Publications by authors named "Zhiliang Gao"

98 Publications

Encapsulation of Enzymes in Metal-Phenolic Network Capsules for the Trigger of Intracellular Cascade Reactions.

Langmuir 2021 Sep 13. Epub 2021 Sep 13.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, Shandong, China.

Nanoengineered capsules encapsulated with functional cargos (e.g., enzymes) are of interest for various applications including catalysis, bioreactions, sensing, and drug delivery. Herein, we report a facile strategy to engineer enzyme-encapsulated metal-phenolic network (MPN) capsules using enzyme-loaded zeolitic imidazolate framework nanoparticles (ZIF-8 NPs) as templates, which can be removed in a mild condition (e.g., ethylenediaminetetraacetic acid (EDTA) solution). The capsule size (from 250 nm to 1 μm) and thickness (from 9.8 to 33.7 nm) are well controlled via varying the template size and coating time, respectively. Importantly, MPN capsules encapsulated with enzymes (i.e., glucose oxidase) can trigger the intracellular cascade reaction via the exhaustion of glucose to produce HO and subsequently generate toxic hydroxyl radicals (OH) based on the Fenton reaction via the reaction between HO and iron ions in MPN coatings. The intracellular cascade reaction for the generation of OH is efficient to inhibit cancer cell viability, which is promising for the application in chemodynamic therapy.
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http://dx.doi.org/10.1021/acs.langmuir.1c01821DOI Listing
September 2021

Serum from Acute-on-chronic Liver Failure Patients May Affect Mesenchymal Stem Cells Transplantation by Impairing the Immunosuppressive Function of Cells.

J Clin Transl Hepatol 2021 Aug 30;9(4):503-513. Epub 2021 Mar 30.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Background And Aims: The safety and efficacy of mesenchymal stem cells (MSCs) in the treatment of acute-on-chronic liver failure (ACLF) have been validated. However, the impact of the pathological ACLF microenvironment on MSCs is less well understood. This study was designed to explore the changes in the functional properties of MSCs exposed to ACLF serum.

Methods: MSCs were cultured in the presence of 10%, 30% and 50% serum concentrations from ACLF patients and healthy volunteers. Then, the cell morphology, phenotype, apoptosis and proliferation of MSCs were evaluated, including the immunosuppressive effects. Subsequently, mRNA sequencing analysis was used to identify the molecules and pathways involved in MSC functional changes in the context of ACLF.

Results: In the presence of ACLF serum, MSC morphology significantly changed but phenotype did not. Besides, MSC proliferation activity was weakened, while the apoptosis rate was lightly increased. Most importantly, the immunosuppressive function of MSCs was enhanced in a low-concentration serum environment but transformed into a proinflammatory response in a high-concentration serum environment. RNA sequencing indicated that 10% serum concentration from ACLF patients mediated the PI3K-Akt pathway to enhance the anti-inflammatory effect of MSCs, while the 50% serum concentration from ACLF patients promoted the conversion of MSCs into a proinflammatory function by affecting the cell cycle.

Conclusions: The 50% ACLF serum concentration is more similar to the environment in the human body, which means that direct peripheral blood intravenous infusion of MSCs may reduce the effect of transplantation. Combining treatments of plasma exchange to reduce harmful substances in serum may promote MSCs to exert a stronger anti-inflammatory effect.
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http://dx.doi.org/10.14218/JCTH.2021.00014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369013PMC
August 2021

Sono-Fenton Chemistry Converts Phenol and Phenyl Derivatives into Polyphenols for Engineering Surface Coatings.

Angew Chem Int Ed Engl 2021 09 25;60(39):21529-21535. Epub 2021 Aug 25.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong, 250100, China.

We report a sono-Fenton strategy to mediate the supramolecular assembly of metal-phenolic networks (MPNs) as substrate-independent coatings using phenol and phenyl derivatives as building blocks. The assembly process is initiated from the generation of hydroxyl radicals ( OH) using high-frequency ultrasound (412 kHz), while the metal ions synergistically participate in the production of additional OH for hydroxylation/phenolation of phenol and phenyl derivatives via the Fenton reaction and also coordinate with the phenolic compounds for film formation. The coating strategy is applicable to various phenol and phenyl derivatives and different metal ions including Fe , Fe , Cu , and Co . In addition, the sono-Fenton strategy allows real-time control over the assembly process by turning the high-frequency ultrasound on or off. The properties of the building blocks are maintained in the formed films. This work provides an environmentally friendly and controllable method to expand the application of phenolic coatings for surface engineering.
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http://dx.doi.org/10.1002/anie.202108462DOI Listing
September 2021

Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy.

Aliment Pharmacol Ther 2021 08 22;54(3):329-338. Epub 2021 Jun 22.

Guangzhou, China.

Background: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB).

Aim: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy.

Methods: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body-mass index (BMI). Central obesity was evaluated by waist circumference, waist-to-hip ratio and waist-to-height ratio.

Results: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5-year cumulative incidence of HCC was 2.9%. Waist-to-height ratio performed better in predicting HCC development than BMI, waist circumference or waist-to-hip ratio. Patients with central obesity (defined as waist-to-height ratio >0.5) had significantly higher 5-year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist-to-height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12-3.13, P = 0.017).

Conclusions: Central obesity, evaluated by the waist-to-height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.
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http://dx.doi.org/10.1111/apt.16469DOI Listing
August 2021

Association between the nasopharyngeal microbiome and metabolome in patients with COVID-19.

Synth Syst Biotechnol 2021 Sep 14;6(3):135-143. Epub 2021 Jun 14.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, China.

SARS-CoV-2, the causative agent for COVID-19, infect human mainly via respiratory tract, which is heavily inhabited by local microbiota. However, the interaction between SARS-CoV-2 and nasopharyngeal microbiota, and the association with metabolome has not been well characterized. Here, metabolomic analysis of blood, urine, and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients, and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19. Results showed lactic acid, l-proline, and chlorogenic acid methyl ester (CME) were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones. Nasopharyngeal commensal bacteria including , and were notably depleted in the pharynges of COVID-19 patients, while , , and were relatively increased. The abundance of and were significantly positively associated with serum CME, which might be an anti-SARS-CoV-2 bacterial metabolite. This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility. The findings were based on a very limited number of patients enrolled in this study; a larger size of cohort will be appreciated for further investigation.
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http://dx.doi.org/10.1016/j.synbio.2021.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200311PMC
September 2021

Potential Networks Regulated by MSCs in Acute-On-Chronic Liver Failure: Exosomal miRNAs and Intracellular Target Genes.

Front Genet 2021 23;12:650536. Epub 2021 Apr 23.

Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Acute-on-chronic liver failure (ACLF) is a severe syndrome associated with high mortality. Alterations in the liver microenvironment are one of the vital causes of immune damage and liver dysfunction. Human bone marrow mesenchymal stem cells (hBMSCs) have been reported to alleviate liver injury via exosome-mediated signaling; of note, miRNAs are one of the most important cargoes in exosomes. Importantly, the miRNAs within exosomes in the hepatic microenvironment may mediate the mesenchymal stem cell (MSC)-derived regulation of liver function. This study investigated the hepatocyte exosomal miRNAs which are regulated by MSCs and the target genes which have potential in the treatment of liver failure. Briefly, ACLF was induced in mice using carbon tetrachloride and primary hepatocytes were isolated and co-cultured (or not) with MSCs under serum-free conditions. Exosomes were then collected, and the expression of exosomal miRNAs was assessed using next-generation sequencing; a comparison was performed between liver cells from healthy ACLF animals. Additionally, to identify the intracellular targets of exosomal miRNAs in humans, we focused on previously published data, i.e., microarray data and mass spectrometry data in liver samples from ACLF patients. The biological functions and signaling pathways associated with differentially expressed genes were predicted using gene ontology and Kyoto Encyclopedia of Genes and Genomics enrichment analyses; hub genes were also screened based on pathway analysis and the prediction of protein-protein interaction networks. Finally, we constructed the hub gene-miRNA network and performed correlation analysis and qPCR validation. Importantly, our data revealed that MSCs could regulate the miRNA content within exosomes in the hepatic microenvironment. MiR-20a-5p was down-regulated in ACLF hepatocytes and their exosomes, while the levels of chemokine C-X-C Motif Chemokine Ligand 8 (CXCL8; interleukin 8) were increased in hepatocytes. Importantly, co-culture with hBMSCs resulted in up-regulated expression of miR-20a-5p in exosomes and hepatocytes, and down-regulated expression of CXCL8 in hepatocytes. Altogether, our data suggest that the exosomal miR-20a-5p/intracellular CXCL8 axis may play an important role in the reduction of liver inflammation in ACLF in the context of MSC-based therapies and highlights CXCL8 as a potential target for alleviating liver injury.
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http://dx.doi.org/10.3389/fgene.2021.650536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102832PMC
April 2021

Ultrasound expands the versatility of polydopamine coatings.

Ultrason Sonochem 2021 Jun 21;74:105571. Epub 2021 Apr 21.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China; State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China. Electronic address:

Polydopamine (PDA) coating of surfaces is a versatile strategy to fabricate functional films on various substrates, which typically requires oxygen and alkaline pH. Overcoming such limitations may enhance the versatility of this technique. Herein, we develop a simple and green sonochemical process for PDA coatings, which overcomes the limitations of traditional coating technique and expands the versatility of PDA chemistry. The oxidizing radicals generated by high frequency ultrasound (412 kHz) are utilized to initiate and accelerate the polymerization of dopamine. The sonochemical rate of film deposition is found to be about twice faster than that of the traditional method in the presence of oxygen. Importantly, the PDA coatings can be obtained in neutral or acidic aqueous solutions and even in the absence of oxygen. The PDA coatings can be moderated by turning on or off high frequency ultrasound. This study provides an environmentally friendly and economic method for the engineering of PDA coatings independent of the solution pH and nature of dissolved gas.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100621PMC
June 2021

Correction to: Forkhead box (FOX) G1 promotes hepatocellular carcinoma epithelial-Mesenchymal transition by activating Wnt signal through forming T-cell factor-4/Betacatenin/FOXG1 complex.

J Exp Clin Cancer Res 2021 Mar 17;40(1):104. Epub 2021 Mar 17.

Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, 510630, Guangdong Province, China.

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http://dx.doi.org/10.1186/s13046-021-01900-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972186PMC
March 2021

Efficacy of 104-week Telbivudine-based optimization strategy in patients with HBeAg-negative chronic hepatitis B virus infections.

BMC Infect Dis 2020 Dec 7;20(1):931. Epub 2020 Dec 7.

Department of Infectious Disease, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong Province, China.

Background: Evaluate the safety and efficacy of 104-week regimen of Telbivudine(LdT)-based optimization strategy for Chinese patients who have chronic hepatits B(CHB) with HBeAg-negative.

Methods: This multi-center, open-label, prospective study enrolled 108 HBeAg-negative CHB patients who received LdT (600 mg/day) for 24 weeks, Adefovir (ADV) was added if HBV DNA remained detectable at week 24, otherwise LdT was maintained to use until 104 weeks. HBV DNA, alanine amino transferase (ALT), hepatitis B surface antigen(HBsAg), creatinine kinase(CK), and estimated glomerular filtration rate (eGFR) were measured, safety was assessed.

Results: Eighty-eight patients (81%) had HBV-DNA undetectable at 24 weeks and maintained to receive LdT monotherapy until 104 weeks, whereas the other 20 patients had HBV-DNA detectable and ADV was used in combination. For all patients, 72% of patients reached ALT normalization at 24 weeks, which increased to 80% at 52 weeks and 104 weeks, respectively.. 81% of total patients had undetectable HBV-DNA at 24 weeks, 92% at 52 weeks, and 94% at 104 weeks. The HBsAg titre declined steadily from baseline to 104 weeks (3.62 vs. 2.98 log10 IU/mL, p < 0.05), and the eGFR increased steadily from baseline to 104 weeks (92.9 vs. 104.4 mL/min/1.73 m, p < 0.05). Although 79 patients (73%) had at least one time of elevated CK, most of these patients had CK elevated in Grade 1/2.

Conclusions: LdT was well tolerated and effective, and 94% of patients achieved virological suppression after 104 weeks.

Trial Registration: This study was registered in clinicaltrials.gov on January 31, 2012 and the ID No. was NCT01521975 .
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http://dx.doi.org/10.1186/s12879-020-05642-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720458PMC
December 2020

Polypeptide Nanoparticles with pH-Sheddable PEGylation for Improved Drug Delivery.

Langmuir 2020 11 5;36(45):13656-13662. Epub 2020 Nov 5.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.

The variation of tumor microenvironments provides a tool for the construction of stimulus-responsive nanomedicines to enhance drug delivery efficacy. Herein, the assembly of drug-loaded polypeptide nanoparticles (NPs) with pH-sheddable modification of poly(ethylene glycol) (PEG) is prepared to enhance therapeutic efficiency. Poly(l-lysine) and poly(l-glutamic acid) were self-assembled to fabricate polypeptide NPs by electrostatic interactions, followed by PEGylation based on amidation reaction. The NP sizes can be controlled by tuning the molecular weight or the ratio of polypeptides. The PEG coating is cleavable at the tumor acid microenvironment to reverse the surface charge and reduce the NP size, which effectively enhances cell uptake. In addition, the presence of reducing reagent (e.g., glutathione) in cancer cells induces the drug (i.e., cisplatin) release from the polypeptide NPs and subsequently results in the cell toxicity. This reported method highlights the engineering of transformable polypeptide drug carriers, which provides a promising way for enhanced drug delivery efficacy.
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http://dx.doi.org/10.1021/acs.langmuir.0c02532DOI Listing
November 2020

Upper Respiratory Tract Viral Ribonucleic Acid Load at Hospital Admission Is Associated With Coronavirus Disease 2019 Disease Severity.

Open Forum Infect Dis 2020 Jul 5;7(7):ofaa282. Epub 2020 Jul 5.

Guangzhou Eighth People's Hospital, Guangzhou, China.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has aroused global public health concerns. Multiple clinical features relating to host profile but not for virus have been identified as the risk factors for illness severity and/or the outcomes in COVID-19.

Methods: The clinical features obtained from a cohort of 195 laboratory-confirmed, nasopharynx-sampled patients with COVID-19 in Guangdong, China from January 13 to February 29, 2020 were enrolled to this study. The differences in clinical features among 4 groups (mild, moderate, severe, and critical) and between 2 groups (severe vs nonsevere) were compared using one-way analysis of variance and Student's test, respectively. Principal component analysis and correlation analysis were performed to identify the major factors that account for illness severity.

Results: In addition to the previously described clinical illness severity-related factors, including older age, underlying diseases, higher level of C-reactive protein, D-dimer and aspartate aminotransferase, longer fever days and higher maximum body temperature, larger number of white blood cells and neutrophils but relative less lymphocytes, and higher ratio of neutrophil to lymphocytes, we found that the initial viral load is an independent factor that accounts for illness severity in COVID-19 patients.

Conclusions: The initial viral load of severe acute respiratory syndrome coronavirus 2 is a novel virological predictor for illness severity of COVID-19.
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http://dx.doi.org/10.1093/ofid/ofaa282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454839PMC
July 2020

Coblopasvir and sofosbuvir for treatment of chronic hepatitis C virus infection in China: A single-arm, open-label, phase 3 trial.

Liver Int 2020 11 13;40(11):2685-2693. Epub 2020 Oct 13.

Department of Hepatology, the First Hospital of Jilin University, Changchun, China.

Background & Aim: An affordable, pangenotypic regimen remains as an unmet medical need for chronic hepatitis C patients in China. This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of coblopasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic hepatitis C virus (HCV) infection.

Methods: Treatment-naïve and interferon-experienced adult patients, including those with advanced fibrosis (F3) or compensated cirrhosis (F4), were treated with a universal, combinational regimen of coblopasvir 60 mg and sofosbuvir 400 mg, once daily, for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12).

Results: Overall, 371 patients (men, 51%; age, 47 ± 11 years; genotype 1a < 1%, 1b 48%, 2a 26%, 3a 6%, 3b 7% and 6 12%) were enrolled from 19 sites. Fifty-one patients (14%) had F3, 39 patients (11%) had F4 and 39 patients (11%) were interferon experienced. The overall SVR12 was 97% (95% CI, [94%, 98%]) for the full analysis set and was equal to or above 90% for all predefined subsets. Ten patients (3%) experienced virological relapse and two patients did not complete follow-up. No adverse events (AEs) occurred at a frequency ≥5%, and the most often reported AEs (≥1%) were neutropenia and fatigue. The majority of AEs were mild to moderate and transient without specific medical intervention.

Conclusions: The universal, pangenotypic combo of coblopasvir plus sofosbuvir is an efficacious and safe treatment for Chinese patients monoinfected with HCV of genotype 1, 2, 3 and 6, including those with compensated cirrhosis.

Lay Summary: The regimen of coblopasvir and sofosbuvir is a safe and effective treatment for Chinese patients with genotype 1, 2, 3 and 6 HCV infection, including those with compensated cirrhosis. Therefore, this regimen would be a novel choice of treatment for this patient population.
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http://dx.doi.org/10.1111/liv.14633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702130PMC
November 2020

Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output.

Cell 2020 10 14;183(1):76-93.e22. Epub 2020 Sep 14.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address:

Mitochondria, which play central roles in immunometabolic diseases, have their own genome. However, the functions of mitochondria-located noncoding RNAs are largely unknown due to the absence of a specific delivery system. By circular RNA (circRNA) expression profile analysis of liver fibroblasts from patients with nonalcoholic steatohepatitis (NASH), we observe that mitochondrial circRNAs account for a considerable fraction of downregulated circRNAs in NASH fibroblasts. By constructing mitochondria-targeting nanoparticles, we observe that Steatohepatitis-associated circRNA ATP5B Regulator (SCAR), which is located in mitochondria, inhibits mitochondrial ROS (mROS) output and fibroblast activation. circRNA SCAR, mediated by PGC-1α, binds to ATP5B and shuts down mPTP by blocking CypD-mPTP interaction. Lipid overload inhibits PGC-1α by endoplasmic reticulum (ER) stress-induced CHOP. In vivo, targeting circRNA SCAR alleviates high fat diet-induced cirrhosis and insulin resistance. Clinically, circRNA SCAR is associated with steatosis-to-NASH progression. Collectively, we identify a mitochondrial circRNA that drives metaflammation and serves as a therapeutic target for NASH.
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http://dx.doi.org/10.1016/j.cell.2020.08.009DOI Listing
October 2020

Reappraisal of the diagnostic value of alpha-fetoprotein for surveillance of HBV-related hepatocellular carcinoma in the era of antiviral therapy.

J Viral Hepat 2021 01 22;28(1):20-29. Epub 2020 Sep 22.

Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

This study was designed to explore if antiviral treatment influences the performance of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) among the high-risk chronic HBV-infected patients. A total of 5936 patients who had evidence of chronic HBV infection were enrolled from four independent centres in this retrospective study, including 1721 chronic hepatitis B (CHB), 2286 liver cirrhosis (LC), 798 HCC within Milan criteria and 1131 HCC beyond Milan criteria patients. Stratified by whether they received treatment or not, the patients were further divided into antiviral and non-antiviral groups. Then, the performance of AFP for discriminating HCC was evaluated. Patients receiving antivirals had significantly lower median levels of AFP compared with the non-antiviral patients (P < .001), and there were significantly less patients with abnormal AFP levels in antiviral groups (P < .001). Antiviral therapy improved the AUROCs of AFP for discriminating HCC within Milan criteria. When setting the cut-off values at 20 ng/mL and 100 ng/mL as surveillance and confirmatory tests respectively for HCC among patients receiving antiviral treatment, AFP exhibited a significantly higher sensitivity than those of 200 ng/mL and 400 ng/mL, which are currently recommended by some guidelines, without compromising specificity. Further analysis in antiviral patients revealed that serum AFP had better performance for discriminating HCC within Milan criteria in ALT ≤ 1ULN patients than that in ALT > 1ULN patients. In conclusion, in the era of antiviral therapy, serum AFP's surveillance performance was substantially improved for HCC within Milan criteria among the high-risk population of CHB and LC patients.
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http://dx.doi.org/10.1111/jvh.13388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756791PMC
January 2021

Poly(ethylene glycol)-mediated mineralization of metal-organic frameworks.

Chem Commun (Camb) 2020 Sep;56(75):11078-11081

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China. and State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China.

We report a one-pot approach for the scalable synthesis of zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) using poly(ethylene glycol) as the mineralizer, where drugs and proteins can be encapsulated in the ZIF-8 NPs for intracellular delivery. The ZIF-8 NPs exhibit high colloidal dispersity and stability (above two weeks) in cell medium.
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http://dx.doi.org/10.1039/d0cc03734fDOI Listing
September 2020

Increased Expression of Fibulin-1 Is Associated With Hepatocellular Carcinoma Progression by Regulating the Notch Signaling Pathway.

Front Cell Dev Biol 2020 16;8:478. Epub 2020 Jun 16.

Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Fibulin-1, a component of the extracellular matrix (ECM), its prognostic, pathophysiologic and diagnostic role in hepatocellular carcinoma (HCC) is still unexplored. We first found that either Fibulin-1 messenger RNA (mRNA) or protein level was highly elevated in HCC tissues compared with normal tissues. Fibulin-1 correlated with poor overall survival, and it was an independent prognostic predictor ( = 0.001). Furthermore, Overexpression or inhibition of Fibulin-1 reduced or sensitized HCC cells to apoptotic signals, and Fibulin-1 silencing suppressed the ability of HCC cells to form tumors . Moreover, Fibulin-1 inhibited apoptosis via the Notch pathway while Fibulin-1 silencing had no obvious effect on p-MAPK, p-c-jun and p-stat3 expression, and both Mcl-1 and Bcl-xL are targets of Fibulin-1. Furthermore, the stromal and immune score was elevated in high Fibulin-1 tissues, and FBLN1 expression was associated with increased infiltrating macrophages using xCell, TIMER and TISDIB tool based on TCGA HCC database. Importantly, the circulating cell-free RNA (cfRNA) level of Fibulin-1 in the serum were significantly increased in patients with HCC compared with those in healthy controls, individuals with chronic hepatitis B and patients with HBV-induced liver cirrhosis. The area under receiver operating characteristic curves (AUC) was 0.791 for Fibulin-1, 0.640 for α-fetoprotein and 0.868 for the combination of the two tumor markers. Our findings indicate that Fibulin-1 may be a potential prognostic indicator, a promising serum biomarker and a therapeutic target in patients with HCC.
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http://dx.doi.org/10.3389/fcell.2020.00478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308487PMC
June 2020

A Predictive Model Using N-Glycan Biosignatures for Clinical Diagnosis of Early Hepatocellular Carcinoma Related to Hepatitis B Virus.

OMICS 2020 07 9;24(7):415-423. Epub 2020 Jun 9.

Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

Early diagnosis of hepatic cancer is a major public health challenge. While changes in serum N-glycans have been observed as patients progress from liver fibrosis/cirrhosis to hepatocellular carcinoma (HCC), the predictive performance of N-glycans is yet to be determined for HCC early diagnosis as well as differential diagnosis from liver fibrosis/cirrhosis. In a total sample of 247 patients with hepatitis B virus-related liver disease, we characterized and compared the serum N-glycans in very early/early and intermediate/advanced stages of HCC and those with liver fibrosis/cirrhosis. Additionally, we performed a retrospective timeline analysis of the serum N-glycans 6 and 12 months before a diagnosis of the very early/early stage of HCC (EHCC). A predictive model was built, named hereafter as Glycomics-EHCC, incorporating the glycan peaks (GPs) 1, 2, and 4. The model showed a larger area under the receiver operating characteristic curve compared with a traditional model with the α-fetoprotein (0.936 vs. 0.731, respectively). The Glycomics-EHCC model had a sensitivity of 84.6% and specificity of 85.0% at a cutoff value of -0.39 to distinguish EHCC from liver fibrosis/cirrhosis. Moreover, the Glycomics-EHCC model was able to forecast a future EHCC diagnosis with a sensitivity and specificity over 90% and 85%, respectively, using the serum N-glycan biosignatures 6 or 12 months earlier when the patients were suffering from liver fibrosis/cirrhosis before being diagnosed with EHCC. This serum glycomic biosignature model warrants further clinical studies in independent population samples and offers promise to forecast EHCC and its differential diagnosis from liver fibrosis/cirrhosis.
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http://dx.doi.org/10.1089/omi.2020.0055DOI Listing
July 2020

Fabrication of Poly(ethylene glycol) Capsules via Emulsion Templating Method for Targeted Drug Delivery.

Polymers (Basel) 2020 May 14;12(5). Epub 2020 May 14.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China.

To reduce nonspecific interactions and circumvent biological barriers, low-fouling material of poly(ethylene glycol) (PEG) is most used for the modification of drug nanocarriers. Herein, we report the fabrication of PEG capsules via the free-radical polymerization of linear PEG or 8-arm-PEG using an emulsion templating method for targeted drug delivery. Doxorubicin (DOX) could be loaded in capsules via electrostatic interactions. The obtained capsules composed of 8-arm-PEG result in a lower cell association (2.2%) compared to those composed of linear PEG (7.3%) and, therefore, demonstrate the stealth property. The functionalization of cyclic peptides containing Arg-Gly-Asp (cRGD) on PEG capsules induce high cell targeting to U87 MG cells. A cell cytotoxicity assay demonstrates the biocompatibility of PEG capsules and high drug delivery efficacy of the targeted capsules. The reported capsules with the stealth and targeting property provide a potential platform for improved drug delivery.
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http://dx.doi.org/10.3390/polym12051124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285215PMC
May 2020

SARS-CoV-2 can be detected in urine, blood, anal swabs, and oropharyngeal swabs specimens.

J Med Virol 2020 09 30;92(9):1676-1680. Epub 2020 Apr 30.

Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Purpose: The purpose of this study was to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA) in urine and blood specimens, and anal and oropharyngeal swabs from patients with confirmed SARS-CoV-2 infection, and correlated positive results with clinical findings.

Methods: Patients with confirmed SARS-CoV-2 infections were included in this study. Patients' demographic and clinical data were recorded. Quantitative real-time polymerase chain reaction was used to detect SARS-CoV-2 RNA in urine and blood specimens, and anal and oropharyngeal swabs. The study is registered at ClinicalTrials.gov (No. NCT04279782, 19 February, 2020).

Results: SARS-CoV-2 RNA was present in all four specimen types, though not all specimen types were positive simultaneously. The presence of viral RNA was not necessarily predictive of clinical symptoms, for example, the presence of viral RNA in the urine did not necessarily predict urinary tract symptoms.

Conclusions: SARS-CoV-2 can infect multiple systems, including the urinary tract. Testing different specimen types may be useful for monitoring disease changes and progression, and for establishing a prognosis.
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http://dx.doi.org/10.1002/jmv.25936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264521PMC
September 2020

Transcriptome alterations in HepG2 cells induced by shRNA knockdown and overexpression of gene.

Biosci Biotechnol Biochem 2020 Aug 23;84(8):1576-1584. Epub 2020 Apr 23.

Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou, Guangdong Province, China.

Transmembrane 2 () gene inhibits chronic hepatitis-B virus (HBV) infection, while the underlying molecular mechanisms remain unknown. Transcriptome alterations in HepG2 cells following overexpression or silencing by shRNA were analyzed by next-generation sequencing. Both overexpression and knockdown of the gene caused wide-spread changes in gene expression in HepG2 cells. Differentially expressed genes caused by altered gene expression were associated with multiple biological processes linked with viral infection and various signaling pathways. KEGG analysis revealed that many of the differentially expressed genes were enriched in the PI3K/AKT signaling pathway. Moreover, we show that genes related to the PI3K/AKT signaling pathway, such as , and , are biological targets regulated by in HepG2 cells. This is the first transcriptome-wide study in which -regulated genes in HepG2 cells have been screened. Our findings elucidate the molecular events associated with -mediated hepatocyte pathogenesis in chronic HBV infection.
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http://dx.doi.org/10.1080/09168451.2020.1756733DOI Listing
August 2020

Polypeptide-Based Theranostics with Tumor-Microenvironment-Activatable Cascade Reaction for Chemo-ferroptosis Combination Therapy.

ACS Appl Mater Interfaces 2020 May 27;12(18):20271-20280. Epub 2020 Apr 27.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.

Nanoengineering of polymer-based therapeutic carriers is promising for precise cancer treatment. Herein, we report the fabrication of polypeptide vehicles encapsulated with anticancer drug of cisplatin (Pt drug) and FeO nanoparticles (denoted as [email protected]) as theranostics for -weighted magnetic resonance imaging (MRI)-guided chemo-ferroptosis combination therapy. The number of FeO nanoparticles per polypeptide vehicle is well controlled by adjusting the added amount of FeO nanoparticles. The tumor microenvironment can trigger the release of Pt drug and Fe, which could induce the intracellular cascade reaction to generate sufficient OH for ferroptosis therapy. Moreover, the released Pt drug can cause the apoptosis of tumor cells. Meanwhile, the encapsulated FeO nanoparticles can also be used for -weighted MRI of tumor. Both and results indicate that the reported [email protected] can efficiently inhibit cancer cell growth without causing significant systemic toxicity. Importantly, polypeptide vehicles could significantly reduce the side effect of free Pt drug and therefore improve the drug delivery efficacy. Our findings suggest that polypeptide-based theranostics with tumor-microenvironment-activatable cascade reaction have great potential in biomedical applications.
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http://dx.doi.org/10.1021/acsami.0c03748DOI Listing
May 2020

Association between effective hepatic blood flow and the severity and prognosis of hepatitis B virus-related acute on chronic liver failure.

Eur J Gastroenterol Hepatol 2021 02;32(2):246-254

Department of Infectious Diseases.

Background: Hepatic inflammation resulted in hepatocyte necrosis and microcirculatory dysfunction in acute on chronic liver failure (ACLF) with cirrhosis or not. The influence of effective hepatic blood flow (EHBF) on the severity of liver failure has not been fully elucidated.

Aim: The aim of this study was to assess the correlation between the EHBF and the severity and the prediction of 90-day mortality rate of hepatitis B virus-related ACLF (HBV-ACLF).

Methods: In this retrospective study, patients hospitalized for HBV-ACLF or decompensated cirrhosis and who underwent an indocyanine green (ICG) clearance test between June 2016 and July 2018 were enrolled. EHBF was measured by the ICG clearance test and patients were categorized into the ACLF without cirrhosis (HBV-ACLF-no-Cir), ACLF with cirrhosis (HBV-ACLF-Cir) and decompensated cirrhosis (HBV-De-Cir).

Results: A total of 522 patients (HBV-ACLF-no-Cir: 84, HBV-ACLF-Cir: 111 and HBV-De-Cir: 327) were enrolled. The mean EHBF in the HBV-De-Cir was significantly higher than that in the HBV-ACLF-no-Cir and HBV-ACLF-Cir (0.36 vs. 0.21 vs. 0.20 L/min, P < 0.001). EHBF was significantly correlated with the total bilirubin, prothrombin activity and model for end-stage liver disease (MELD) in the HBV-ACLF-no-Cir. The predicted 90-day mortality rate using the MELD, EHBF, ICG-retention rate at 15 min (R15%) and EHBF-R15% scores were similar. The sensitivity and specificity of the EHBF varied between 68.5-80.2% and 45.8-73.7%, respectively. The EHBF-MELD score had the highest specificity.

Conclusion: EHBF was significantly lower in the patients with ACLF compared to decompensated cirrhosis. The EHBF were closely related to the severity of HBV-ACLF and can be used for predicting the 90-day mortality rate of HBV-ACLF.
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http://dx.doi.org/10.1097/MEG.0000000000001721DOI Listing
February 2021

A cross-sectional comparison of epidemiological and clinical features of patients with coronavirus disease (COVID-19) in Wuhan and outside Wuhan, China.

Travel Med Infect Dis 2020 May - Jun;35:101664. Epub 2020 Apr 9.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; GuangDong Provincial Key Laboratory of Liver Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: Coronavirus disease 2019 (COVID-19) has spread outside the initial epicenter of Wuhan. We compared cases in Guangzhou and Wuhan to illustrate potential changes in pathogenicity and epidemiological characteristics as the epidemic has progressed.

Methods: We studied 20 patients admitted to the Third Affiliated Hospital of Sun Yat-Sen University in Guangzhou, China from January 22 to February 12, 2020. Data were extracted from medical records. These cases were compared with the 99 cases, previously published in Lancet, from Wuhan Jinyintan Hospital from January 1 to January 20, 2020.

Results: Guangzhou patients were younger and had better prognosis than Wuhan patients. The Wuhan patients were more likely to be admitted to the ICU (23% vs 5%) and had a higher mortality rate (11% vs 0%). Cases in Guangzhou tended to be more community clustered. Diarrhea and vomiting were more common among Guangzhou patients and SARS-CoV-2 RNA was found in feces. Fecal SARA-CoV-2 RNA remained positive when nasopharyngeal swabs turned negative in some patients.

Conclusions: This study indicates possible diminishing virulence of the virus in the process of transmission. Yet persistent positive RNA in feces after negative nasopharyngeal swabs suggests a possible prolonged transmission period that challenges current quarantine practices.
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http://dx.doi.org/10.1016/j.tmaid.2020.101664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194579PMC
July 2020

Self-assembly of paramagnetic amphiphilic copolymers for synergistic therapy.

J Mater Chem B 2020 08;8(31):6866-6876

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.

Engineering nanoparticles (NPs) with multifunctionality has become a promising strategy for cancer theranostics. Herein, theranostic polymer NPs are fabricated via the assembly of amphiphilic paramagnetic block copolymers (PCL-b-PIEtMn), in which IR-780 and doxorubicin (DOX) were co-encapsulated, for magnetic resonance (MR) and near infrared fluorescence (NIRF) imaging as well as for photo thermal therapy (PTT)-enhanced chemotherapy. The synthesized amphiphilic paramagnetic block copolymers demonstrated high relaxivity (r1 = 7.05 mM-1 s-1). The encapsulated DOX could be released with the trigger of near infrared (NIR) light. In vivo imaging confirmed that the paramagnetic NPs could be accumulated effectively at the tumor sites. Upon the NIR laser irradiation, tumor growth was inhibited by PTT-enhanced chemotherapy. The advantages of the reported system lie in the one-step convergence of multiple functions (i.e., imaging and therapy agents) into a one delivery vehicle and the dual mode imaging-guided synergistic PTT and chemotherapy. This study represents a new drug delivery vehicle of paramagnetic NPs for visualized theranostics.
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http://dx.doi.org/10.1039/d0tb00405gDOI Listing
August 2020

Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report.

Int J Infect Dis 2020 Apr 5;93:297-299. Epub 2020 Mar 5.

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong, China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong, China. Electronic address:

The ongoing outbreak of COVID-19 that began in Wuhan, China, has constituted a Public Health Emergency of International Concern, with cases confirmed in multiple countries. Currently, patients are the primary source of infection. We report a confirmed case of COVID-19 whose oropharyngeal swab test of SARS-CoV-2 RNA turned positive in convalescence. This case highlights the importance of active surveillance of SARS-CoV-2 RNA for infectivity assessment.
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http://dx.doi.org/10.1016/j.ijid.2020.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129213PMC
April 2020

Liver Stiffness Measurement Can Reflect the Active Liver Necroinflammation in Population with Chronic Liver Disease: A Real-world Evidence Study.

J Clin Transl Hepatol 2019 Dec 11;7(4):313-321. Epub 2019 Dec 11.

Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

Non-invasive evaluation of liver necroinflammation in patients with chronic liver disease is an unmet need in clinical practice. The diagnostic accuracy of transient elastography-based liver stiffness measurement (LSM) for liver fibrosis could be affected by liver necroinflammation, the latter of which could intensify stiffness of the liver. Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation. Three cross-sectional cohorts of liver biopsy-proven chronic liver disease patients were enrolled, including 1417 chronic hepatitis B (CHB) patients from 10 different medical centers, 106 non-alcoholic steatohepatitis patients, and 143 patients with autoimmune-related liver diseases. Another longitudinal cohort of 14 entecavir treatment patients was also included. The receiver operating characteristic (ROC) curve was employed to explore the diagnostic value of LSM. In CHB patients, LSM value ascended with the increased severity of liver necroinflammation in patients with the same fibrosis stage. Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoimmune-related liver diseases populations. Furthermore, the ROC curve exhibited that LSM could identify moderate and severe inflammation in CHB patients (area under the ROC curve as 0.779 and 0.838) and in non-alcoholic steatohepatitis patients (area under the ROC curve as 0.826 and 0.871), respectively. Such moderate diagnostic value was also found in autoimmune-related liver diseases patients. In addition, in the longitudinal entecavir treated CHB cohort, a decline of LSM values was observed in parallel with the control of inflammatory activity in liver. Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.
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http://dx.doi.org/10.14218/JCTH.2019.00040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943212PMC
December 2019

Antifouling and pH-Responsive Poly(Carboxybetaine)-Based Nanoparticles for Tumor Cell Targeting.

Front Chem 2019 22;7:770. Epub 2019 Nov 22.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, China.

Nanocarriers with responsibility and surface functionality of targeting molecules have been widely used to improve therapeutic efficiency. Hence, we report the assembly of pH-responsive and targeted polymer nanoparticles (NPs) composed of poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) as the core and poly(carboxybetaine methacrylate) (PCBMA) as the shell, functionalized with cyclic peptides containing Arginine-Glycine-Aspartic acid--Phenylalanine-Lysine (RGD). The resulting polymer NPs ([email protected] NPs) can maintain the pH-responsivity of PDPA (pKa ~6.5) and low-fouling property of PCBMA that significantly resist non-specific interactions with RAW 264.7 and HeLa cells. Meanwhile, [email protected] NPs could specifically target αβ integrin-expressed human glioblastoma (U87) cells. The pH-responsiveness and low-fouling properties of [email protected] NPs are comparable to [email protected](ethylene glycol) ([email protected]) NPs, which indicates that PCBMA is an alternative to PEG for low-fouling coatings. The advantage of [email protected] NPs lies in the presence of carboxyl groups on their surfaces for further modification (e.g., RGD functionalization for cell targeting). The reported polymer NPs represent a new carrier that have the potential for targeted therapeutic delivery.
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http://dx.doi.org/10.3389/fchem.2019.00770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883901PMC
November 2019

Dual pH-Responsive Polymer Nanogels with a Core-Shell Structure for Improved Cell Association.

Langmuir 2019 12 9;35(51):16869-16875. Epub 2019 Dec 9.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering , Shandong University , Jinan , Shandong 250100 , China.

We report the fabrication of polymer nanogels with a pH-responsive core and a pH-sheddable shell and investigate the pH-dependent cell association of the pH-responsive polymer nanogels. The pH-responsive core composed of poly(2-diisopropylaminoethyl methacrylate) (PDPA) with a p ≈ 6.2 was synthesized by using polymerization in emulsion droplets. The pH-sheddable poly(ethylene glycol) (PEG) shell was coated on the amine-modified PDPA nanogels by an acid-degradable amide bond. The PEG shell is cleavable in response to the acidic tumor microenvironment, and subsequently, the surface charge of the nanogels can be reversed, which effectively enhances cellular association of these nanogels. The reported pH-responsive polymer nanogels provide a promising way for the better understanding of bio-nano interactions and potentially enrich the application of therapeutic delivery for cancer therapy.
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http://dx.doi.org/10.1021/acs.langmuir.9b03107DOI Listing
December 2019

Forkhead box (FOX) G1 promotes hepatocellular carcinoma epithelial-Mesenchymal transition by activating Wnt signal through forming T-cell factor-4/Beta-catenin/FOXG1 complex.

J Exp Clin Cancer Res 2019 Nov 27;38(1):475. Epub 2019 Nov 27.

Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, Guangzhou, 510630, Guangdong Province, China.

Background: Forkhead box G1 (FOXG1) is a member of the Fox transcription factor family involved in regulation of many cancers. However, the role of FOXG1 in hepatocellular carcinogenesisis largely unclear. The present study aimed at examining the biological function and underlying mechanism of FOXG1 on hepatocellular carcinoma (HCC) tumor metastasis as well as its clinical significance.

Methods: Levels of FOXG1 were determined by immunohistochemical and real-time PCR analysis in HCC cell lines and human HCC samples. The effect of FOXG1 on cancer cell invasion and metastasis was investigated in vitro and in vivo in either FOXG1-silenced or overexpressing human HCC cell lines. Immunoprecipitation and chromatin immunoprecipitation assays were performed to investigate the interaction of FOXG1, β-catenin, TCF4 and the effect on Wnt target-gene promoters.

Results: In human HCC, the level of FOXG1 progressively increased from surrounding non tumorous livers to HCC, reaching the highest levels in metastatic HCC. Furthermore, expression levels of FOXG1 directly correlated with cancer cell epithelial-mesenchymal transition (EMT) phenotype. In FOXG1-overexpressing cells, FOXG1 promotes the stabilization and nuclear accumulation of β-catenin by directly binding to β-catenin and it associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs) on Wnt responsive enhancers (WREs) in chromatin.

Conclusions: The results show that FOXG1 plays a key role in mediating cancer cell metastasis through the Wnt/β-catenin pathway in HCC cells and predicts HCC prognosis after surgery. Targeting FOXG1 may provide a new approach for therapeutic treatment in the future.
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http://dx.doi.org/10.1186/s13046-019-1433-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880489PMC
November 2019

A Potential Functional Cure in Chinese HBeAg-negative Chronic Hepatitis B Patients Treated with Peg-interferon Alpha-2a.

J Clin Transl Hepatol 2019 Sep 20;7(3):249-257. Epub 2019 Aug 20.

Department of Liver Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Data are limited on the use of pegylated-interferon alpha-2a (peg-IFNα) in Chinese patients with chronic hepatitis B virus (HBV) infection (CHB). We evaluated the effectiveness and safety of peg-IFNα in Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice. In this prospective, multicenter, observational, non-interventional cohort study, patients were assessed for up to 1 year after peg-IFNα treatment cessation. Treating physicians established the dosing and treatment duration according to Chinese clinical practice. Effectiveness of peg-IFNα treatment was measured by the percentage of: patients with HBV DNA <2000 IU/mL and loss of hepatitis B surface antigen (commonly known as HBsAg); HBV DNA level at end of treatment (EOT), and 6 months and 1 year posttreatment; and time course change in quantitative HBV DNA and HBsAg. At EOT, 6 months posttreatment, and 1 year posttreatment, the percentage of patients with HBV DNA <2000 IU/mL was 90.0%, 81.8%, and 82.2%, and that of patients with HBsAg loss was 6.5%, 9.4%, and 9.5%, respectively. The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment. The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment. The incidence of adverse events was 52.0%. Peg-IFNα has the potential to provide functional cure (HBsAg loss) for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China. ClinicalTrials.gov (NCT01730508).
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http://dx.doi.org/10.14218/JCTH.2019.00016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783682PMC
September 2019
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