Comparison of Different Intraocular Lens Power Calculation Formulas in Eyes with Primary Angle Closure.

PURPOSE: To compare the accuracy of six intraocular lens power calculation formulas, Barrett Universal Ⅱ (BU Ⅱ), Haigis, Hoffer QST, HolladayⅠ, Kane and SRK/T, in eyes with primary angle closure disease (PACD). SETTING: Xiamen University Affiliated Xiamen Eye center, Xiamen, Fujian, China. DESIGN: Prospective case series. METHODS: Patients diagnosed with PACD and cataract and met the indication for cataract surgery were enrolled in the study. Six intraocular lens power calculation formulas were used to calculate refractive diopter. Percentage of eyes with prediction error (PE) within ±0.50D, and the median absolute prediction error (MedAE) were compared to determine the accuracy of different formulas in PACD patients. Subgroup analysis was performed according to axial length (AL). The accuracy of Barrett Universal Ⅱ was compared between PACD patients and age-related cataract patients. RESULTS: 105 patients (105 eyes) with PACD and 35 patients (35 eyes) with age-related cataract were enrolled in the study. Haigis, Kane and Barrett Universal Ⅱ formula achieved a comparable outcome and outperformed over the other three formulas in PACD patients. Subgroup analysis showed that the group with long AL has lower values of MedAE. PE was significantly positively correlated with AL and negatively correlated with relative lens position (RLP) when calculated use Barrett Universal Ⅱ and Kane. CONCLUSIONS: Haigis, Kane and Barrett Universal Ⅱ formula achieved a comparable outcome and outperformed over the other three formulas in PACD patients.

The association between ambient air pollution exposure and connective tissue sarcoma risk: a nested case-control study using a nationwide population-based database.

A nationwide population-based database was utilized in a nested case-control study to explore the association between ambient air pollution exposure and the likelihood of developing connective tissue sarcoma. The study examined 280 cases of connective tissue sarcoma diagnosed between 2000 and 2012. A random sample of 1120 control subjects was selected from a subpopulation of claim records without a connective tissue sarcoma diagnosis in a 1:4 ratio. The control subjects were selected based on similar characteristics as the connective tissue sarcoma patients, including gender, birth year, and the year of diagnosis of the case group with medical records. Risk factors for connective tissue sarcoma were collected for analysis. Our data on exposure to air pollutants was collected from Taiwan's Air Quality Monitoring Network, which has been gathering air quality data from a growing network of sampling stations (now 76) throughout the country since 1997. It was discovered that the risk of connective tissue sarcoma was significantly increased by the Charlson comorbidity index (CCI), elevated levels of specific air pollution indices (e.g., total hydrocarbons (THC), fine particulate matter (PM2.5), and O3_8 (the annual mean of the daily maximum 8-h average concentration of O3), the High Pollutant Standards Index (hPSI) (the percentage of days in a given year in Taiwan where the PSI exceeds 100), and an insurable monthly wage over US$1100. Further investigation is needed to explore the involvement of these air pollutants in the formation of connective tissue sarcoma.

C-Terminal Truncated HBx Facilitates Oncogenesis by Modulating Cell Cycle and Glucose Metabolism in FXR-Deficient Hepatocellular Carcinoma.

Farnesoid X receptor (FXR) is a nuclear receptor known to play protective roles in anti-hepatocarcinogenesis and regulation of the basal metabolism of glucose, lipids, and bile acids. FXR expression is low or absent in HBV-associated hepatocarcinogenesis. Full-length HBx and HBx C-terminal truncation are frequently found in clinical HCC samples and play distinct roles in hepatocarcinogenesis by interacting with FXR or FXR signaling. However, the impact of C-terminal truncated HBx on the progression of hepatocarcinogenesis in the absence of FXR is unclear. In this study, we found that one known FXR binding protein, a C-terminal truncated X protein (HBx C40) enhanced obviously and promoted tumor cell proliferation and migration by altering cell cycle distribution and inducing apoptosis in the absence of FXR. HBx C40 enhanced the growth of FXR-deficient tumors in vivo. In addition, RNA-sequencing analysis showed that HBx C40 overexpression could affect energy metabolism. Overexpressed HSPB8 aggravated the metabolic reprogramming induced by down-regulating glucose metabolism-associated hexokinase 2 genes in HBx C40-induced hepatocarcinogenesis. Overall, our study suggests that C-terminal truncated HBx C40 synergizes with FXR deficiency by altering cell cycle distribution as well as disturbing glucose metabolism to promote HCC development.

Tailoring and application of a multi-responsive cellulose nanofibre-based 3D nanonetwork wound dressing.

The rapid loss of drugs and the weak curative effects due to cyclical urination are the main reasons why wound heal with difficulty after bladder tumour resection. Here, a bioinspired cellulose nanofibre (CNF)-based magnetic 3D nanonetwork wound dressing with excellent tissue adhesion and biocompatibility is designed by the assembly of pH- and near infrared-responsive CNF nanoskeletons, magnetic switching Fe3O4 nanoparticles, and temperature switching Pluronic®F-127. The dressing with high loading capacity for mitomycin and indocyanine green can form a sticky 3D nanonetwork at the wound site and remain for a long time to release drugs through an external magnetic field. Interestingly, the dressing possessed excellent antibacterial activity, bacterial biofilm elimination, T24 tumour cell killing, and wound healing promotion through photothermal, photodynamic, and chemotherapy. Therefore, it has promising application for bladder postoperative infected wound healing to avoid rapid loss of drugs due to cyclical urination.

The impact of Teach-back method on preoperative anxiety and surgical cooperation in elderly patients undergoing outpatient ophthalmology surgery: A randomized clinical trial.

BACKGROUND: The literatures have demonstrated that Teach-back method is an effective communication tool to understand health education, especially in the elderly patients. However, there is limited research of Teach-back method in preoperative education for outpatient surgical patients. This study was conducted to investigate the effects of the Teach-back method on preoperative anxiety and surgical cooperation in elderly patients undergoing outpatient ophthalmology surgery. METHODS: One hundred sixteen elderly patients who underwent outpatient ophthalmology surgery were selected as the research objects. They were divided into the observation group (58 cases) and the control group (58 cases). The Teach-back preoperative education was adopted in the observation group and the standard preoperative education method was adopted in the control group. The degree of anxiety, surgical cooperation, and awareness of health knowledge were compared between the 2 groups, and the variations of blood pressure and heart rate, as well as the highest values of intraoperative blood pressure and heart rate before and after method, were recorded and compared. RESULTS: The preoperative systolic blood pressure in the observation group was significantly lower than that in the control group. The intraoperative (the highest value) heart rate, systolic blood pressure, and diastolic blood pressure in the observation group were lower than those in the control group, and the differences were statistically significant (P < .05). After intervention, the anxiety score and information demand score of the observation group were lower than those of the control group, and the differences were statistically significant (P < .05). The degree of surgery cooperation and awareness of perioperative health knowledge in the observation group were all higher than those in the control group; the differences were statistically significant (P < .05). CONCLUSION: The Teach-back method could relieve the preoperative anxiety of the patients, improve the quality of patients surgery cooperation, and facilitate the awareness of health knowledge. Moreover, it could effectively improve the intraoperative stress response of the elderly patients and reduce the large fluctuations of blood pressure and heart rate.

Marrow Mesenchymal Stem Cell-Derived Exosomes Upregulate Astrocytic Glutamate Transporter-1 Expression via miR-124/mTOR Pathway against Oxygen-Glucose Deprivation/Reperfusion Injury.

BACKGROUND: Experimental investigations have reported the efficacy of marrow mesenchymal stem cell-derived exosomes (MSC-Exos) for the treatment of ischemic stroke. The therapeutic mechanism, however, is still unknown. The purpose of the study is to show whether MSC-Exos increases astrocytic glutamate transporter-1 (GLT-1) expression in response to ischemic stroke and to investigate further mechanisms. METHODS AND RESULTS: An in vitro ischemia model (oxygen-glucose deprivation/reperfusion, OGD/R) was used. MSC-Exos was identified by Western blot (WB) and transmission electron microscopy (TEM). To further investigate the mechanism, MSC-Exos, miR-124 inhibitor, and mimics, and a mTOR pathway inhibitor (rapamycin, Rap) were used. The interaction between GLT-1 and miR-124 was analyzed by luciferase reporter assay. The GLT-1 RNA expression and miR-124 was assessed by quantitative real-time polymerase chain reaction (qRTPCR). The protein expressions of GLT-1, S6, and pS6 were detected by WB. Results demonstrated that MSC-Exos successfully inhibited the decrease of GLT-1 and miR-124 expression and the increase of pS6 expression in astrocytes after OGD/R. miR-124 inhibitor suppressed the effect of MSC-Exos on GLT-1 upregulation after OGD/R. Rapamycin notably decreased pS6 expression with significantly higher GLT-1 expression in astrocytes injured by OGD/R. Luciferase activity of the reporter harboring the wild-type or mutant GLT-1 3'UTR was not inhibited by miR-124 mimics. Further results showed that the inhibiting effect of MSC-Exos on pS6 expression and promoting effect of MSC-Exos on GLT-1 expression could be reversed by miR-124 inhibitor after OGD/R; meanwhile, the above conditions could be reversed again by rapamycin. CONCLUSIONS: Results show that miR-124 and the mTOR pathway are involved in regulation of MSC-Exos on GLT-1 expression in astrocytes injured by OGD/R. miR-124 does not directly target GLT-1. MSC-Exos upregulates GLT-1 expression via the miR-124/mTOR pathway in astrocytes injured by OGD/R.

Diagnosis and prognosis of breast cancer by high-performance serum metabolic fingerprints.

High-performance metabolic analysis is emerging in the diagnosis and prognosis of breast cancer (BrCa). Still, advanced tools are in demand to deliver the application potentials of metabolic analysis. Here, we used fast nanoparticle-enhanced laser desorption/ionization mass spectrometry (NPELDI-MS) to record serum metabolic fingerprints (SMFs) of BrCa in seconds, achieving high reproducibility and low consumption of direct serum detection without treatment. Subsequently, machine learning of SMFs generated by NPELDI-MS functioned as an efficient readout to distinguish BrCa from non-BrCa with an area under the curve of 0.948. Furthermore, a metabolic prognosis scoring system was constructed using SMFs with effective prediction performance toward BrCa (P < 0.005). Finally, we identified a biomarker panel of seven metabolites that were differentially enriched in BrCa serum and their related pathways. Together, our findings provide an efficient serum metabolic tool to characterize BrCa and highlight certain metabolic signatures as potential diagnostic and prognostic factors of diseases including but not limited to BrCa.

EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription.

TSPAN family of proteins are generally considered to assemble as multimeric complexes on the plasma membrane. Our previous work uncovered that TSPAN8 can translocate into the nucleus as a membrane-free form, a process that requires TSPAN8 palmitoylation and association with cholesterol to promote its extraction from the plasma membrane and subsequent binding with 14-3-3θ and importin-ß. However, what upstream signal(s) regulate(s) the nuclear translocation of TSPAN8, the potential function of TSPAN8 in the nucleus, and the underlying molecular mechanisms all remain unclear. Here, we demonstrate that, epidermal growth factor receptor (EGFR) signaling induces TSPAN8 nuclear translocation by activating the kinase AKT, which in turn directly phosphorylates TSPAN8 at Ser129, an event essential for its binding with 14-3-3θ and importin ß1. In the nucleus, phosphorylated TSPAN8 interacts with STAT3 to enhance its chromatin occupancy and therefore regulates transcription of downstream cancer-promoting genes, such as MYC, BCL2, MMP9, etc. The EGFR-AKT-TSPAN8-STAT3 axis was found to be hyperactivated in multiple human cancers, and associated with aggressive phenotype and dismal prognosis. We further developed a humanized monoclonal antibody hT8Ab4 that specifically recognizes the large extracellular loop of TSPAN8 (TSPAN8-LEL), thus being able to block the extraction of TSPAN8 from the plasma membrane and consequently its nuclear localization. Importantly, both in vitro and in vivo studies demonstrated an antitumor effect of hT8Ab4. Collectively, we discovered an unconventional function of TSPAN8 and dissected the underlying molecular mechanisms, which not only showcase a new layer of biological complexity of traditional membrane proteins, but also shed light on TSPAN8 as a novel therapeutic target for refractory cancers.

ERRα expression in ovarian cancer and promotes ovarian cancer cells migration in vitro.

PURPOSE: Ovarian cancer is the leading cause of death from a gynaecological malignancy in the developed world, and is characterized by invasion and metastasis and thus causes a high fatality rate. Estrogen-related receptor alpha (ERRα) has been demonstrated to play a widespread and pathophysiological relevant role in tumourigenesis and development. The aim of this study was to investigate the effect of ERRα expression on the progression of ovarian cancer. METHODS: The correlation between ERRα expression level and clinical pathological parameters in ovarian cancer tissues were analysed via cancer public database CPTAC. The expression level of ERRα in ovarian cancer cells were confirmed by RT-qPCR and Western blot methods. The cellular ERRα expression was up-regulated by lentivirus transfection and down-regulated by specific antagonist. The invasion and metastasis capabilities of ovarian cancer cells were characterized by wound healing assay and trans-well chamber assay. RESULTS: The CPTAC database showed that the ERRα expression levels were higher in the late-stage and high-grade ovarian cancer tissues than in early-stage and low-grade tissues. Ovarian cancer cells with higher-expression ERRα exhibited stronger invasion and metastasis capabilities in vitro. After up-regulating the ERRα expression level, the invasion and metastasis capabilities of ovarian cancer cells were enhanced, while down-regulation weakened. Moreover, the wound sealing rate was positively correlated with the expression of ERRα mRNA expression level (r = 0.921, P < 0.01), and the cell invasiveness was also positively correlated with the cellular ERRα mRNA expression level (r = 0.926, P < 0.01). CONCLUSIONS: Our results suggest that ERRα may promote the progression of ovarian cancer, and may serve as a promising predictive biomarker.

MicroRNA-mediated regulation of reactive astrocytes in central nervous system diseases.

Astrocytes (AST) are abundant glial cells in the human brain, accounting for approximately 20-50% percent of mammalian central nervous system (CNS) cells. They display essential functions necessary to sustain the physiological processes of the CNS, including maintaining neuronal structure, forming the blood-brain barrier, coordinating neuronal metabolism, maintaining the extracellular environment, regulating cerebral blood flow, stabilizing intercellular communication, participating in neurotransmitter synthesis, and defending against oxidative stress et al. During the pathological development of brain tumors, stroke, spinal cord injury (SCI), neurodegenerative diseases, and other neurological disorders, astrocytes undergo a series of highly heterogeneous changes, which are called reactive astrocytes, and mediate the corresponding pathophysiological process. However, the pathophysiological mechanisms of reactive astrocytes and their therapeutic relevance remain unclear. The microRNAs (miRNAs) are essential for cell differentiation, proliferation, and survival, which play a crucial role in the pathophysiological development of CNS diseases. In this review, we summarize the regulatory mechanism of miRNAs on reactive astrocytes in CNS diseases, which might provide a theoretical basis for the diagnosis and treatment of CNS diseases.

Bioinformatics Analysis of Expression Profiles and Prognostic Values of the Signal Transducer and Activator of Transcription Family Genes in Glioma.

Signal transducer and activator of transcription (STAT) family genes-of which there are seven members: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6-have been associated with the progression of multiple cancers. However, their prognostic values in glioma remain unclear. In this study, we systematically investigated the expression, the prognostic value, and the potential mechanism of the STAT family genes in glioma. The expression of STAT1/2/3/5A/6 members were significantly higher and positively correlated with IDH mutations, while the expression of STAT5B was lower and negatively correlated with IDH mutations in glioma. Survival analysis indicated that the upregulation of STAT1/2/3/5A/6 and downregulation of STAT5B expression was associated with poorer overall survival in glioma. Joint effects analysis of STAT1/2/3/5A/5B/6 expression suggested that the prognostic value of the group was more significant than that of each individual gene. Thus, we constructed a risk score model to predict the prognosis of glioma. The receiver operating characteristic curve and calibration curves showed good performance as prognostic indicators in both TCGA (The Cancer Genome Atlas) and the CGGA (Chinese Glioma Genome Atlas) databases. Furthermore, we analyzed the correlation between STAT expression with immune infiltration in glioma. The Protein-protein interaction network and enrichment analysis showed that STAT members and co-expressed genes mainly participated in signal transduction activity, Hepatitis B, the Jak-STAT signaling pathway, transcription factor activity, sequence-specific DNA binding, and the cytokine-mediated signaling pathway in glioma. In summary, our study analyzed the expression, prognostic values, and biological roles of the STAT gene family members in glioma, based on which we developed a new risk score model to predict the prognosis of glioma more precisely.

The best thickness of cornea graft from SMILE surgery as patch graft in glaucoma drainage implant surgery.

OBJECTIVE: The aim of this study was to determine the best thickness of corneal slices acquired from femtosecond laser surgery-small incision lenticule extraction (SMILE surgery) as patch graft in glaucoma drainage implantation surgery. METHODS: This study is a prospective randomized study. Patients who received glaucoma drainage implantation from September 2016 to November 2018 were observed. The patients were randomly divided into 3 groups. Group A included 102 cases (104 eyes), receiving 1 layer (120-150 µm) of allogeneic lamellar corneal tissue as the graft. Group B included 117 cases (120 eyes), receiving 2 layers of lamellar corneal tissue from one donor. Group C included 109 cases (111 eyes), using 3 layers of lamellar corneal tissue from 2 donors. The intraocular pressure, corneal graft, conjunctiva stromalysis, drainage tube exposure, and drainage plate were observed. RESULTS: Patients were followed up for 6 to 33 months. The intraocular pressure was significantly reduced after surgery in all three groups. Conjunctiva stromalysis and drainage tubes were exposed in 3 eyes (3%) in group A and 1 eye (0.8%, a special case which has nystagmus and the plate was placed infratemporally) in group B, whereas no conjunctiva stromalysis or tube exposure was reported in group C. CONCLUSIONS: The corneal graft acquired from SMILE surgery can effectively prevent drainage tube exposure and give patients a better cosmetic appearance. Two layers of lamellar corneal tissue (240-300 µm) may be the best suitable thickness because it can effectively reduce tube exposure and rejection. In some special cases, 3 layers of lamellar corneal tissue are needed.

Genetic diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum on Bioko Island, Equatorial Guinea and global comparative analysis.

BACKGROUND: Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. METHODS: 153 blood spot samples from Bioko malaria patients were collected during 2016-2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. RESULTS: A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN-dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. CONCLUSIONS: Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.

Estrogen receptor-associated receptor α and peroxisome proliferator-activated receptor γ in metabolism and disease (Review).

Estrogen receptor­associated receptor α (ERRα) is an orphan nuclear receptor that lacks corresponding ligands. ERRα recruits co­regulators to regulate gene transcription and plays an important role in human physiological functions. Peroxisome proliferator­activated receptor Î³ (PPARγ) is also a nuclear receptor that regulates the expression of target genes via a ligand­dependent mechanism, thereby participating in a series of physiological processes. Both ERRα and PPARγ are involved in the process of energy metabolism and tumorigenesis. In the present review, a concise overview of the important roles governed by ERRα and PPARγ in metabolism and their association with various disease are provided.

Partial abrogation of FXR-KNG1 signaling by carboxyl-terminal truncated HBx-C30 in hepatitis B virus-associated hepatocellular carcinoma.

Hepatitis B virus (HBV) X protein (HBx) is a key regulator of HBV-associated hepatocarcinogenesis. C-terminal-truncated HBx is frequently detected in hepatocellular carcinoma (HCC). The role of HBx, especially C-terminal-truncated HBx, in HCC pathogenesis has been controversial. To elucidate the biological role of C-terminal-truncated HBx underlying HBV-associated hepato-oncogenesis, we constructed a vector expressing HBx-C30 (deletion of 30 aa from the C terminus of HBx) and functionally analyzed its regulation on farnesoid X receptor (FXR) signaling, which is known to inhibit hepatocarcinogenesis. In the present study, we found full-length HBx and HBx C-terminal truncation coexist in HCC, and both full length HBx and HBx-C30 can activate FXR signaling. Moreover, HBx-C30 weakly coactivates FXR-KNG1 signaling compared to full-length HBx.

Transcriptomic identification of HBx-associated hub genes in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. Among the risk factors involved in liver carcinogenesis, hepatitis B virus (HBV) X protein (HBx) is considered to be a key regulator in hepatocarcinogenesis. Whether HBx promotes or protects against HCC remains controversial, therefore exploring new HBx-associated genes is still important. METHODS: HBx was overexpressed in HepG2, HepG2.2.15 and SMMC-7721 cell lines, primary mouse hepatocytes and livers of C57BL/6N mice. High-throughput RNA sequencing profiling of HepG2 cells with HBx overexpression and related differentially-expressed genes (DEGs), pathway enrichment analysis, protein-protein interaction networks (PPIs), overlapping analysis were conducted. In addition, Gene Expression Omnibus (GEO) and proteomic datasets of HBV-positive HCC datasets were used to verify the expression and prognosis of selected DEGs. Finally, we also evaluated the known oncogenic role of HBx by oncogenic array analysis. RESULTS: A total of 523 DEGs were obtained from HBx-overexpressing HepG2 cells. Twelve DEGs were identified and validated in cells transiently transfected with HBx and three datasets of HBV-positive HCC transcription profiles. In addition, using the Kaplan-Meier plotter database, the expression levels of the twelve different genes were further analyzed to predict patient outcomes. CONCLUSION: Among the 12 identified HBx-associated hub genes, HBV-positive HCC patients expressing ARG1 and TAT showed a good overall survival (OS) and relapse-free survival (RFS). Thus, ARG1 and TAT expression could be potential prognostic markers.

Dysregulation of hepatic microRNA expression in C57BL/6 mice affected by excretory-secretory products of Fasciola gigantica.

The excretory-secretory products released by the liver fluke Fasciola gigantica (FgESPs) play important roles in regulating the host immune response during the infection. Identification of hepatic miRNAs altered by FgESPs may improve our understanding of the pathogenesis of F. gigantica infection. In this study, we investigated the alterations in the hepatic microRNAs (miRNAs) in mice treated with FgESPs using high-throughput small RNA (sRNA) sequencing and bioinformatics analysis. The expression of seven miRNAs was confirmed by quantitative stem-loop reverse transcription quantitative PCR (qRT-PCR). A total of 1,313 miRNAs were identified in the liver of mice, and the differentially expressed (DE) miRNAs varied across the time lapsed post exposure to FgESPs. We identified 67, 154 and 53 dysregulated miRNAs at 1, 4 and 12 weeks post-exposure, respectively. 5 miRNAs (miR-126a-3p, miR-150-5p, miR-155-5p, miR-181a-5p and miR-362-3p) were commonly dysregulated at the three time points. We also found that most of the DE miRNAs were induced by FgESPs in the mouse liver after 4 weeks of exposure. These were subjected to Gene Ontology (GO) enrichment analysis, which showed that the predicted targets of the hepatic DE miRNAs of mice 4 weeks of FgESPs injection were enriched in GO terms, including cell membrane, ion binding, cellular communication, organelle and DNA damage. KEGG analysis indicated that the predicted targets of the most downregulated miRNAs were involved in 15 neural activity-related pathways, 6 digestion-related pathways, 20 immune response-related pathways and 17 cancer-related pathways. These data provide new insights into how FgESPs can dysregulate hepatic miRNAs, which play important roles in modulating several aspects of F. gigantica pathogenesis.

Role of MAPK activity in PD-L1 expression in hepatocellular carcinoma cells.

PURPOSE: This study was set out to explore the role of MAPK activity in programmed cell death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) cells. METHODS: The protein expression of PD-L1 was determined by immunofluorescence and immunohistochemistry, and the expression levels of PD-L1 and MAPK-related proteins were determined by flow cytometry and Western blotting. Meanwhile, the RNA transcription level of CD274 was determined by qRT-PCR. RESULTS: Interferon-γ (IFN-γ), epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) signaling pathways were associated with CD274 gene expression in HCC. Epidermal growth factor (EGF) or IFN-γ stimulation increased CD274 mRNA and PD-L1 protein levels in a representative HCC cell line group, further enhanced by EGF and IFN-γ stimulation. Inhibition of the MAPK pathway by EGFR inhibitors ositinib or MEK 1 and 2 inhibitors selumetinib prevented the up-regulation of CD274 mRNA and PD-L1 proteins and membranes induced by EGF and IFN-γ. IFN-γ increased the transcriptional activity of CD274, while MAPK signaling enhanced the stability of CD274 mRNA. CONCLUSION: MAPK pathway activity plays a key role in PD-L1 expression in EGF and IFNγ-induced HCC and may provide a target for improving the efficacy of immunotherapy.

The role of long noncoding RNA SNHG7 in human cancers (Review).

Long non-coding RNAs (lncRNAs) have been demonstrated to serve important roles in a variety of human tumor types. The lncRNA small nucleolar RNA host gene 7 (SNHG7) is associated with a variety of cancer types, such as esophageal cancer, breast cancer and gastric neoplasia. Based on previous studies that examined SNHG7 expression in tumors, it has become clear that SNHG7 modulates tumorigenesis and cancer progression by acting as a competing endogenous RNA. SNHG7 can sponge tumor-suppressive microRNAs and regulate downstream signaling pathways. In addition, overexpression of SNHG7 is associated with the clinical characteristics of patients with cancer by regulating cellular proliferation, invasion and metastasis and by inhibiting apoptosis via a variety of mechanisms of action. The function of SNHG7 in tumorigenesis and cancer progression indicates that it can potentially act as a novel therapeutic target or a diagnostic biomarker for cancer therapy or detection, respectively.