Publications by authors named "Fengmei Wang"

108 Publications

Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer.

Front Oncol 2021 22;11:650453. Epub 2021 Apr 22.

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Increasing evidence shows that the extracellular matrix (ECM) is an important regulator of breast cancer (BC). The ECM comprises of highly variable and dynamic components. Compared with normal breast tissue under homeostasis, the ECM undergoes many changes in composition and organization during BC progression. Induced ECM proteins, including fibrinogen, fibronectin, hyaluronic acid, and matricellular proteins, have been identified as important components of BC metastatic cells in recent years. These proteins play major roles in BC progression, invasion, and metastasis. Importantly, several specific ECM molecules, receptors, and remodeling enzymes are involved in promoting resistance to therapeutic intervention. Additional analysis of these ECM proteins and their downstream signaling pathways may reveal promising therapeutic targets against BC. These potential drug targets may be combined with new nanoparticle technologies. This review summarizes recent advances in functional nanoparticles that target the ECM to treat BC. Accurate nanomaterials may offer a new approach to BC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.650453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100244PMC
April 2021

Controlled synthesis and Raman study of a 2D antiferromagnetic P-type semiconductor: α-MnSe.

Nanoscale 2021 Apr 7;13(14):6953-6964. Epub 2021 Apr 7.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.

Two-dimensional (2D) non-van der Waals magnetic materials have attracted considerable attention due to their high-temperature ferromagnetism, active surface/interface properties originating from dangling bonds, and good stability under ambient conditions. Here, we demonstrate the controlled synthesis and systematic Raman investigation of ultrathin non-van der Waals antiferromagnetic α-MnSe single crystals. Square and triangular nanosheets with different growth orientations can be achieved by introducing different precursors via the atmospheric chemical vapor deposition (APCVD) method. The temperature-dependent resonant enhancement in the Raman intensity of two peaks at 233.8 cm and 459.9 cm gives obvious evidence that the antiferromagnetic spin-ordering is below T∼ 160 K. Besides, a new peak located at 254.2 cm, gradually appearing as the temperature decreased from 180 K to 100 K, may also be a signature of phase transition from paramagnetic to antiferromagnetic. The phonon dispersion spectra of α-MnSe simulated by density functional perturbation theory (DFPT) match well with the observed Raman signals. Moreover, a fabricated α-MnSe phototransistor exhibits p-type conducting behavior and high photodetection performance. We believe that these findings will be beneficial for the applications of 2D α-MnSe in magnetic and semiconducting fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1nr00822fDOI Listing
April 2021

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases.

Front Immunol 2021 31;12:664871. Epub 2021 Mar 31.

Department of Pharmacy, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China.

Osteoimmunity is involved in regulating the balance of bone remodeling and resorption, and is essential for maintaining normal bone morphology. The interaction between immune cells and osteoclasts in the bone marrow or joint cavity is the basis of osteoimmunity, in which the macrophage-osteoclast axis plays a vital role. Monocytes or tissue-specific macrophages (macrophages resident in tissues) are an important origin of osteoclasts in inflammatory and immune environment. Although there are many reports on macrophages and osteoclasts, there is still a lack of systematic reviews on the macrophage-osteoclast axis in osteoimmunity. Elucidating the role of the macrophage-osteoclast axis in osteoimmunity is of great significance for the research or treatment of bone damage caused by inflammation and immune diseases. In this article, we introduced in detail the concept of osteoimmunity and the mechanism and regulators of the differentiation of macrophages into osteoclasts. Furthermore, we described the role of the macrophage-osteoclast axis in typical bone damage caused by inflammation and immune diseases. These provide a clear knowledge framework for studying macrophages and osteoclasts in inflammatory and immune environments. And targeting the macrophage-osteoclast axis may be an effective strategy to treat bone damage caused by inflammation and immune diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.664871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044404PMC
March 2021

Nonlayered Tin Thiohypodiphosphate Nanosheets: Controllable Growth and Solar-Light-Driven Water Splitting.

ACS Appl Mater Interfaces 2021 Mar 15;13(11):13392-13399. Epub 2021 Mar 15.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.

As a promising candidate in various fields, including energy conversion and electronics, layered van der Waals metal phosphorus trichalcogenides (MPX) have been widely explored. In addition to the layered structures, MPX comprising post-transition metals (i.e., Sn and Pb) are known to form a unique 3D framework with nonlayered structure. However, the nonlayered two-dimensional (2D) crystals of this family have remained unexplored until now. Herein, we successfully synthesized 2D nonlayered tin thiohypodiphosphate (SnPS) nanosheets, having an indirect bandgap of 2.25 eV and a thickness down to ∼10 nm. The as-obtained nanosheets demonstrate promising photocatalytic water splitting activity to generate H in pure water under simulated solar light (AM 1.5G). Moreover, the ultrathin SnPS catalyst shows auspicious performance and stability with a continuous operation of 40 h. This work is not only an expansion of the MPX family, but it is also a major milestone in the search for new materials for future energy conversion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c00038DOI Listing
March 2021

A thermochromic tissue-mimicking phantom model for verification of ablation plans in thermal ablation.

Ann Transl Med 2021 Feb;9(4):354

Department of Ultrasound, Tianjin Third Central Hospital, Tianjin, China.

Background: Our study aims to develop a novel tissue-mimicking thermochromic with tumor model for visualization of thermal ablation and verification of ablation plans.

Methods: Polyacrylamide gel was mixed with thermochromic ink to produce a phantom model. A phantom model embedded in a tumor model was constructed and used to evaluate the ablation procedure. The phantom models were randomly divided into complete ablation group and incomplete ablation group. The ablation planning of the tumor was on the 3D US and performed on a phantom model. We guide the ablation procedures according to the ablation planning. The results measured in a gross specimen of the phantom model were compared with the expected results in ablation planning.

Results: The color of the model changes from cream white to magenta after heating. The mono-site ablation area is a spheroid after thermal ablation with a size of 3.0×1.8 cm at 60 W, 5 minutes, 3.5×2.5 cm at 60 W, 10 minutes, and 4.0×3.5 cm at 60 W, 15 minutes, respectively. According to the ablation planning, a total of 4 ablation points were needed to retrieve the complete ablation of a 3.0 cm tumor. The complete ablation and incomplete ablation were proved by a gross specimen of the phantom model as we expected.

Conclusions: A novel thermochromic tissue-mimicking phantom model with a spherical tumor model has been designed and developed. The ablation area can be visualized on this phantom model by the permanent color change. This phantom model can assess the ablation planning system's accuracy and train operators for ultrasound-guided thermal ablation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-21-523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944255PMC
February 2021

Tacrolimus-induced epilepsy with primary membranous nephropathy: A case report.

Medicine (Baltimore) 2021 Mar;100(9):e24989

Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing.

Rationale: Tacrolimus-associated neurologic disorders can be found in some cases, mainly in organ transplantation patients. However, epilepsy induced by tacrolimus in primary membranous nephropathy (PMN) patient is scare.

Patient Concerns: A 63-year-old man experienced 1-year history of foamy urine, and edema of lower extremity.

Diagnosis: The patient had proteinuria, hypoalbuminemia, which indicated nephrotic syndrome. Further, we performed renal biopsy for this patient. Combined with the renal biopsy result, the diagnosis of primary membranous nephropathy was established.

Intervention: At first, irbesartan was administrated for 6 months. However, the proteinuria had no obvious improvement. Tacrolimus was administrated afterwards.

Outcomes: Twenty-two days after tacrolimus treatment, epilepsy occurred. Sodium valproate and carbamazepine were successively given to control epilepsy. However, the epileptic symptoms were not effectively controlled. During the treatment, the concentration of tacrolimus fluctuated greatly. At last, levetiracetam was given to maintain the curative effect. Fortunately, the patient did not suffer from epilepsy again. The concentration of temporary tacrolimus was stable, whereas proteinuria gradually decreased.

Lessons: Tacrolimus-induced epilepsy should be considered in patients exhibiting acute neurological symptoms. Early diagnosis and effective treatment play a vital role for favorable prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939194PMC
March 2021

The Ubiquitin E3 Ligase TRIM21 Promotes Hepatocarcinogenesis by Suppressing the p62-Keap1-Nrf2 Antioxidant Pathway.

Cell Mol Gastroenterol Hepatol 2021 19;11(5):1369-1385. Epub 2021 Jan 19.

Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey; Cancer Metabolism and Growth Program, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. Electronic address:

Background And Aims: TRIM21 is a ubiquitin E3 ligase that is implicated in numerous biological processes including immune response, cell metabolism, redox homeostasis, and cancer development. We recently reported that TRIM21 can negatively regulate the p62-Keap1-Nrf2 antioxidant pathway by ubiquitylating p62 and prevents its oligomerization and protein sequestration function. As redox homeostasis plays a pivotal role in many cancers including liver cancer, we sought to determine the role of TRIM21 in hepatocarcinogenesis.

Methods: We examined the correlation between TRIM21 expression and the disease using publicly available data sets and 49 cases of HCC clinical samples. We used TRIM21 genetic knockout mice to determine how TRIM21 ablation impact HCC induced by the carcinogen DEN plus phenobarbital (PB). We explored the mechanism that loss of TRIM21 protects cells from DEN-induced oxidative damage and cell death.

Results: There is a positive correlation between TRIM21 expression and HCC. Consistently, TRIM21-knockout mice are resistant to DEN-induced hepatocarcinogenesis. This is accompanied by decreased cell death and tissue damage upon DEN treatment, hence reduced hepatic tissue repair response and compensatory proliferation. Cells deficient in TRIM21 display enhanced p62 sequestration of Keap1 and are protected from DEN-induced ROS induction and cell death. Reconstitution of wild-type but not the E3 ligase-dead and the p62 binding-deficient mutant TRIM21 impedes the protection from DEN-induced oxidative damage and cell death in TRIM21-deficient cells.

Conclusions: Increased TRIM21 expression is associated with human HCC. Genetic ablation of TRIM21 leads to protection against oxidative hepatic damage and decreased hepatocarcinogenesis, suggesting TRIM21 as a preventive and therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmgh.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024979PMC
January 2021

Regulating Gut Microbiome: Therapeutic Strategy for Rheumatoid Arthritis During Pregnancy and Lactation.

Front Pharmacol 2020 11;11:594042. Epub 2020 Nov 11.

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and bone destruction. Microbial infection is considered to be the most important inducement of RA. The pregnancy planning of women in childbearing age is seriously affected by the disease activity of RA. Gut microbiome, related to immunity and inflammatory response of the host. At present, emerging evidence suggested there are significant differences in the diversity and abundance of gut microbiome during pregnancy and lactation, which may be associated with the fluctuation of RA disease activity. Based on these research foundations, we pioneer the idea of regulating gut microbiome for the treatment of RA during pregnancy and lactation. In this review, we mainly introduce the potential treatment strategies for controlling the disease activity of RA based on gut microbiome during pregnancy and lactation. Besides, we also briefly generalize the effects of conventional anti-rheumatic drugs on gut microbiome, the effects of metabolic changes during pregnancy on gut microbiome, alteration of gut microbiome during pregnancy and lactation, and the effects of anti-rheumatic drugs commonly used during pregnancy and lactation on gut microbiome. These will provide a clear knowledge framework for researchers in immune-related diseases during pregnancy. Regulating gut microbiome may be a potential and effective treatment to control the disease activity of RA during pregnancy and lactation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.594042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748111PMC
November 2020

Predicting the survival rate of patients with hepatocellular carcinoma after thermal ablation by nomograms.

Ann Transl Med 2020 Sep;8(18):1159

Department of Ultrasound, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin, China.

Background: To accurately predict the survival rate of patients with hepatocellular carcinoma (HCC) undergoing thermal ablation using nomograms taking early recurrence into account as a risk factor.

Methods: A total of 591 patients receiving percutaneous thermal ablation were included in this study. The overall survival (OS) and recurrence-free survival (RFS) rate was analyzed. Two prognostic nomograms with or without taking early recurrence into account as a risk factor were constructed using the independent predictors assessed by the multivariate Cox proportional hazard model. The performance of the nomograms, in terms of discrimination and calibration, was evaluated.

Results: The cumulative RFS and OS rates at 1-, 3- and 5-year are 82.2%, 52.5%and 38.4%, 96.6%, 83.6% and 65.5%, respectively. Multivariate analysis without considering the early recurrence shows that tumor number, α-fetoprotein (AFP) level, liver function, and GGT level are associated with OS. The early recurrence, tumor number, AFP level, and liver function are considered associated with the OS when considering early recurrence. Two different nomograms were developed from the above two results. Internal validation with 1,000 bootstrapped sample sets of the two nomograms shows the concordance indexes of 0.69 (95% CI: 0.624-0.748) for the baseline nomogram and 0.81 (95% CI: 0.754-0.857) for the early recurrence-based nomogram, with the latter significantly better in discriminating performance (Z statistics =92.19, P<0.0001).

Conclusions: The survival rate of patients with HCC undergoing radical thermal ablation can be reliably predicted by the nomogram presented in this study, which was developed by taking early recurrence into account.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-6116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576088PMC
September 2020

Speeding protons with metal vacancies.

Authors:
Fengmei Wang Jun He

Science 2020 10;370(6516):525-526

Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abe6166DOI Listing
October 2020

[Dynamic measurement of volume of atelectasis area in the evaluation of the prognosis of patients with moderate-to-severe acute respiratory distress syndrome].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Sep;32(9):1056-1060

Department of Critical Care Medicine, Tianjin Third Central Hospital, Tianjin 300170, China.

Objective: To assess the impact of not inflated lung tissue (NILT) volume on the prognosis of patients with moderate-to-severe acute respiratory distress syndrome (ARDS).

Methods: The clinical data of 131 patients with moderate-to-severe ARDS admitted to the intensive care unit (ICU) of Tianjin Third Central Hospital from March 2016 to June 2019 were collected. The basic data of patients, including gender, age, body mass index (BMI), causes of ARDS, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score and oxygenation index (PaO/FiO), were collected. The CT imaging data of patients on the 1st and 7th day in the ICU were collected. According to the CT value, they were divided into hyperventilated areas (-1 000 to -900 HU), normal ventilation areas (-899 to -500 HU), poorly ventilated areas (-499 to -100 HU), and atelectasis area (-99 to 100 HU). The total lung volume and the percentage of NILT to the total lung volume (NILT%) were calculate. At the same time, duration of mechanical ventilation, length of ICU stay, total length of hospital stay were collected. According to the 28-day follow-up, they were divided into survival group and death group. Multivariate Logistic regression analysis was used to determine the risk factors for 28-day death in ARDS patients. The receiver operating characteristic (ROC) curve was drawn, the area under ROC curve (AUC) and 95% confidence interval (95%CI) were calculated to determine the accuracy of NILT% in predicting the 28-day prognosis of ARDS patients, and the NILT% threshold was used for subgroup analysis of patients.

Results: Among the 131 patients with moderate-to-severe ARDS, patients were excluded for more than 48 hours after ARDS diagnosis, repeated admission to ICU due to ARDS, the ICU duration less than 7 days, death within 72 hours of admission, chronic interstitial lung disease or congestive heart failure, no chest CT examination within 7 days of admission to ICU, and no specimen collection within 2 hours of admission to ICU. Finally, a total of 53 patients were enrolled in the analysis. Of the 53 patients, 31 patients survived and 22 patients died. The 28-day mortality was 41.5%. Compared with the survival group, patients in the death group were older (years old: 65.32±11.29 vs. 55.77±14.23), and had a higher SOFA score (11.68±3.82 vs. 8.39±2.23) with significant differences (both P < 0.05), while there were no significant differences in gender, BMI, ARDS cause, APACHE II score and PaO/FiO between the two groups. There was no significant difference in CT value, total lung volume and NILT% between the two groups at 1st day after admission to ICU; NILT% on day 7 after admission to ICU in the death group was significantly higher than that in the survival group [(28.95±8.40)% vs. (20.35±5.91)%, P < 0.01], but there was no significant difference in CT value and total lung volume between the two groups. Multivariate Logistic regression analysis showed that the 28-day prognosis of ARDS was related to age, SOFA score and NILT% independently [age: odds ratio (OR) = 0.892, 95%CI was 0.808-0.984, P = 0.023; SOFA score: OR = 0.574, 95%CI was 0.387-0.852, P = 0.006; NILT%: OR = 0.841, 95%CI was 0.730-0.968, P = 0.016]. ROC curve analysis showed that 7-day NILT% could predict the 28-day prognosis of patients with moderate-to-severe ARDS, and AUC was 0.810 (95%CI was 0.678-0.952, P < 0.01). The NILT% threshold was 15.50%, sensitivity was 95.5%, specificity was 80.6%, positive predictive value was 85.7%, and negative predictive value was 74.6%. According to the 7-day NILT% threshold, a subgroup analysis of patients was performed, and 7-day NILT% > 15.50% was defined as a high-risk clinical prognosis, and ≤ 15.50% was a low-risk. Compared with low-risk patients (n = 7), the duration of mechanical ventilation, the length of ICU stay and total length of hospital stay in high-risk patients (n = 46) were significantly prolonged [duration of mechanical ventilation (days): 9.37±6.14 vs. 4.43±1.72, length of ICU stay (days): 12.11±5.85 vs. 7.57±1.13, total length of hospital stay (days): 18.39±5.87 vs. 11.29±2.22, all P < 0.05].

Conclusions: The 7-day NILT% > 15.50% of patients with moderate-to-severe ARDS after ICU admission is related to poor prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.cn121430-20191219-00056DOI Listing
September 2020

Validation of Baveno VI and expanded Baveno VI criteria to identify high-risk varices in patients with MAFLD-related compensated cirrhosis.

J Hepatol 2020 12 21;73(6):1571-1573. Epub 2020 Sep 21.

CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2020.06.042DOI Listing
December 2020

Additional Diagnostic Value of Fusion Imaging of CEUS and First CEUS of Invisible Hepatic Lesions ≤2 cm.

J Ultrasound Med 2021 Jun 17;40(6):1173-1181. Epub 2020 Sep 17.

Department of Ultrasound, Tianjin Third Central Hospital, Tianjin, 300170, China.

Objective: To explore the clinical value of image fusion of contrast-enhanced ultrasonography (CEUS) and contrast-enhanced computed tomography (CECT) in the diagnosis of invisible lesions with a size ≤2 cm on conventional ultrasound imaging, and compare it with the clinical value of "first CEUS" .

Methods: A total of 132 patients with 147 lesions with abnormal blood supply with a size ≤2 cm on CECT were included in this study. "first CEUS" was performed for these lesions. Then "fusion CEUS," that is, CEUS administered after fusion of US and CECT images, was carried out. The detection rates of the "first CEUS" and "fusion CEUS" were compared. How "fusion CEUS" corrects the misdiagnosis of liver lesions on CECT was analyzed.

Results: One hundred nine lesions considered as HCC and 38 lesions considered as benign lesions on CECT were included. The detection rates for the lesions of "first CEUS" and "fusion CEUS" were 71.4% and 96.6%, respectively (P < 0.001). Among the 147 lesions, 68 were with a diameter ≤ 1 cm. The detection rate of "first CEUS" and "fusion CEUS" were 55.9% and 95.6%, respectively (P < 0.001) for the lesions with a size ≤1 cm. "Fusion CEUS" and "first CEUS" corrected the misdiagnosis in 2 lesions on CECT.

Conclusion: The "first CEUS" and "fusion CEUS" can improve the lesion conspicuity. Compared with "first CEUS," "fusion CEUS" has a higher diagnostic ability and hence can detect most of the invisible lesions on the former.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jum.15498DOI Listing
June 2021

High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b.

J Gastroenterol Hepatol 2021 Mar 5;36(3):767-774. Epub 2020 Aug 5.

Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.

Background And Aim: Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3.

Methods: The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index).

Results: We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg . The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin).

Conclusions: In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.15192DOI Listing
March 2021

Contrast-enhanced ultrasound LI-RADS 2017: comparison with CT/MRI LI-RADS.

Eur Radiol 2021 Feb 15;31(2):847-854. Epub 2020 Aug 15.

Department of Gastroenterology and Hepatology, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin Third Central Hospital, Tianjin, 300170, China.

Objective: To compare the classification based on contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) with that of contrast-enhanced CT and MRI (CECT/MRI) LI-RADS for liver nodules in patients at high risk of hepatocellular carcinoma.

Methods: Two hundred thirty-nine patients with 273 nodules were enrolled in this retrospective study. Each nodule was categorized according to the CEUS LI-RADS version 2017 and CECT/MRI LI-RADS version 2017. The diagnostic performance of CEUS and CECT/MRI was compared. The reference standard was histopathology diagnosis. Inter-modality agreement was assessed with Cohen's kappa.

Results: The inter-modality agreement for CEUS LI-RADS and CECT/MRI LI-RADS was fair with a kappa value of 0.319 (p < 0.001). The positive predictive values (PPVs) of hepatocellular carcinoma (HCC) in LR-5, LR-4, and LR-3 were 98.3%, 60.0%, and 25.0% in CEUS, and 95.9%, 65.7%, and 48.1% in CECT/MRI, respectively. The sensitivities and specificities of LR-5 for diagnosing HCC were 75.6% and 93.8% in CEUS, and 83.6% and 83.3% in CECT/MRI, respectively. The positive predictive values of non-HCC malignancy in CEUS LR-M and CECT/MRI LR-M were 33.9% and 93.3%, respectively. The sensitivity, specificity, and accuracy for diagnosing non-HCC malignancy were 90.9%, 84.5%, and 85.0% in CEUS LR-M and 63.6%, 99.6%, and 96.7% in CECT/MRI LR-M, respectively.

Conclusions: The inter-modality agreement of the LI-RADS category between CEUS and CECT/MRI is fair. The positive predictive values of HCCs in LR-5 of the CEUS and CECT/MRI LI-RADS are comparable. CECT/MRI LR-M has better diagnostic performance for non-HCC malignancy than CEUS LR-M.

Key Points: • The inter-modality agreement for the final LI-RADS category between CEUS and CECT/MRI is fair. • The LR-5 of CEUS and CECT/MRI LI-RADS corresponds to comparable positive predictive values (PPVs) of HCC. For LR-3 and LR-4 nodules categorized by CECT/MRI, CEUS examination should be performed, at least if they can be detected on plain ultrasound. • CECT/MRI LR-M has better diagnostic performance for non-HCC malignancy than CEUS LR-M. For LR-M nodules categorized by CEUS, re-evaluation by CECT/MRI is necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-07159-zDOI Listing
February 2021

Evaluation of HBV serological markers in treatment-naïve HBV mono-infected patients and HBV-HIV co-infected patients.

Virus Res 2020 12 13;290:198117. Epub 2020 Aug 13.

Tianjin Second People's Hospital, Tianjin, 300192, PR China; Tianjin Institute of Hepatology, Tianjin, 300192, PR China. Electronic address:

Objectives: Many studies have investigated the utility of hepatitis B virus (HBV) serological markers in HBV-infected patients. However, only a few studies have examined HBV serological markers in HBV-human immunodeficiency virus (HIV) co-infected patients. Here, we conducted a cross-sectional study to evaluate correlations of HBV serological markers in treatment-naïve HBV mono-infected patients and HBV-HIV co-infected patients.

Methods: HBsAg, HBV DNA, HBV RNA, and HBcrAg were quantified in 51 HBV mono-infected patients and 33 HBV-HIV co-infected patients recruited at Tianjin Second People's Hospital from 2016 to 2019.

Results: There was no significant difference in serum levels of HBV DNA (P = 0.056), HBV RNA (P = 0.387), HBcrAg (P = 0.714) and HBsAg (P = 0.165) between the patient groups. In HBV mono-infected patients, strong positive correlations were confirmed between HBV RNA and HBV DNA (r=0.620, P < 0.01), HBcrAg and HBV DNA (r=0.802, P < 0.001), and HBcrAg and HBV RNA (r=0.727, P < 0.01). In HBV-HIV co-infected patients, serum HBsAg was very strongly correlated with HBcrAg (r=0.838, P < 0.001). In HBeAg-positive HBV mono-infected patients, all HBV serological markers correlated with each other, whereas only HBV RNA correlated with HBcrAg in HBeAg-negative HBV mono-infected patients (r=0.688, P = 0.007). In HBeAg-positive HBV-HIV co-infected patients, only HBsAg correlated with HBcrAg (r=0.725, P<0.001), whereas HBcrAg and HBV RNA correlated with each other in HBeAg-negative patients (r = 0.683, P=0.010). Moreover, CD4 T-cell counts were not significantly associated with HBsAg, HBV DNA, HBV RNA, and HBcrAg levels.

Conclusion: Compared with HBsAg and HBV DNA, which are widely used in clinical settings, our study confirmed that new HBV serological markers, such as HBV RNA and HBcrAg, have some utility in HBV mono-infected patients and HBV-HIV co-infected patients for monitoring the progression of liver disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virusres.2020.198117DOI Listing
December 2020

Sustained delivery of 17β-estradiol by human amniotic extracellular matrix (HAECM) scaffold integrated with PLGA microspheres for endometrium regeneration.

Drug Deliv 2020 Dec;27(1):1165-1175

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The endometrial injury usually results in intrauterine adhesions (IUAs). However, there is no effective treatment to promote the regeneration of the endometrium currently. The decellularized amnion membrane (AM) is a promising material in human tissue repair and regeneration due to its biocompatibility, biodegradability, as well as the preservation of abundant bioactive components. Here, an innovative drug-delivering system based on human amniotic extracellular matrix (HAECM) scaffolds were developed to facilitate endometrium regeneration. The 17β-estradiol (E) loaded PLGA microspheres (E-MS) were well dispersed in the scaffolds without altering their high porosity. E released from E-MS-HAECM scaffolds showed a decreased initial burst release followed with a sustained release for 21 days, which coincided with the female menstrual cycle. Results of cell proliferation suggested E-MS-HAECM scaffolds had good biocompatibility and provided more biologic guidance of endometrial cell proliferation except for mechanical supports. Additionally, the mRNA expression of growth factors in endometrial cells indicated that HAECM scaffolds could upregulate the expression of EGF and IGF-1 to achieve endometrium regeneration. Therefore, these advantages provide the drug-loaded bioactive scaffolds with new choices for the treatments of IUAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10717544.2020.1801891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470125PMC
December 2020

Clinical course of COVID-19 in patients with pre-existing decompensated cirrhosis: initial report from China.

Hepatol Int 2020 Jul 22;14(4):478-482. Epub 2020 May 22.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Background: The clinical characteristics and disease course in COVID-19 patients with pre-existing decompensated cirrhosis has not been described so far.

Methods: In this case series, we report three patients with confirmed COVID-19 and pre-existing decompensated cirrhosis from three hospitals in Hubei, the epicenter of the outbreak in China.

Result: Patient 1 was a 53-year-old man with hepatitis B virus-related cirrhosis, portal hypertension, and ascites. Though receiving intensive support, he died of irreversible multiple organ dysfunction syndrome 48 days after the onset of the illness. Patient 2 was a 75-year-old woman with a history of schistosomiasis-related cirrhosis, portal hypertension, and ascites. Her family members requested that invasive rescue measures not be undertaken, and she died of acute respiratory distress syndrome 40 days after presenting with COVID-19 infection. Patient 3 was an 87-year-old man with alcohol-related cirrhosis, portal hypertension, and esophageal variceal hemorrhage. He was discharged from the hospital 29 days after illness onset.

Conclusion: The case series raise the possibility that decompensated cirrhosis may be a risk factor for a poor outcome in patients with COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-020-10051-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242176PMC
July 2020

LINE-1 Methylation in Chronic HBV Infected Patients: Association with HCC, Gender and MTHFR C677T Polymorphism.

Clin Lab 2020 May;66(5)

Background: Polymorphism of methylene tetrahydrofolate reductase (MTHFR) C677T has been reported to be associated with HBV-related hepatocellular carcinoma (HCC) risk. However, the underlying mechanism remains elusive. DNA methylation has been suggested to be associated with HCC onset. MTHFR is the key enzyme in folic acid metabolism, thus, it influences the production of the main donor of methyl groups for DNA methylation. This study aimed to determine the association of global DNA methylation with MTHFR C677T polymorphism in chronic HBV infected patients, as well as its association with HCC and gender.

Methods: In all, 130 chronic hepatitis B (CHB) and 131 HBV-related HCC patients were enrolled in the study. The methylation level of long interspersed nuclear element-1 (LINE-1), the surrogate marker of global DNA methylation, and MTHFR C677T genotypes were determined.

Results: The HCC group showed significantly lower LINE-1 methylation than the CHB group (p = 0.016). Females were observed to have a markedly lower LINE-1 methylation level than males in both CHB and HCC groups (p = 0.000, p = 0.014, respectively). A significant relationship between MTHFR C677T polymorphism and LINE-1 methylation was observed in the CHB group (F = 5.985, p = 0.003). CT, TT, and CT + TT genotypes were significantly associated with lower LINE-1 methylation level compared with the CC genotype (p = 0.005, p = 0.018, p = 0.001, respectively). In addition, the association between MTHFR C677T and LINE-1 methylation was more significant in females (F= 5.036, p = 0.011) than in males (F = 3.083, p = 0.051); further, the association was significant in the subjects older than 60 years (F = 3.865, p = 0.028), but not in the subgroup aged less than 60 years (F = 2.496, p = 0.089).

Conclusions: LINE-1 methylation level in chronic HBV infected patients was associated with the occurrence of HBV-related HCC, gender, and MTHFR C677T polymorphism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7754/Clin.Lab.2019.190906DOI Listing
May 2020

Cinobufagin Triggers Defects in Spindle Formation and Cap-Dependent Translation in Liver Cancer Cells by Inhibiting the AURKA-mTOR-eIF4E Axis.

Am J Chin Med 2020 30;48(3):651-678. Epub 2020 Apr 30.

Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin City 300309, P. R. China.

Cinobufagin is a Na/K-ATPase (NKA) inhibitor with excellent anticancer effects to prolong the survival of patients. The purpose of the present study was to clarify the underlying mechanism of the anticancer effects of cinobufagin using overexpression or inhibition of aurora kinase A (AURKA) signaling. First, high expression of Na/K-ATPase alpha 1 subunit (ATP1A1) and AURAK resulted in increased malignant transformation in hepatocellular carcinoma (HCC) patients using the cancer genome atlas (TCGA) data and tissue samples. After treatment with cinobufagin, we successfully screened 202, 249, and 335 changing expression proteins in Huh-7 cells under normal, overexpression, and inhibition of AURKA using tandem mass tags (TMT)-labeled quantitative proteomics coupled to 2D liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatics analysis revealed that these molecules were closely associated with chromosome segregation, DNA damage, and regulation of translation processes. We further confirmed that cinobufagin induced DNA damage and chromosome segregation disorders and suppresses translational processing in oncogenes by decreasing the expression of AURKA, mechanistic target of rapamycin kinase (mTOR), p-mTOR, p-extracellular regulated protein kinases (ERK), eukaryotic translation initiation factor 4E (eIF4E), and p-eIF4E, while increasing the expression of p-eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) (S65, T37, T46, T45) and increasing the interaction between eIF4 and 4E-BP1. Our results suggested that cinobufagin performed an antitumor effects in liver cancer cells by inhibiting the AURKA-mTOR-eIF4E axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1142/S0192415X20500330DOI Listing
August 2020

Interleukin 22 is related to development and poor prognosis of hepatocellular carcinoma.

Clin Res Hepatol Gastroenterol 2020 11 20;44(6):855-864. Epub 2020 Mar 20.

Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin 300170, China. Electronic address:

Background And Aims: Immune response against hepatitis B virus (HBV) infection is an important risk factor for the development of hepatocellular carcinoma (HCC). Studies have reported that interleukin 22 (IL-22) exhibits both protective and pathological properties in liver diseases. Our aim was to explore the importance of IL-22 in the development of HCC, and to characterize the relationship between IL-22 levels and the prognosis of HCC.

Methods: Totally, 136 liver biopsy specimens from 46 patients with chronic hepatitis B (CHB), 37 with atypical hyperplasia (AH), 53 with HCC, patient-matched tumors and peritumoral surgical specimens from 56 HCC patients included in the study. The expression of IL-22 and CD8 was evaluated by immunochemistry. Corresponding serum samples were collected from 30 CHB, 30 AH, and 30 HCC patients. IL-22 expression was determined by an enzyme linked immunosorbent assay.

Results: Liver-infiltrating IL-22 cells increased in a stepwise manner from CHB to AH and HCC (CHB vs. AH, P=0.002; AH vs. HCC, P=0.010), whereas a decreasing trend was observed for CD8 T cells (CHB vs. AH, P=0.031; AH vs. HCC, P=0.652). Serum IL-22 levels also increased from CHB to AH and HCC (CHB vs. AH, P=0.024; AH vs. HCC, P=0.026). Tumor-infiltrating IL-22 cells and serum IL-22 were associated with histologic grade (P=0.024 and P=0.033). Additionally, CD8 T cells correlated with tumor size (P=0.032). Furthermore, the high intratumoral IL-22 cell group and high serum IL-22 group showed lower overall survival (OS; P=0.001, P=0.017) and disease-free survival (DFS; P=0.005, P<0.001). Multivariate analysis revealed that intratumoral IL-22 cells and serum IL-22 levels were independent prognostic factors for both OS and DFS.

Conclusions: These findings indicate that IL-22 promotes the progression of HCC in CHB patients. High tumor-infiltrating IL-22 cells and serum IL-22 levels are thought to be unfavorable prognostic indicators for HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2020.01.009DOI Listing
November 2020

The Effects of Matrine in Combination with Docetaxel on Castration-Resistant (Androgen-Independent) Prostate Cancer.

Cancer Manag Res 2019 2;11:10125-10133. Epub 2019 Dec 2.

Department of Urology, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, People's Republic of China.

Background: Matrine (MAT) exhibits higher efficacy of chemotherapy when it is combined with other chemotherapeutic drugs; however, the therapeutic efficacy of matrine in combination with docetaxel (DOC) for prostate cancer, or even androgen-independent prostate cancer, remains poorly understood and the underlying molecular mechanisms have not yet been clearly defined. In the present study, we investigated whether matrine combined with docetaxel can strengthen anti-cancer effect.

Methods: In this study, 7 groups were established, including (1) blank control group (cells). (2) 0.1 g/L MAT group, (3) 0.5 g/L MAT group, (4) 0.1 g/L MAT+ 50 μg/L DOC group, (5) 0.5 g/L MAT+ 50 μg/L DOC group, (6) 0.1 g/L MAT+ 100 μg/L DOC group, and (7) 0.5 g/L MAT+ 100 μg/L DOC group. MTS assay was performed to detect the anti-proliferative effects of each group on DU145 and PC-3 cells. At the same time, Transwell assay was performed to detect anti-migrative and anti-invasive effects of each group on DU145 and PC-3 cells. Biochemical colorimetric method and enzyme-linked immunosorbent assay were performed to detect the levels of LDH, IL-1β and IL-18 of each group on DU145 and PC-3 cells. Flow cytometry (FCM) assay was used to do the apoptosis analysis on DU145 and PC-3 cells of each group. At last, Western blot analysis was performed to investigate the expression levels of caspase1 in cells of each group. Statistical analyses were performed with SPSS 17.0 (SPSS Inc, USA) software, and one-way ANOVA and Fisher's exact test was taken.

Results: MTS assay showed that matrine combined with docetaxel could inhibit both DU145 and PC-3 cells' proliferation in a dose- and time-dependent manner. Transwell assay showed that matrine combined with docetaxel could inhibit both DU145 and PC-3 cells' migration and invasion in a dose- and time-dependent manner. The levels of LDH, IL-1β and IL-18 of matrine combined with docetaxel-treated DU145 and PC-3 cells were significantly increased, compared with the untreated control cells. Flow cytometry, as well as Annexin-V/PI staining, showed a significant and dose-dependent increase in the number of early, as well as late-stage apoptotic cells in both DU145 and PC-3 cells compared with the untreated control cells. Western blot analysis showed that matrine combined with docetaxel treatment led to the expression of caspase1 in both DU145 and PC-3 cells.

Conclusion: It may be more effective to use matrine in combination with docetaxel to treat androgen-resistant prostate cancer because matrine can help to affect proliferation, migration, invasion, apoptosis, metabolism, and have anti-inflammation effect on the tumor cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S213419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896908PMC
December 2019

Functional magnetic resonance imaging-based assessment of terlipressin octreotide on renal function in cirrhotic patients with acute variceal bleeding (CHESS1903): study protocol of a multicenter randomized controlled trial.

Ann Transl Med 2019 Oct;7(20):586

Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang 110000, China.

Background: Acute variceal bleeding is one of the critical complications in patients with liver cirrhosis. Severe renal vasoconstriction in consequence of low peripheral vascular resistance triggers the reduction of glomerular filtration rate (GFR), and thus induces acute kidney injury (AKI)/hepato-renal syndrome (HRS). Terlipressin and octreotide have been used in the management of cirrhotic patients with variceal bleeding. Also, terlipressin has been recommended as the international first-line pharmacological therapy for the treatment of HRS. In addition, the use of renal functional magnetic resonance imaging (fMRI) has become increasingly prevalent in research and clinical applications. However, the renal function-protective effect of terlipressin and octreotide and the value of fMRI in monitoring renal function remains unclear in patients with cirrhosis undergoing acute variceal bleeding.

Methods: This is a multicenter, randomized controlled trial (RCT). Participants will be 1:1 assigned randomly into either terlipressin or octreotide groups. Sixty participants with clinically and/or pathologically diagnosed cirrhosis and active gastroesophageal variceal bleeding (GVB) will be recruited in several sites in China. Participants will receive either the treatment of terlipressin or octreotide after assigned into each group. The primary end point for the trial is the renal function. The secondary end points are (I) renal perfusion; (II) renal blood oxygenation; (III) failure to control bleeding; (IV) intra-hospital rebleeding; (V) intra-hospital mortality; (VI) adverse events (AE); (VII) overall survival. Statistical analysis including multivariate Cox regression, Kaplan-Meier analysis with log-rank test, etc. will be conducted.

Discussion: The study will provide new insight into the protection of renal function in the process of the treatment of variceal bleeding in patients with cirrhosis.

Trial Registration Number: NCT04028323.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2019.09.141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861789PMC
October 2019

Robust trap effect in transition metal dichalcogenides for advanced multifunctional devices.

Nat Commun 2019 Sep 12;10(1):4133. Epub 2019 Sep 12.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, 100190, China.

Defects play a crucial role in determining electric transport properties of two-dimensional transition metal dichalcogenides. In particular, defect-induced deep traps have been demonstrated to possess the ability to capture carriers. However, due to their poor stability and controllability, most studies focus on eliminating this trap effect, and little consideration was devoted to the applications of their inherent capabilities on electronics. Here, we report the realization of robust trap effect, which can capture carriers and store them steadily, in two-dimensional MoSSe via synergistic effect of sulphur vacancies and isoelectronic selenium atoms. As a result, infrared detection with very high photoresponsivity (2.4 × 10 A W) and photoswitching ratio (~10), as well as nonvolatile infrared memory with high program/erase ratio (~10) and fast switching time, are achieved just based on an individual flake. This demonstration of defect engineering opens up an avenue for achieving high-performance infrared detector and memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-12200-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742650PMC
September 2019

Hierarchically heterostructured metal hydr(oxy)oxides for efficient overall water splitting.

Nanoscale 2019 Jun;11(24):11736-11743

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing 100190, China.

The design of highly efficient electrocatalysts containing non-precious metals is crucial for promoting overall water splitting in alkaline media. In particular, Janus catalysts simultaneously facilitating the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are desirable. Herein, we fabricated a unique hierarchical heterostructure via growing Ni4W6O21(OH)2·4H2O (denoted as Ni-W-O) nanosheets on NiMoO4 rods, which was indispensable for regulating the morphology of the Ni-W-O structure. This heterostructure of Ni-W-O/NiMoO4 could be utilized as an electrocatalyst to realize superior activity for overall water splitting in 1.0 M KOH. It substantially promoted overall water splitting with 1.6 V at 30 mA cm-2, outperforming numerous bifunctional electrocatalysts under the same conditions. Notably, the remarkable stability for continuously splitting water endowed this hierarchical heterostructure with potential applications on a large scale. This work emphasizes the effectively controlled growth of heterostructured non-noble-metal catalysts for energy-conversion reaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9nr02988eDOI Listing
June 2019

The anticancer effects of cinobufagin on hepatocellular carcinoma Huh‑7 cells are associated with activation of the p73 signaling pathway.

Mol Med Rep 2019 May 29;19(5):4119-4128. Epub 2019 Mar 29.

Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, P.R. China.

The Na+/K+‑ATPase inhibitor cinobufagin exhibits numerous anticancer effects on hepatocellular carcinoma (HCC) cells expressing wild‑type p53 via inhibition of aurora kinase A (AURKA) and activation of p53 signaling. However, the effects of cinobufagin on HCC cells expressing mutant p53 remain unclear. In the present study, the anticancer effects of cinobufagin were investigated on HCC Huh‑7 cells with mutant p53, and the effects of AURKA overexpression or inhibition on the anticancer effects of cinobufagin were analyzed. Viability, cell cycle progression and apoptosis of cells were determined using an MTT assay, flow cytometry and Hoechst 33342 staining, respectively. The expression levels of p53 and p73 signaling‑associated proteins were investigated via western blot analysis. The results demonstrated that the expression levels of AURKA, B‑cell lymphoma 2 (Bcl‑2), cyclin‑dependent kinase 1, cyclin B1, proliferating cell nuclear antigen and heterogeneous nuclear ribonucleoprotein K, as well as the phosphorylation of p53 and mouse double minute 2 homolog, were significantly decreased in Huh‑7 cells treated with 5 µmol/l cinobufagin for 24 h. Conversely, the expression levels of Bcl‑2‑associated X protein, p21, p53 upregulated modulator of apoptosis and phorbol‑12‑myristate‑13‑acetate‑induced protein 1, were significantly increased by cinobufagin treatment. Overexpression or inhibition of AURKA suppressed or promoted the anticancer effects of cinobufagin on Huh‑7 cells, respectively. These results indicated that cinobufagin may induce anticancer effects on Huh‑7 cells via the inhibition of AURKA and p53 signaling, and via the activation of p73 signaling, in an AURKA‑dependent manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2019.10108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471725PMC
May 2019

HCV core antigen is a useful predictor during pegylated-interferon/ribavirin therapy in patients with hepatitis C virus genotype 1b.

Medicine (Baltimore) 2019 Mar;98(10):e14795

Clinical Laboratory of Tianjin Third Central Hospital.

Enzyme immunoassays for quantifying hepatitis C virus (HCV) core antigen (Ag) have been proposed as an alternative to HCV RNA detection. The present study aimed to investigate the early kinetics of serum HCVcAg and its usefulness in predicting virological responses.The clinical data of 135 patients with chronic hepatitis C treated with pegylated interferon alpha (PEG-IFN-α) and ribavirin was retrospectively collected. The patients were grouped according to their treatment outcomes as follows: sustained virological response (SVR), nonsustained virological response (N-SVR), and relapse.Higher HCVcAg and HCV RNA levels were observed in patients in the N-SVR group than in the other groups at baseline. HCVcAg better predicted rapid virological response (RVR) compared with HCV RNA and had a predictive value similar to that of HCV RNA for SVR and early virological response. In the relapse group, HCV RNA decreased to 0 after 48 weeks, whereas HCVcAg was still detectable, indicating that HCVcAg more sensitively predicted relapse in antiviral therapy than HCV RNA.For patients treated with PEG-INF-α and ribavirin, HCVcAg may more sensitively predict relapse than HCV RNA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000014795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417632PMC
March 2019

Heterostructures Based on 2D Materials: A Versatile Platform for Efficient Catalysis.

Adv Mater 2019 Nov 31;31(45):e1804828. Epub 2018 Oct 31.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, 100190, China.

The unique structural and electronic properties of 2D materials, including the metal and metal-free ones, have prompted intense exploration in the search for new catalysts. The construction of different heterostructures based on 2D materials offers great opportunities for boosting the catalytic activity in electo(photo)chemical reactions. Particularly, the merits resulting from the synergism of the constituent components and the fascinating properties at the interface are tremendously interesting. This scenario has now become the state-of-the-art point in the development of active catalysts for assisting energy conversion reactions including water splitting and CO reduction. Here, starting from the theoretical background of the fundamental concepts, the progressive developments in the design and applications of heterostructures based on 2D materials are traced. Furthermore, a personal perspective on the exploration of 2D heterostructures for further potential application in catalysis is offered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.201804828DOI Listing
November 2019

CXCL12 modulates the radiosensitivity of cervical cancer by regulating CD44.

Mol Med Rep 2018 Dec 12;18(6):5101-5108. Epub 2018 Oct 12.

Department of Gynaecology and Obstetrics, Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China.

The aim of the present study was to investigate the regulation of stromal cell‑derived factor 1 (CXCL12) in the radioresistance of cervical cancer, which was upregulated in tumors in our previous study. A CCK‑8 assay was used to detect cell viability. Flow cytometry was used to measure cell apoptosis and the expression levels of CD44 and CXCR4. ELISA was performed to measure the expression level of CXCL12 protein and CXCL12 mRNA was detected by reverse transcription‑quantitative polymerase chain reaction assays. Cell viability and apoptosis were determined with or without treatment with CXCL12 small interfering (si)RNA to examine the function of CXCL12 in Hela cells. The expression level of CD44 antigen (CD44) and C‑X‑C chemokine receptor type 4 (CXCR4) were measured using flow cytometry in the presence of CXCL12 and irradiation. In the present study, it was demonstrated that inhibition of CXCL12 reduced cell viability and increased cellular apoptosis in Hela cells treated with irradiation. Following treatment with CXCL12 siRNA, the expression level of CD44 was downregulated and the expression level of CXCR4 was upregulated. This effect of regulation additionally occurred in the presence of irradiation. In conclusion, the present data demonstrated that CXCL12 served an important role in the radioresistance of cervical cancer, suggestinh a novel therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2018.9554DOI Listing
December 2018