Chronic active Epstein-Barr virus infection with reinfection of SARS-CoV-2: a case report.

We describe the case of a 57-year-old male with jaundice, abdominal distension and fatigue. He was diagnosed as chronic active Epstein-Barr virus infection (CAEBV) due to intermittent elevated liver enzymes, hepatosplenomegaly and pancytopenia, with persistent positive of EBV biomarkers in blood and also positive in liver tissue. The patient was reinfected by SARS-CoV-2 within 2 months companied with CAEBV. The patient's second infection with SARS-CoV-2 led to the aggravated liver dysfunction with pneumonia and re-admission. After receiving symptomatic treatment, the patient showed significantly improvement of symptoms with partially restoration of liver function. After discharge, the patient's health status continued to deteriorate and eventually died. The instances of SARS-CoV-2 co-infection with the original chronic virus are not uncommon, but the exact mechanism of EBV and SARS-CoV-2 coinfection and the relationship between them are still unclear. Since co-infection of SARS-CoV-2 with original chronic virus might affect each other and lead disease aggravated and complicated, it is necessary to differentiate in the diagnosis of disease and it is important to be aware of the re-infection signs of SARS-CoV-2 in people with chronic virus infection diseases, as well as the risk of co-infection of SARS-CoV-2 with other viruses.

Cardiac complications caused by biliary diseases: A review of clinical manifestations, pathogenesis and treatment strategies of cholecardia syndrome.

Gallbladder and biliary diseases (GBDs) are one of the most common digestive diseases. The connections between GBDs and several organs other than the liver have gradually surfaced accompanied by the changes in people's diet structure and the continuous improvement of medical diagnosis technology. Among them, cholecardia syndrome that takes the heart as the important target of GBDs complications has been paid close attention. However, there are still no systematic report about its corresponding clinical manifestations and pathogenesis. This review summarized recent reported types of cholecardia syndrome and found that arrhythmia, myocardial injury, acute coronary syndrome and heart failure are common in the general population. Besides, the clinical diagnosis rate of intrahepatic cholestasis of pregnancy (ICP) and Alagille syndrome associated with gene mutation is also increasing. Accordingly, the underlying pathogenesis including abnormal secretion of bile acid, gene mutation, translocation and deletion (JAG1, NOTCH2, ABCG5/8 and CYP7A1), nerve reflex and autonomic neuropathy were further revealed. Finally, the potential treatment measures and clinical medication represented by ursodeoxycholic acid were summarized to provide assistance for clinical diagnosis and treatment.

Gene set analysis with graph-embedded kernel association test.

MOTIVATION: Kernel-based association test (KAT) has been a popular approach to evaluate the association of expressions of a gene set (e.g. pathway) with a phenotypic trait. KATs rely on kernel functions which capture the sample similarity across multiple features, to capture potential linear or non-linear relationship among features in a gene set. When calculating the kernel functions, no network graphical information about the features is considered. While genes in a functional group (e.g. a pathway) are not independent in general due to regulatory interactions, incorporating regulatory network (or graph) information can potentially increase the power of KAT. In this work, we propose a graph-embedded kernel association test, termed gKAT. gKAT incorporates prior pathway knowledge when constructing a kernel function into hypothesis testing. RESULTS: We apply a diffusion kernel to capture any graph structures in a gene set, then incorporate such information to build a kernel function for further association test. We illustrate the geometric meaning of the approach. Through extensive simulation studies, we show that the proposed gKAT algorithm can improve testing power compared to the one without considering graph structures. Application to a real dataset further demonstrate the utility of the method. AVAILABILITY AND IMPLEMENTATION: The R code used for the analysis can be accessed at https://github.com/JialinQu/gKAT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Identification of MET fusions as novel therapeutic targets sensitive to MET inhibitors in lung cancer.

INTRODUCTION: Alterations in the MET gene, including amplifications and exon 14 skipping mutations, have been identified as actionable oncogenic alterations. However, MET fusions are rarely detected in lung cancer, and their sensitivity to therapeutics has not been systematically analyzed. METHODS: The data from 30876 lung cancer patients from the LAVA database and 7966 patients from cBioPortal database were screened. Basic demographic and clinical information for the patients harboring MET fusions were collected. A lung squamous cell cancer patient harboring a novel EML4-MET fusion was treated with crizotinib. Additionally, a literature review was performed to summarize the cases of patients harboring MET fusions and their treatment information. RESULTS: MET fusions were found in only 0.2% to 0.3% of lung cancer patients and appeared in almost all exons of the MET gene. Intragenic MET fusions were found in 52.6% (41/78) of the included patients. Crizotinib was effective for MET fusions, including a novel identified EML4-MET fusion, even after the failure of multiple lines of treatment. This result suggested that acquired MET fusions become more regionally selective, as they usually occurred in exons encoding the extracellular region. Interestingly, the MET-fused genes in primary MET fusions or acquired MET fusions were very different, which indicated the different functions and influences of the disease. CONCLUSION: MET fusions are rare, and half of the fusion types were intragenic fusions. Lung cancer patients harboring primary or acquired MET fusions could benefit from crizotinib. In addition, EML4-MET was first reported in this study as a novel MET fusion type.

Characterization and clinical verification of immune-related genes in hepatocellular carcinoma to aid prognosis evaluation and immunotherapy.

BACKGROUND: Immune-related genes (IRGs) have been confirmed to play an important role in tumorigenesis and tumor microenvironment formation in hepatocellular carcinoma (HCC). We investigated how IRGs regulates the HCC immunophenotype and thus affects the prognosis and response to immunotherapy. METHODS: We investigated RNA expression of IRGs and developed an immune-related genes-based prognostic index (IRGPI) in HCC samples. Then, the influence of the IRGPI on the immune microenvironment was comprehensively analysed. RESULTS: According to IRGPI, HCC patients are divided into two immune subtypes. A high IRGPI was characterized by an increased tumor mutation burden (TMB) and a poor prognosis. More CD8 + tumor infiltrating cells and expression of PD-L1 were observed in low IRGPI subtypes. Two immunotherapy cohorts confirmed patients with low IRGPI demonstrated significant therapeutic benefits. Multiplex immunofluorescence staining determined that there were more CD8 + T cells infiltrating into tumor microenvironment in IRGPI-low groups, and the survival time of these patients was longer. CONCLUSIONS: This study demonstrated that the IRGPI serve as a predictive prognostic biomarker and potential indicator for immunotherapy.

Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification.

BACKGROUND: N6-methyladenine (m6A) is the most common modification of mRNA and IncRNA in higher organisms. m6A has been confirmed to be related to the formation and progression of tumors and m6A-related genes can be used as prognostic biomarkers in a variety of tumors. However, there have been no similar studies on lung squamous cell carcinoma. The main purpose of this study was aimed to explore the differential expression of m6A-related genes in lung squamous cell carcinoma tissues and its relationship with patient clinical prognosis. METHODS: We integrated three m6A writers that catalyze the methylation of adenine on mRNA molecules. The training set including 501 patients with LUSC was collected from The Cancer Genome Atlas (TCGA) database and the test set including 181 patients with LUSC was collected from the Gene Expression Omnibus (GEO) database. Based on the expression level of the m6A methylase gene, we established a tumor subgroup and risk-prognosis model to quantify the risk index and long-term patient prognosis, which were confirmed by principal component analysis (PCA) and receiver operating characteristic (ROC) curve analysis. After lung squamous cell carcinoma tissue specimens were obtained during surgery, immunohistochemistry (IHC) was used to verify the results in vitro. RESULTS: The results of the study showed that the expression of the three m6A methylases in tumor tissues and normal tissues was significantly different (P < 0.05). The survival-prognostic model based on METTL3 gene expression showed better predictive performance (AUC: 0.706). Patients in the high-risk and low-risk groups exhibited significant differences in terms of survival time and 5-year and 10-year survival rates. Immunohistochemistry revealed that patients with high METTL3 expression exhibited a longer survival time than those with low METTL3 expression. CONCLUSIONS: Our study showed that the molecular phenotype based on the expression of METTL3 may be an independent risk factor affecting the prognosis of lung squamous cell carcinoma. These findings not only prove the important role of m6A methylase in lung squamous cell carcinoma, but are also expected to provide more accurate prognostic assessment and individualized treatment for patients with lung squamous cell carcinoma.

The pathogenesis of renal injury in obstructive jaundice: A review of underlying mechanisms, inducible agents and therapeutic strategies.

Kidney injury is one of the main complications of obstructive jaundice (OJ) and its pathogenesis has not been clarified. As an independent risk factor for OJ associated with significant morbidity and mortality, it can be mainly divided into two types of morphological injury and functional injury. We called these dysfunctions caused by OJ-induced kidney injury as OJKI. However, the etiology of OJKI is still not fully clear, and research studies on how OJKI becomes a facilitated factor of OJ are limited. This article reviews the underlying pathological mechanism from five aspects, including metabolisms of bile acids, hemodynamic disturbances, oxidative stress, inflammation and the organic transporter system. Some nephrotoxic drugs and measures that can enhance or reduce the renal function with potential intervention in perioperative periods to alleviate the incidence of OJKI were also described. Furthermore, a more in-depth study on the pathogenesis of OJKI from multiple aspects for exploring more targeted treatment measures were further put forward, which may provide new methods for the prevention and treatment of clinical OJKI and improve the prognosis.

Identification of an RNA binding protein-related gene signature in hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant primary cancer with high mortality. Previous studies have demonstrated that RNA binding proteins (RBPs) are involved in the biological processes of cancers, including hepatocellular cancer. METHODS: In this study, we aimed to identify the clinical value of RNA-binding proteins for hepatocellular carcinoma. We obtained gene expression and clinical data of hepatocellular carcinoma patients from the TCGA and ICGC databases. The prognostic value of RBP-related genes in patients with hepatocellular carcinoma and their function were studied by comprehensive bioinformatics analyses. The gene signature of SMG5, EZH2, FBLL1, ZNF239, and IGF2BP3 was generated by univariate and multivariate Cox regression and LASSO regression analyses. We built and verified a prognostic nomogram based on RBP-related genes. The gene signature was validated by the ICGC database. The expression of RBP-related genes was validated by the Oncomine database, the Human Protein Atlas and Kaplan-Meier plotter. RESULT: Most RBP-related genes were significantly different in cancer and normal tissues. The survival of patients in the different groups was significantly different. The gene signature showed good performance for predicting the survival of HCC patients by having a better area under the receiver operating characteristic curve than other clinicopathological parameters. CONCLUSION: Gene signatures based on RNA-binding proteins can be independent risk factors for hepatocellular carcinoma patients.

A novel open-tubular capillary electrochromatography using carboxymethyl-ß-cyclodextrin functionalized gold nanoparticles as chiral stationary phase.

Enantioselective open tubular capillary electrochromatography with carboxymethyl-ß-cyclodextrin conjugated gold nanoparticles as stationary phase was developed. This novel open tubular column was fabricated through layer-by-layer self-assembly of gold nanoparticles on a 3-mercaptopropyl-trimethoxysilane-modified fused-silica capillary and subsequent surface functionalization of the gold nanoparticles through self-assembly of 6-mercapto-ß-cyclodextrin. The 6-mercapto-ß-cyclodextrin was firstly synthesized and determined by extensive spectroscopic data. Scanning electron microscopy, energy dispersive X-ray analysis spectroscopy, and electroosmotic flow experiments were carried out to characterize the prepared open tubular column. Then, the separation effectiveness of the open tubular column was verified by two pairs of ɑ-tetralones derivatives enantiomers and two pairs of basic drug enantiomers (tramadol hydrochloride and zopiclone) as mode analytes. Factors that influence the enantioseparation were optimized, and under the optimized conditions, satisfactory separation results were obtained for the four enantiomers: compound A, compound B, tramadol hydrochloride, and zopiclone with resolutions of 3.79, 1.56, 1.03, 1.60, respectively. For the combination of gold nanoparticles and negatively charged carboxymethyl-ß-cyclodextrin, the open tubular column exhibited wider separation range for neutral and basic drugs. Moreover, the repeatability and stability of the column were studied through the run-to-run and day-to-day investigations.

Sol-gel technique for the preparation of ß-cyclodextrin gold nanoparticles as chiral stationary phase in open-tubular capillary electrochromatography.

A novel open-tubular capillary electrochromatography column coated with ß-cyclodextrin was prepared using the sol-gel technique. In the sol-gel approach, owing to the three-dimensional network of sol-gel and the strong chemical bond between the stationary phase and the surface of capillary columns, good chromatographic characteristics and unique selectivity in separating enantiomers were shown. The influences of capillary inner diameter, coating time, organic modifier, buffer pH, and buffer concentration on separation were investigated. The sol-gel-coated ß-cyclodextrin column has shown improved enantioseparation efficiency of chlorphenamine, brompheniramine, pheniramine, zopiclone in comparison with the sol-gel matrix capillary column. The migration time relative standard deviation of the separation of the enantiomers was less than 0.89% over five runs and 2.9% from column to column. This work confirmed that gold nanoparticles are promising electrochromatographic support to enhance the phase ratio of open-tubular capillary electrochromatography column in capillary electrochromatography.

Lactobacillus rhamnosus GG microcapsules inhibit Escherichia coli biofilm formation in coculture.

OBJECTIVES: Microbial biofilms have become one of the most significant causes of nosocomial infections. The aim of this study was to examine the potential quorum sensing inhibitor activities of Lactobacillus rhamnosus GG microcapsules. RESULTS: Lactobacillus rhamnosus GG microcapsules effectively inhibited initial biofilm formation at a concentration of 2.5 × 108 CFU/mL. Furthermore, the inhibition rate was increased to 79% in the Lactobacillus rhamnosus GG microcapsules group, resulting in a reduction in the biofilm maturation stage. In addition, real-time PCR analysis revealed that the LGG microcapsules can act as effective inhibitors of transcriptional activators of the quorum sensing circuit in E.coli, luxS, lsrK, and lsrR. CONCLUSIONS: Lactobacillus rhamnosus GG microcapsules can effectively inhibit biofilm formation and disturb mature biofilms.

Identification of metabolites in human and rat urine after oral administration of Xiao-Qing-Long-Tang granule using ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry.

Xiao-Qing-Long-Tang is a traditional Chinese formula used for the treatment of cold syndrome, bronchitis, and nasal allergies for thousands of years. However, the in vivo integrated metabolism of its multiple components and the active chemical constituents of Xiao-Qing-Long-Tang remain unknown. In this study, a method using ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was established for the detection and identification of the metabolites in human and rat urine after oral administration of Xiao-Qing-Long-Tang. A total of 19 compounds were detected or tentatively identified in human urine samples, including eight prototypes and 11 metabolites. Also, a total of 50 compounds were detected or tentatively identified in rat urine samples, including 15 prototypes and 35 metabolites detected with either a highly sensitive extracted ion chromatogram method or the MSE determination using Mass Fragment software. Our results indicated that phase Ⅱ reactions (e.g. glucuronidation and sulfation) were the main metabolic pathways of flavones, while phase I reactions (e.g. demethylation and hydroxylation) were the major metabolic reaction for alkaloids, lignans, and ginger essential oil. This investigation provided important structural information on the metabolism of Xiao-Qing-Long-Tang and provided evidence to obtain a more comprehensive metabolic profile.

Two new phenolic acids from the fruits of Forsythia suspense.

Two new phenolic acids forsythiayanoside C (1) and forsythiayanoside D (2), were isolated from the fruits of Forsythia suspense (Thunb.) Vahl. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses, HRESIMS and CD spectrometry. The cytotoxic and antioxidant activities testing showed that compound 2 exhibited free radical scavenging activity.

Molecular subtypes of disulfidptosis-regulated genes and prognosis models for predicting prognosis, tumor microenvironment infiltration, and therapeutic response in hepatocellular carcinoma.

Disulfidptosis, a recently identified mode of cellular demise marked by excess SLC7A11-reliant cystine, has been proved to affect the development and resilience of tumor cells through the production of glutathione from cystine. Glutathione synthesis plays a crucial role in chemotherapy resistance and the survival of liver cancer cells. Thus, understanding the relationship between disulfidptosis and hepatocellular carcinoma (HCC) is imperative. A molecular typing approach was employed to classify patients with HCC into two distinct subtypes, namely disulfidptosis and disulfide-homeostasis, based on the expression of genes associated with disulfidptosis. Patients with disulfidptosis exhibited a longer survival time, improved immune status, and heightened sensitivity to conventional chemotherapeutic drugs and immunotherapy. Patients with disulfide-homeostasis demonstrated an immunosuppressive microenvironment, drug resistance, and unfavorable prognosis. A prognostic model was constructed utilizing the significant prognostic variables of the disulfidptosis-regulated genes. A real-world cohort was subjected to multiplex immunofluorescence to validate the clinical outcomes and immune context. Ultimately, our study delved into the prognostic relevance of disulfidptosis in HCC and provides insights into potential avenues for future research.

Hypoglycemic activity of immature persimmon (Diospyros kaki Thunb.) extracts and its inhibition mechanism for α-amylase and α-glucosidase.

Persimmon tannins, particularly in immature persimmons, haven't yet received corresponding attention to research on therapy of diabetes mellitus in spite of high hypoglycemic activity. To accurately screening key hypoglycemic components, immature persimmon extracts were isolated and identified using enzyme affinity ultrafiltration and HRLC-ESI-MS/MS. Among them, Hederagenin (IC50 = 0.077 ± 0.003 mg/mL), Ursolic acid (IC50 = 0.001 ± 0.000 mg/mL) and Quercetin dehydrate (IC50 = 0.081 ± 0.001 mg/mL) exhibited the strongest inhibitory effect on α-amylase (HSA and PPA) and α-glucosidase, respectively. And their inhibition mechanisms were analyzed using multi-spectral analysis, atomic force microscope and molecular docking, indicating the bonding with starch digestion enzymes through hydrogen bonding and hydrophobic interaction, and generating the enzyme aggregation. In vivo starch-tolerance experiment further verified that these inhibitors could improve postprandial hyperglycemia (17.18 % âˆ¼ 40.29 %), far more than acarbose. Suppressing, Hederagenin and Ursolic acid as triterpenoids appeared amazing potentiality to alleviate postprandial hyperglycemia, which suggested that IPE were comprehensive exploration values on prevention and treatment of hyperglycemia.

The analysis of multiple omics and examination of pathological images revealed the prognostic and therapeutic significances of CD93 in lung squamous cell carcinoma.

As a potent pro-angiogenic factor, the role of CD93 in the prognosis and therapeutic outcomes of lung squamous cell carcinoma (LUSC) merits exploration. In this study, we systematically collected transcriptomic, genomic, and clinical data from various public databases, as well as pathological images from hospital-operated patients. Employing statistical analysis software like R (Version 4.2.2) and GraphPad (Version 8.0), we conducted comprehensive analyses of multi-omics data. The results revealed elevated CD93 expression in LUSC tissues, closely associated with various cancer-related pathways. High CD93 expression indicated advanced clinical stage and poorer prognosis. Furthermore, CD93 contributed to resistance against chemotherapy and immunotherapy by enhancing tumor cell stemness, reducing immune cell infiltration, and inducing T cell exhaustion. Patients with low CD93 expression exhibited higher response rates to both chemotherapy and immunotherapy. Immunohistochemistry validated the significance of CD93 in LUSC. CD93 emerges as a biomarker signaling unfavorable prognosis and influencing therapeutic outcomes, suggesting a potential LUSC treatment avenue.

Integrated pharmacokinetic properties and tissue distribution of multiple active constituents in Qing-Yi Recipe: A comparison between granules and decoction.

BACKGROUND: Qing-Yi Recipe, a classic traditional Chinese medicine (TCM), is widely used for treating acute diseases of the abdomen, especially pancreatitis, the efficacy of which has been demonstrated in more than thirty clinical trials. However, the in-vivo pharmacodynamic material basis for this formula remains unclear. METHODS: A sensitive and accurate method for quantifying twenty-two potential bioactive constituents of Qing-Yi Recipe in biological samples was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this method was fully validated. Then, the integrated pharmacokinetic properties of Qing-Yi Recipe and its major metabolites in rats were investigated using the post-listed granules at both dosages. Subsequently, tissue distributions of those constituents in nine organs (especially the pancreas) were determined, and the overall parameters between the two formulations were compared. RESULTS: Though the chemical profiles of the formulas varied across formulations, the overall exposure level was very similar, and baicalin, wogonoside, geniposide, rhein, costunolide, and paeoniflorin were the top six bioactive compounds in the circulation. All twenty-two natural products reached their first peak within 2 h, and several of them exhibited bimodal or multimodal patterns under the complicated transformation of metabolic enzymes, and the parameters of these products markedly changed compared with those of monomers. Diverse metabolites of emodin and baicalin/baicalein were detected in circulation and tissues, augmenting the in vivo forms of these compounds. Finally, the enrichment of tetrahydropalmatine and corydaline in the pancreas were observed and most compounds remained in the gastrointestinal system, providing a foundation basis for their potential regulatory effects on the gut microbiota as well as the intestinal functions. CONCLUSION: Herein, the pharmacokinetic properties and tissue distribution of multiple potential active constituents in Qing-Yi Recipe were investigated at two dosages, providing a pharmacodynamic material basis of Qing-Yi Recipe for the first time. This investigation is expected to provide a new perspective and reference for future studies on the physiological disposition and potential pharmacodynamic basis of traditional Chinese medicine to treat acute abdomen diseases.

Immature persimmon residue as a novel biosorbent for efficient removal of Pb(II) and Cr(VI) from wastewater: Performance and mechanisms.

Owing to the powerful affinity of tannin toward heavy metal ions, it is frequently immobilized on adsorbents to enhance their adsorption properties. However, natural adsorbents containing tannin have been overlooked owing to its water solubility. Herein, a novel natural adsorbent based on the immature persimmon residue (IPR) with soluble tannin removed was fabricated to eliminate Pb(II) and Cr(VI) in aquatic environments. The insoluble tannin in IPR endowed it with prosperous properties for eliminating Pb(II) and Cr(VI), and the IPR achieved maximum Pb(II) and Cr(VI) adsorption quantities of 68.79 mg/g and 139.40 mg/g, respectively. Kinetics and isothermal adsorption analysis demonstrated that the removal behavior was controlled by monolayer chemical adsorption. Moreover, the IPR exhibited satisfactory Pb(II) and Cr(VI) removal efficiencies even in the presence of multiple coexisting ions and showed promising regeneration potential after undergoing five consecutive cycles. Additionally, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) analysis unveiled that the elimination mechanisms were primarily electrostatic attraction, chelation and reduction. Overall, the IPR, as a tannin-containing biosorbent, was verified to possess substantial potential for heavy metal removal, which can provide new insights into the development of novel natural adsorbents from the perspective of waste resource utilization.

Exploring the chemical components of Kuanchang-Shu granule and its protective effects of postoperative ileus in rats by regulating AKT/HSP90AA1/eNOS pathway.

BACKGROUND: Postoperative ileus (POI) is a common obstruction of intestinal content passage caused by almost all abdominal operations that seriously strokes the quality of life of patients. Kuanchang-Shu granule (KCSG), a classic modified prescription based on "Da-Cheng-Qi Decoction", has obtained satisfactory efficacy in the clinical therapeutics of POI. However, its material basis and holistic molecular mechanism against POI have not been revealed. METHODS: The chemical ingredients of KCSG were first characterized by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Subsequently, an integration strategy of the network pharmacology and molecular docking based on above identified ingredients was performed to unveil the potential targets involved in the treatment of KCSG on POI. Finally, intestinal manipulation induced rat POI model was constructed to verify the efficacy and predicted mechanism of KCSG against POI. RESULTS: In total, 246 ingredients mainly including organic acids, flavonoids, quinones, alkaloids, terpenoids, phenylpropanoids and phenols were identified. 41 essential ingredients, 24 crucial targets as well as 15 relevant signaling pathways were acquired based on network pharmacology analysis. Pharmacodynamic research showed that KCSG treatment could protect intestinal histological damage, promote the recovery of measurement of gastrointestinal transit disorder and inhibit the secretion of myeloperoxidase in the distal ileum tissues. The up-regulated expression of p-AKT and down-regulated expression of p-eNOS and HSP9OAA1 predicted by molecular docking and validated by western blotting showed that AKT/eNOS/HSP90AA1 pathway may be one of the crucial mechanisms that mediates the protective effect of KCSG.

HBx and HBs regulate RhoC expression by upregulating transcription factor Ets-1.

The available evidence suggests that HBV proteins play an important role in the development of hepatocellular carcinoma (HCC). RhoC, a member of the Rho subfamily of the Ras superfamily of homologous genes, had been implicated in tumorigenesis and tumor progression. In a previous study, we demonstrated that HBx and HBs could up-regulate RhoC expression by enhancing its promoter activity. However, the specific mechanisms remain unclear. Here, we demonstrate that overexpression of Ets-1 results in upregulation of RhoC promoter activity and mRNA and protein levels. Expression of transcription factor Ets-1 was significantly higher in HepG2.2.15 cells than that in HepG2 cells. Meanwhile, infection of HepG2 cells with an HBV-adenovirus recombinant virus led to up-regulation of Ets-1. Of the four HBV proteins, HBx and HBs, could increase expression of Ets-1, which consequently contributed to the upregulation of RhoC. These findings might provide a novel insight into HBV-induced HCC metastasis.