were collected 1, 4, 7, 14, and 28 days after the skin flaps were made to undergo ELISA to detect the levels of VEGF protein, Results: The VEGF levels in the culture supernatants of the groups A, B, and C were 352 ng/L +/- 35 ng/L, 45 ng/L +/- 5 ng/L, and 0 ng/L respectively with significant difference between any 2 groups (all P < 0.05). The skin flap survival rates of the three groups were 97.2%, 60.3%, and 34.2% respectively with significant difference between any 2 groups (all P < 0.05) and the survival quality of the group A was the best. The capillary density of the group A was greater than those of the groups B and C. The VEGF levels at any time point of the group A were all significantly higher than those of the group B and C (all P < 0.05) and there was not a significant difference between the groups B and C. The capillary density levels at different time points decreased progressively in the order of groups A, B, and C with significant difference between any 2 groups (all P < 0.05). No EPC was shown by fluorescence microscopy in the skin flaps of the group C. The EPC density in skin flap 7 and 11 days after the flaps were made were 136 +/- 10 and 75 +/- 6/mm(2) and 305 +/- 26 and 199 +/- 18/mm(2) respectively with significant differences between the groups A and B. (both P < 0.05)., Conclusion: The EPCs from human cord blood, especially those transfected with VEGF165 gene increases the neovascularization in ischemic skin flaps and augments their survival rate.

Objective: To evaluate the effect of Xuesaitong injection (XSTI, a preparation of Panax Notoginseng) as auxilliary treatment of severe craniocerebral injury., Methods: Eighty-seven patients with severe craniocerebral injury were selected and randomly divided into the treated group (n = 44) and the control group (n = 43), they were treated with conventional treatment, and XSTI was given additionally to the treated group. Intracranial pressure (ICP) and Glasgow coma score (GCS) of all patients were measured after 1 or 2-week treatment, and Glasgow outcome scale (GOS) of them was determined 3 months later. Then the therapeutic effect in the two groups were compared., Results: After treatment, the ICP was lower, GCS higher and GOS better in the treated group than those in the control group significantly, all showing statistical significance (P < 0.05)., Conclusion: XSTI has marked clinical therapeutic effect in treating patients with severe craniocerebral injury.