Publications by authors named "Xiangcheng Li"

77 Publications

PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma.

Front Oncol 2021 26;11:607021. Epub 2021 Feb 26.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Proteasome 26S subunit ATPase 2 (PSMC2) plays a pathogenic role in various cancers. However, its function and molecular mechanism in hepatocellular carcinoma (HCC) remain unknown. In this study, tissue microarray (TMA) analysis showed that PSMC2 is highly expressed in HCC tumors and correlates with poor overall and disease-free survival in HCC patients. Multivariate Cox regression analysis revealed that PSMC2 is an independent prognostic factor for HCC patients. Furthermore, our results showed that PSMC2 knockdown inhibited cell proliferation and suppressed tumorigenesis . Knockdown of PSMC2 increased the expression of p21 and therefore decreased the expression of cyclin D1. Dual-luciferase reporter assays indicated that depletion of PSMC2 significantly enhanced the promoter activity of p21. Importantly, PSMC2 knockdown-induced phenotypes were also rescued by downregulation of P21. Taken together, our data suggest that PSMC2 promotes HCC cell proliferation and cell cycle progression through the p21/cyclin D1 signaling pathway and could be a promising diagnostic and therapeutic target for HCC patients.
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http://dx.doi.org/10.3389/fonc.2021.607021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952995PMC
February 2021

Development of cisplatin-loaded hydrogels for trans-portal vein chemoembolization in an orthotopic liver cancer mouse model.

Drug Deliv 2021 Dec;28(1):520-529

Department of Surgery, HKU-SZH and Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Transarterial chemoembolization is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). This study evaluated the anti-tumor effect of the semi-interpenetrating network (IPN) hydrogel as a novel embolic material for trans-portal vein chemoembolization (TPVE) . A nude mice orthotopic HCC model was established, followed by TPVE using IPN hydrogel loaded with or without cisplatin. Portal vein blockade was visualized by MRI and the development of tumor was monitored by IVIS Spectrum Imaging. Tumor proliferation and angiogenesis were evaluated by Ki67 and CD34 staining respectively. Intra-tumor caspase 3, Akt, ERK1/2, and VEGF activation were detected by Western Blot. F-FMISO uptake was evaluated by microPET-MRI scanning. IPN hydrogel first embolized the left branch of portal vein within 24 hours and further integrated into the intra-tumor vessels during 2 weeks after the treatment. Mice treated with cisplatin-loaded hydrogels exhibited a significant decrease in tumor growth, along with lower plasma AFP levels as compared to hydrogel-treated and untreated tumor-bearing mice. By Ki67 and CD34 staining, the TPVE with IPN hydrogel suppressed tumor proliferation and angiogenesis. In addition, increased tumor apoptosis shown by up-regulation of caspase 3 with decreased expressions of tumor cell survival indicators Akt and ERK1/2 were observed in the treatment groups. Consistent with the decreased expression of VEGF after TPVE, hypoxia level in the tumor was also reduced as indicated by F-FMISO uptake level. IPN hydrogel-based TPVE significantly suppressed the tumor development by regulating intra-tumor angiogenesis and cell survival in an orthotopic HCC mouse model, suggesting a viable embolic agent for transarterial chemoembolization.
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http://dx.doi.org/10.1080/10717544.2021.1895908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946021PMC
December 2021

Photocatalytic Activity of Magnetic Nano-β-FeOOH/FeO/Biochar Composites for the Enhanced Degradation of Methyl Orange Under Visible Light.

Nanomaterials (Basel) 2021 Feb 18;11(2). Epub 2021 Feb 18.

The State Key Laboratory of Refractories and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, China.

A novel nano-β-FeOOH/FeO/biochar composite with enhanced photocatalytic performance and superparamagnetism was successfully fabricated via an environmentally friendly one-step method. The structural properties of the prepared composite were characterized by scanning electron microscopy, transmission electron microscopy, energy-dispersive spectroscopy, X-ray photoelectron spectroscopy, and a vibrating sample magnetometer. The XPS spectrum of the as-prepared composites confirmed the presence of Fe-O-C bonds between β-FeOOH and biochar, which could be conducive to transfer photo-generated electrons. UV-vis spectroscopy confirmed the existence of an electron-hole connection between β-FeOOH and biochar, which promoted the rapid interface transfer of photogenerated electrons from β-FeOOH to biochar. These novel structures could enhance the response of biochar to accelerate the photoelectrons under visible light for more free radicals. Electron spin resonance analysis and free radical quenching experiments showed that •OH was the primary active species in the photodegradation process of methyl orange by nano-β-FeOOH/FeO/biochar. In the synergistic photocatalytic system, β-FeOOH/FeO/biochar exhibited excellent catalytic activity for the degradation of azo dye (methyl orange), which is 2.03 times higher than that of the original biochar, while the surface area decreased from 1424.82 to 790.66 m·g. Furthermore, β-FeOOH/FeO/biochar maintained a stable structure and at least 98% catalytic activity after reuse, and it was easy to separate due to its superparamagnetism. This work highlights the enhanced photocatalytic performance of β-FeOOH/FeO/biochar material, which can be used in azo dye wastewater treatment.
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http://dx.doi.org/10.3390/nano11020526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923089PMC
February 2021

Development and external validation of a nomogram for predicting the effect of tumor size on cancer-specific survival of resected gallbladder cancer: a population-based study.

Int J Clin Oncol 2021 Mar 5. Epub 2021 Mar 5.

Key Laboratory on Living Donor Transplantation, Ministry of Health, Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu, China.

Background: The impact of tumor size on account of the long-term survival results in gallbladder cancer (GBC) patients has been controversial. It is urgent necessary to identify the optimal cut-off value of tumor size in resected GBC, and we attempted to integrate tumor size with other prognostic factors into a prognostic nomogram to predict the cancer-specific survival (CSS) of GBC patients.

Methods: 1639 patients with resected GBC were extracted from the Surveillance, Epidemiology and End Results (SEER) database. X-tile program was used to identify the optimal cut-off value of tumor size. A nomogram including tumor size was established to predict 1-, 3- and 5-year CSS based on the independent risk factors chosen by univariate and multivariable cox analyses. The precision of the nomogram for predicting survival was validated with Harrell's concordance index (C-index), calibration curves, and receiver operating characteristic curve (ROC) internally and externally.

Results: Patients with GBC were classified into 1-13 mm, 14-63 mm and 64 mm subgroup based on the optimal cut-off for tumor size in terms of CSS. The nomogram according to the independent factors was well calibrated and displayed better discrimination power than 7th tumor-node-metastasis (TNM) stage systems.

Conclusions: The results demonstrated that increased tumor size is closely associated with the worse CSS. Our novel nomogram, which outperforms the conventional TNM staging system, showed satisfactory accuracy and clinically practicality for predicting the outcome of resected GBC patients.
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http://dx.doi.org/10.1007/s10147-021-01891-2DOI Listing
March 2021

Circular RNA circARPP21 Acts as a Sponge of miR-543 to Suppress Hepatocellular Carcinoma by Regulating LIFR.

Onco Targets Ther 2021 5;14:879-890. Epub 2021 Feb 5.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People's Republic of China.

Background: A large body of evidence has shown that circular RNAs (circRNAs) play a significant role in the progression of some malignant cancers, including hepatocellular carcinoma (HCC). However, the complex mechanism of circRNAs in hepatocellular carcinoma has not been clarified.

Methods: We identified circRNAs by microarray analysis and quantitative real-time polymerase chain reaction (RT-qPCR). We also carried out bioinformatics analysis, luciferase reporter assays, and RNA pull-down assays to define the relationship between microRNA (miR)-543 and circARPP21. Through silencing and overexpression of circARPP21, we investigated the effects of circARPP21 on proliferation, migration, and invasion abilities of HCC cells in vitro and in vivo.

Results: In this study, we found that a novel circRNA, circARPP21 (hsa_circ_0123629), exerts a strong effect on HCC progression. Reduced expression of circARPP21 in HCC patients is correlated with larger tumor size, higher tug-lymph node metastasis (TNM) stage, and poor prognosis as indicated by elevated levels of alpha-fetoprotein (AFP). Conversely, higher expression of circARPP21 can increase leukemia inhibitory factor receptor (LIFR) expression by sponging miR-543. Finally, overexpression of miR-543 can reverse the anti-proliferation and anti-metastasis effects of circARPP21.

Conclusion: The circARPP21/miR-543/LIFR axis suppresses the proliferation, invasion, and migration of hepatocellular carcinoma cells. In addition, circARPP21 can serve as a biomarker in HCC, thus offering a potential new approach to HCC therapy.
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http://dx.doi.org/10.2147/OTT.S283026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874301PMC
February 2021

Screening and identification of haptoglobin showing its important role in pathophysiological process of gallbladder carcinoma.

Gene 2021 Apr 12;776:145429. Epub 2021 Jan 12.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, and Changzhou Institute of Innovation and Development, Nanjing Normal University, Nanjing 210023, China. Electronic address:

Gallbladder cancer (GBC) with poor prognosis has been a major cause of cancer-related deaths worldwide. In this study, we aimed to screen and identify crucial genes in GBC through integrative analysis of multiple datasets and further experimental validation. A candidate crucial gene, up-regulated haptoglobin (HP), was firstly screened, and then further analysis and validation mainly focused on whether higher enrichment level of HP was responsible for pathophysiological process of GBC. HP was found with diverse expression patterns in various cancer types, and the dynamic expression patterns indicated its spatiotemporal characteristics in different tissues and disease stages, implicating its role in multiple biological processes. Further experimental validation showed that HP could promote the GBC-SD cell proliferation, migration and invasion, implying its role in pathophysiological process of GBC. HP may have a crucial role in occurrence and development of GBC, and it provides possibility as a potential biomarker or target in cancer prognosis and treatment.
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http://dx.doi.org/10.1016/j.gene.2021.145429DOI Listing
April 2021

Microstructure and Properties of Mechanical Alloying Al-Zr Coating by High Current Pulsed Electron Beam Irradiation.

Nanomaterials (Basel) 2020 Nov 30;10(12). Epub 2020 Nov 30.

School of Materials Science and Engineering, Jiangsu University, Zhenjiang 212013, China.

The "HOPE-I" type high-current pulsed electron beam (HCPEB) equipment was used to irradiate the pure aluminum material with Zr coating preset by ball milling to realize the alloying of a Zr-Al coating surface. The microstructure and phase analysis were conducted by XRD, SEM, and TEM. The experimental results show that after Zr alloying on the Al surface by HCPEB, a layer of 15 μm was formed on the surface of the sample, which was mainly composed of Zr and Al-Zr intermetallic compounds. A large number of AlZr (Ll2) particles was uniformly distributed in the alloyed layer, and the Al grains were obviously refined. In addition, the surface hardness and corrosion resistance of the samples were improved significantly after HCPEB irradiation.
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http://dx.doi.org/10.3390/nano10122398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759798PMC
November 2020

Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial.

J Immunother Cancer 2020 11;8(2)

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Background: Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.

Methods: In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m) and oxaliplatin (85 mg/m). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.

Results: 54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).

Conclusion: Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.

Trial Registration Number: NCT03486678.
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http://dx.doi.org/10.1136/jitc-2020-001240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656907PMC
November 2020

Development and external validation of a nomogram for predicting the effect of tumor size on survival of patients with perihilar cholangiocarcinoma.

BMC Cancer 2020 Oct 30;20(1):1044. Epub 2020 Oct 30.

Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of liver surgery, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu Province, China.

Background: The effect of tumor size on account of long-term survival results in perihilar cholangiocarcinoma (PCCA) patients has remained a controversial debate. It is urgent necessary to identify the optimal cutoff value of tumor size in PCCA and integrate tumor size with other prognostic factors into a nomogram to improve the predictive accuracy of prognosis of patients with PCCA.

Methods: Three hundred sixty-three PCCA patients underwent surgical resection were extracted from the Surveillance, Epidemiology and End Results (SEER) database. X-tile program was used to identify the optimal cutoff value of tumor size. A nomogram including tumor size was established to predict 1-, 3- and 5-year cancer-specific survival (CSS) based on the independent risk factors chosen by Kaplan-Meier methods and multivariable cox regression models. The precision of the nomogram for predicting survival was validated internally and externally.

Results: PCCA patients underwent surgical resection were classified into 1-19 mm, 20-33 mm and ≥ 34 mm subgroups based on the optimal cutoff for tumor size in terms of CSS. And we noticed that more larger tumor size group had worse tumor grade, advanced T stage, more positive regional lymph nodes and more frequent vascular invasion. The nomogram according to the independent factors was well calibrated and displayed better discrimination power than 7th Tumor-Node-Metastasis (TNM) stage systems.

Conclusions: The results demonstrated that the larger tumor size of PCCA was, the worse survival would be. The proposed nomogram, which outperforms the conventional TNM staging system, showed relatively good performance and could be considered as convenient individualized predictive tool for prognosis of PCCA patients.
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http://dx.doi.org/10.1186/s12885-020-07501-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596930PMC
October 2020

An updated incidence trends of soft-tissue sarcoma and cancer-specific survival of patients with primary soft-tissue sarcoma of liver: a population-based study.

Expert Rev Gastroenterol Hepatol 2020 Nov 13:1-10. Epub 2020 Nov 13.

Key Laboratory on Living Donor Transplantation, Ministry of Health, Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

: This study aimed to evaluate and update incidence trends of soft-tissue sarcoma (STS) and to develop a nomogram to predict cancer-specific survival (CSS) in patients diagnosed with primary STS of the liver.: Patients with hepatic STS were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Joinpoint regression analyses were performed to assess the incidence trends of STS. A nomogram was developed based on the independent risk factors chosen by Cox regression models. The calibration curve, area under the receiver operating characteristic curve (AUC), C-index, and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram.: The incidence of STS increased between 1994 and 2012. There was a sudden decline in the incidence of STS from 2013. The incidence of STS was different in distinct races and genders. The nomogram for predicting the CSS of hepatic STS according to the independent factors was well calibrated and it displayed optimal discrimination power.: This study highlights that age, sex, tumor size, quality of surgery, and histologic subtypes may contribute to the prognosis of hepatic STS, and STS may be etiologically distinct and should be considered separately in different races and genders.
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http://dx.doi.org/10.1080/17474124.2021.1842193DOI Listing
November 2020

Hypoxia-induced hsa_circ_0000826 is linked to liver metastasis of colorectal cancer.

J Clin Lab Anal 2020 Sep 7;34(9):e23405. Epub 2020 Jul 7.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: hsa_circ_0000826 has been previously linked to CRC through the competing endogenous RNA network; however, the upstream driver of hsa_circ_0000826 elevation remains unknown. In this study, we aim to elucidate the effect of hypoxia-induced hsa_circ_0000826 on CRC tumorigenesis and metastasis.

Methods: RNA scope assay was used to evaluate the expression of hsa_circ_0000826 in CRC cells under hypoxia condition. The effects of hsa_circ_0000826 on phenotypes of CRC cells were evaluated through cell migration and invasion assay. The nude, AOM-DSS model mice and APC mice were used to investigate the relationship between circ_0000826, hypoxia, and CRC in mice. A total of 100 CRC tissue samples, as well as the paired adjacent tissues, were collected, and qRT-PCR assay was used to detect the expression of hsa_circ_0000826 in these samples.

Results: Hypoxia-induced hsa_circ_0000826 overexpression can increase the malignant phenotypes, tumor formation, and metastasis capability of CRC cells in vitro. mmu_circ_0000826 levels were significantly increased in the CRC tissues from AOM-DSS and APC mice model under hypoxia conditions. Further, the hypoxia-induced upregulation of mmu_circ_0000826 can also promote CRC tumorigenesis and liver metastasis in vivo. The expression of hsa_circ_0000826 in serum was significantly increased in CRC tissues in 100-pair of CRC and according to the adjacent normal tissues by qRT-PCR assays. Moreover, the expression levels of hsa_circ_0000826 in serum of patient with liver metastasis were significantly increased than those without metastasis.

Conclusion: Our results suggested that hsa_circ_0000826 was induced by the hypoxia in CRC, which can be a potential biomarker of CRC liver metastasis.
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http://dx.doi.org/10.1002/jcla.23405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521269PMC
September 2020

M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring α β Integrin to Tumor Cells.

Hepatology 2021 Apr;73(4):1365-1380

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background And Aims: The development and progression of hepatocellular carcinoma (HCC) is dependent on its local microenvironment. Tumor-associated macrophages (TAMs) are deemed a key factor for the tumor microenvironment and attribute to contribute to tumor aggressiveness. However, the detailed mechanism underlying the pro-metastatic effect of TAMs on HCC remains undefined.

Approach And Results: The present study proved that TAMs were enriched in HCC. TAMs were characterized by an M2-polarized phenotype and accelerated the migratory potential of HCC cells in vitro and in vivo. Furthermore, we found that M2-derived exosomes induced TAM-mediated pro-migratory activity. With the use of mass spectrometry, we identified that integrin, α β (CD11b/CD18), was notably specific and efficient in M2 macrophage-derived exosomes (M2 exos). Blocking either CD11b and/or CD18 elicited a significant decrease in M2 exos-mediated HCC cell metastasis. Mechanistically, M2 exos mediated an intercellular transfer of the CD11b/CD18, activating the matrix metalloproteinase-9 signaling pathway in recipient HCC cells to support tumor migration.

Conclusions: Collectively, the exosome-mediated transfer of functional CD11b/CD18 protein from TAMs to tumor cells may have the potency to boost the migratory potential of HCC cells, thus providing insights into the mechanism of tumor metastasis.
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http://dx.doi.org/10.1002/hep.31432DOI Listing
April 2021

IL-17a exacerbates hepatic ischemia-reperfusion injury in fatty liver by promoting neutrophil infiltration and mitochondria-driven apoptosis.

J Leukoc Biol 2020 11 12;108(5):1603-1613. Epub 2020 Jun 12.

Department of Surgery, HKU-SZH & Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Hepatic ischemia-reperfusion (IR) injury is a critical issue during liver transplantation (LT). Recent studies have demonstrated that IL-17a contributes to IR injury and steatohepatitis. However, the underlying mechanism is not understood. This study aimed to examine the role of IL-17a on hepatic IR injury in fatty liver and to investigate the underlying mechanisms. The correlation between serum IL-17a levels and liver function was analyzed in LT patients receiving fatty (n = 42) and normal grafts (n = 44). Rat LT model was applied to validate the clinical findings. IL-17a knockout (KO) and wild-type mice were fed with high-fat diets to induce fatty liver and subjected to hepatic IR injury with major hepatectomy. Frequency of circulating neutrophils and IL-17a expression on PBMCs were analyzed by flow cytometry. Mitochondrial outer membrane permeabilization (MOMP) was examined by a living intravital image system. Serum IL-17a was elevated after human LT, especially with fatty grafts. The aspartate aminotransferase and alanine transaminase levels were increased in recipients with fatty grafts compared with normal grafts. In rat LT model, the intragraft IL-17a expression was significantly higher in fatty grafts than normal ones post-LT. KO of IL-17a in mice notably attenuated liver damage after IR injury in fatty liver, characterized by better-preserved liver architecture, improved liver function, and reduced neutrophil infiltration. MOMP triggered cell death after hepatic IR injury in a caspase-independent way via IL-17a/NF-κB signaling pathway. KO of IL-17a protected the fatty liver against IR injury through the suppression of neutrophil infiltration and mitochondria-driven apoptosis.
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http://dx.doi.org/10.1002/JLB.3MA0520-716RDOI Listing
November 2020

The lncRNA Gm15622 stimulates SREBP-1c expression and hepatic lipid accumulation by sponging the miR-742-3p in mice.

J Lipid Res 2020 07 30;61(7):1052-1064. Epub 2020 Mar 30.

Department of Bioinformatics, School of Geographic and Biologic Information, Nanjing University of Posts and Telecommunications, Nanjing 210023, China.

Excessive lipid deposition is a hallmark of NAFLD. Although much has been learned about the enzymes and metabolites involved in NAFLD, few studies have focused on the role of long noncoding RNAs (lncRNAs) in hepatic lipid accumulation. Here, using in vitro and in vivo models of NAFLD, we found that the lncRNA Gm15622 is highly expressed in the liver of obese mice fed a HFD and in murine liver (AML-12) cells treated with free fatty acids. Investigating the molecular mechanism in the liver-enriched expression of Gm15622 and its effects on lipid accumulation in hepatocytes and on NAFLD pathogenesis, we found that Gm15622 acts as a sponge for the microRNA miR-742-3p. This sponging activity increased the expression of the transcriptional regulator SREBP-1c and promoted lipid accumulation in the liver of the HFD mice and AML-12 cells. Moreover, further results indicated that metformin suppresses Gm15622 and alleviates NAFLD-associated lipid deposition in mice. In conclusion, we have identified an lncRNA Gm15622/miR-742-3p/SREBP-1c regulatory circuit associated with NAFLD in mice, a finding that significantly advances our insight into how lipid metabolism and accumulation are altered in this metabolic disorder. Our results also suggest that Gm15622 may be a potential therapeutic target for managing NAFLD.
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http://dx.doi.org/10.1194/jlr.RA120000664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328049PMC
July 2020

Screening and identification of genes associated with cell proliferation in cholangiocarcinoma.

Aging (Albany NY) 2020 02 10;12(3):2626-2646. Epub 2020 Feb 10.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Cholangiocarcinoma (CCA), an aggressive tumor with poor prognosis, is a malignant cancer with increasing incidence and mortality rates. It is important to survey crucial genes in CCA to find and design potential drug targets, especially for those genes associated with cell proliferation that is a key biological process in tumorgenesis. Herein, we surveyed genes associated with cell proliferation via a comprehensive pan-cancer analysis. Candidate genes were further analyzed using multiple approaches, including cross-analysis from diverse molecular levels, examination of potential function and interactions, and additional experimental validation. We primarily screened 15 potential genes based on 11 validated genes, and these 26 genes were further examined to delineate their biological functions and potential roles in cancer treatment. Several of them were involved synthetically lethal genetic interactions, especially for , , and , indicating their potential roles in drug design and cancer treatment. Further experimental validation indicated that some genes were significantly upregulated in several cancer cell lines, implying their important roles in tumorigenesis. Our study identifies some genes associated with cell proliferation, which may be potential future targets in molecular targeted therapy.
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http://dx.doi.org/10.18632/aging.102766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041743PMC
February 2020

Autophagy Suppression Accelerates Apoptosis Induced by Norcantharidin in Cholangiocarcinoma.

Pathol Oncol Res 2020 Jul 14;26(3):1697-1707. Epub 2019 Oct 14.

Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 GuangZhou Road, Nanjing, 210029, Jiangsu, China.

Norcantharidin is a cantharidin demethylated analog with antitumor effects in many tumors, including cholangiocarcinoma. Autophagy suppression is known to increase chemosensitivity in cholangiocarcinoma. This study aimed to determine whether autophagy suppression accelerates apoptosis induced by norcantharidin in human cholangiocarcinoma cells. The human cholangiocarcinoma cell line QBC939 was incubated in RPMI 1640 medium with or without norcantharidin. Autophagy was induced using HBSS media with Ca and Mg supported by 10 mM HEPES or suppressed by treatment with 3-MA or transfection with siRNA against Atg5. The comparison was drawn between these conditions in mitochondrial membrane potential disturbance, the levels of reactive oxygen species (ROS), apoptotic proteins, and apoptosis. Cholangiocarcinoma cell apoptosis was accelerated by norcantharidin. Autophagy suppression up-regulated norcantharidin's pro-apoptotic effect, but autophagy induction weakened it. As apoptosis was accelerated, ROS production was up-regulated. Bax protein expression, cytochrome c levels and localization, mitochondrial membrane disturbance, and the levels of caspase-9, caspase-3, and cleaved PARP were higher when autophagy was suppressed, and all of those were down-regulated when autophagy was induced. To sum up, it was found that norcantharidin induced cholangiocarcinoma cell death, and autophagy suppression enhanced the pro-apoptotic action of norcantharidin, which appears to involve the mitochondrial apoptosis pathway activation and ROS generation.
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http://dx.doi.org/10.1007/s12253-019-00719-9DOI Listing
July 2020

Long-term survival after anterior approach right hepatectomy combined with inferior vena cava thrombectomy using trans-diaphragmatic intrapericardial inferior vena cava occlusion: a case report and review of the literature.

BMC Surg 2019 Aug 28;19(1):122. Epub 2019 Aug 28.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.

Background: Presence of inferior vena cava tumor thrombosis (IVCTT) is an unfavorable factor to prognosis for patients with hepatocellular carcinoma (HCC).

Case Presentation: Herein we report a case of HCC with IVC tumor thrombosis extending from the right hepatic vein (RHV) to the IVC, but it had not infiltrated the right atrium. Anterior approach right hepatectomy combined with IVC thrombectomy using trans-diaphragmatic IVC occlusion was performed for this patient. The patient is alive with disease-free at 32 months after treatment. A literature review was also performed. This case was demonstrated with the details and concepts of surgery.

Conclusion: This case suggested that surgical resection of HCC involving the IVC, but still outside the right atrium (RA), could offer satisfactory surgical outcomes in selected patients.
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http://dx.doi.org/10.1186/s12893-019-0568-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712705PMC
August 2019

Regional lymphadenectomy vs. extended lymphadenectomy for hilar cholangiocarcinoma (Relay-HC trial): study protocol for a prospective, multicenter, randomized controlled trial.

Trials 2019 Aug 23;20(1):528. Epub 2019 Aug 23.

Department of Biliary-Pancreatic Surgery, Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Pujian Road 160, Shanghai, 200127, People's Republic of China.

Background: The prognostic benefits and safety of extended lymphadenectomy for hilar cholangiocarcinoma remain uncertain. The available evidence is still insufficient concerning its retrospective aspect. The aim of this study is to explore the clinical effect and safety of extended lymphadenectomy compared to regional lymphadenectomy in patients with hilar cholangiocarcinoma.

Methods: The Relay-HC trial is a prospective, multicenter, and randomized controlled trial. Seven hundred and thirty-four eligible patients with resectable perihilar cholangiocarcinoma across 15 tertiary hospitals in China will be randomly assigned (1:1) to receive either regional lymphadenectomy or extended lymphadenectomy. The primary objective is to determine the overall survival after the two approaches. Secondary objectives of the study include the evaluation of perioperative mortality, postoperative complication, and disease-free survival. This study has been approved by the ethics committee of each participating hospital.

Discussion: The Relay-HC trial is designed to investigate the prognostic benefits and safety of expanded lymphadenectomy for hilar cholangiocarcinoma. Currently, it has never been investigated in a prospective randomized controlled clinical trial.

Trial Registration: Chinese Clinical Trial Registry (ChiCTR), ChiCTR1800015688 . Registered on 15 April 2018.
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http://dx.doi.org/10.1186/s13063-019-3605-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708245PMC
August 2019

Numerical Simulation on In-plane Deformation Characteristics of Lightweight Aluminum Honeycomb under Direct and Indirect Explosion.

Materials (Basel) 2019 Jul 10;12(14). Epub 2019 Jul 10.

College of Liberal Arts and Science, National University of Defense Technology, Changsha 410073, China.

Lightweight aluminum honeycomb is a buffering and energy-absorbed structure against dynamic impact and explosion. Direct and indirect explosions with different equivalent explosive masses are applied to investigate the in-plane deformation characteristics and energy-absorbing distribution of aluminum honeycombs. Two finite element models of honeycombs, i.e., rigid plate-honeycomb-rigid plate (RP-H-RP) and honeycomb-rigid plate (H-RP) are created. The models indicate that there are three deformation modes in the direction for the RP-H-RP, which are the overall response mode at low equivalent explosive masses, transitional response mode at medium equivalent explosive masses, and local response mode at large equivalent explosive masses, respectively. Meanwhile, the honeycombs exhibit two deformation modes in the direction, i.e., the expansion mode at low equivalent explosive masses and local inner concave mode at large equivalent explosive masses, respectively. Interestingly, a counter-intuitive phenomenon is observed on the loaded boundary of the H-RP. Besides, the energy distribution and buffering capacity of different parts on the honeycomb models are discussed. In a unit cell, most of the energy is absorbed by the edges with an edge thickness of 0.04 mm while little energy is absorbed by the other bilateral edges. For the buffering capacity, the honeycomb in the direction behaves better than that in the direction.
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http://dx.doi.org/10.3390/ma12142222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679438PMC
July 2019

Long noncoding RNA DDX11-AS1 epigenetically represses LATS2 by interacting with EZH2 and DNMT1 in hepatocellular carcinoma.

Biochem Biophys Res Commun 2019 07 13;514(4):1051-1057. Epub 2019 May 13.

Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 201129, China. Electronic address:

Long noncoding RNAs (lncRNAs), a group of transcripts without protein coding potential, have been reported to play critical roles in progression of hepatocellular carcinoma (HCC). However, the biological role of DDX11-AS1 in HCC is not clear. In this study, we found that DDX11-AS1 expression was dramatically higher in HCC tissues and cell lines. Higher DDX11-AS1 expression predicted poor overall survival of patients. Functionally, the proliferation, cell cycle progression, migration, and invasion of HCC cells were inhibited by DDX11-AS1 silencing, while promoted by ectopic expression of DDX11-AS1. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays validated that DDX11-AS1 suppressed LATS2 expression by interacting with EZH2 and DNMT1 in HCC cells. Knockdown of DDX11-AS1 increased the mRNA and protein levels of LATS2. Overexpression of LATS2 abolished the promotive effect of DDX11-AS1 on cell growth and invasion. Besides, DDX11-AS1 promoted tumor formation in vivo. The mRNA levels of LATS2 were markedly decreased in tumor tissues and negatively correlated with DDX11-AS1 expression. Taken together, our data indicated that DDX11-AS1 may be a novel oncogene in hepatocarcinogenesis by repressing LATS2, providing a potential therapeutic target for HCC treatment.
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http://dx.doi.org/10.1016/j.bbrc.2019.05.042DOI Listing
July 2019

Knockdown of tripartite motif 59 (TRIM59) inhibits proliferation in cholangiocarcinoma via the PI3K/AKT/mTOR signalling pathway.

Gene 2019 May 27;698:50-60. Epub 2019 Feb 27.

Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, China; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Jiangsu Province, China; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu Province, China. Electronic address:

Aim: We analysed multiple microarray datasets in the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) DataSets for messenger RNAs (mRNAs) whose expression is apparently increased in human cholangiocarcinoma (CCA) samples, compared with that in the adjacent normal biliary epithelial tissue. The results revealed that the expression of tripartite motif-containing 59 (TRIM59) was significantly increased in the CCA tissue samples. TRIM59 is a member of the tripartite motif (TRIM) protein family, which contains a highly conserved N-terminal-an interesting new gene (RING) domain regulating transcriptional factors and tumorigenesis. In the present study, we investigated the effects of TRIM59 expression on tumour growth in CCA.

Materials And Methods: After analyzing the microarray datasets from the TCGA database and GEO DataSets, we screened out 291 target genes, which are significantly overexpressed in CCA tissues, and TRIM59 was one of them. The quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were performed to determine the expression of TRIM59 in CCA tissues (n = 65) and cell lines. Kaplan-Meier survival analysis was conducted to assess the prognosis of TRIM59 in patients with CCA. A specific siRNA (siRNA-1008) was used to inhibit the expression of TRIM59 in HCCC9810 and HUCCT1 cell lines. The effects of TRIM59 silencing on cell proliferation were assessed by the CCK-8, colony-formation, and EDU incorporation assays. Furthermore, the effects of TRIM59 knockdown on cell apoptosis and cell cycle were determined by flow cytometry. The in vivo effects were evaluated using a mouse tumorigenic model. Western blotting was also performed to verify the relationship between knockdown of TRIM59 and activation of the PI3K/AKT/mTOR pathway.

Results: TRIM59 was highly expressed in CCA tissues. The knockdown of TRIM59 obviously reduced the proliferation and colony formation abilities of CCA cells in vitro and in vivo. Furthermore, the cell apoptosis analysis results showed that TRIM59 silencing apparently promoted CCA cell apoptosis by the mitochondrial pathway. Our preliminary results indicate that the down-regulation of TRIM59 levels might restrict the PI3K/AKT/mTOR signalling pathway.

Conclusions: Our study revealed that TRIM59 is up-regulated in CCA tissues and cell lines and promoted CCA cell proliferation, possibly by affecting the PI3K/AKT/mTOR signalling pathway.
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http://dx.doi.org/10.1016/j.gene.2019.02.044DOI Listing
May 2019

Inhibition of autophagy enhances cinobufagin‑induced apoptosis in gastric cancer.

Oncol Rep 2019 Jan 31;41(1):492-500. Epub 2018 Oct 31.

Department of Oncological Surgery, Xuzhou City Central Hospital, The Affiliated Hospital of the Southeast University Medical School (Xuzhou), The Tumor Research Institute of Southeast University (Xuzhou), Xuzhou, Jiangsu 221009, P.R. China.

Cinobufagin is a cardiotoxic bufanolide steroid secreted by the Asiatic toad Bufo gargarizans. Cinobufagin is one of the active ingredients in the anticancer Chinese medicine called Chan Su, which was demonstrated to be an effective treatment for gastric cancer. Increasing evidence shows that inhibition of autophagy has a pro‑apoptotic effect on human gastric cancer cells. The aim of the present study was to investigate the relationship between cinobufagin, autophagy and apoptosis in gastric cancer. Autophagy was induced or inhibited in the human gastric cancer cell line SGC‑7901 by incubation in HBSS media or by treatment with 3‑methyladenine or ATG5 siRNA, respectively. Following treatment, the levels of apoptosis, apoptotic proteins, reactive oxygen species (ROS), and mitochondrial membrane potential were compared between the conditions. As anticipated, we found that cinobufagin increased apoptosis in SGC‑7901 cells. Notably, inhibition of autophagy, monitored by the absence of the autophagosome marker LC3‑II, also enhanced cell apoptosis. This effect was reversed when autophagy was induced by incubation in HBSS media. Enhanced expression of pro‑apoptotic indicators, including BAX, cytosolic cytochrome c, cleaved PARP, caspase‑3 and caspase‑9, was detected when autophagy was suppressed. Increased pro‑apoptotic protein expression was accompanied by disrupted mitochondrial membrane potential and elevated ROS production. Altogether, these data suggest that inhibition of autophagy enhances the anticancer action of cinobufagin through increased apoptosis of gastric cancer cells. Moreover, these effects may be partly mediated by ROS generation and the activation of the mitochondrial programmed cell death pathway.
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http://dx.doi.org/10.3892/or.2018.6837DOI Listing
January 2019

Tip60 Suppresses Cholangiocarcinoma Proliferation and Metastasis via PI3k-AKT.

Cell Physiol Biochem 2018 11;50(2):612-628. Epub 2018 Oct 11.

Background/aims: Aberrant expression of Tip60 is associated with progression in many cancers. However, the role of Tip60 in cancer progression remains contradictory. The aim of this study was to investigate the clinical significance, biological functions and underlying mechanisms of Tip60 deregulation in cholangiocarcinoma (CCA) for the first time.

Methods: Quantitative real-time PCR (QRT-PCR), western blotting and immunohistochemistry staining (IHC) were carried out to measure Tip60 expression in CCA tissues and cell lines. Kaplan-Meier analysis and the log-rank test were used for survival analysis. In vitro, cell proliferation was evaluated by flow cytometry and CCK-8, colony formation, and EDU assays. Migration/ invasion was evaluated by trans-well assays. Phosphokinase array was used to confirm the dominant signal regulated by Tip60. Tumor growth and metastasis were demonstrated in vivo using a mouse model.

Results: Tip60 was notably downregulated in CCA tissues, which was associated with greater tumor size, venous invasion, and TNM stage. Down-regulation of Tip60 was associated with tumor progression and poorer survival in CCA patients. In vitro and in vivo studies demonstrated that Tip60 suppressed growth and metastasis throughout the progression of CCA. We further identified the PI3K/AKT pathway as a dominant signal of Tip60 and suggested that Tip60 regulated CCA cell proliferation and metastasis via PT3K-AKT pathway. Pearson analysis revealed that PTEN was positively correlated with the Tip60 level in CCA tissues.

Conclusion: Tip60, as a tumor suppressor in CCA via the PI3K/AKT pathway, might be a promising therapeutic target or prognostic marker for CCA.
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http://dx.doi.org/10.1159/000494183DOI Listing
November 2018

Effect of Colloidal Silica on the Hydration Behavior of Calcium Aluminate Cement.

Materials (Basel) 2018 Sep 28;11(10). Epub 2018 Sep 28.

The State Key Laboratory of Refractories and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, China.

The effect of colloidal silica (CS) on the hydrate phases and microstructure evolution of calcium aluminate cement (CAC) was investigated. Samples hydrated with CS were obtained and characterized by X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared spectroscopy (FT-IR), hydration heat measurement and Nuclear Magnetic Resonance (NMR). The results revealed that SiO₂ nanoparticles may affect the hydrates crystallization process. There was a compact structure in the CAC paste with CS, while petal-shaped hydrates with a porous structure were formed in the pure CAC paste. The maximum value of electrical conductivity for CAC paste with CS suggested that the early stage of hydration for CAC was accelerated. However, the hydration heat curves revealed that the late stage of the CAC hydration process was inhibited, and the hydration degree was reduced, this result was in accordance with Thermogravimetry-Differential scanning calorimetry(TG-DSC) curves. The fitting results of hydration heat curves further showed that the hydration degree at NG (nucleation and crystal growth) process stage was promoted, while it was limited at the phase boundaries stage, and the diffusion stage in the hydration reaction was brought forward due to the addition of CS. According to these results and analyses, the differences in the hydration process for CAC with and without CS can be attributed to the distribution and nucleation effect of SiO₂ nanoparticles.
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http://dx.doi.org/10.3390/ma11101849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213958PMC
September 2018

Immune Responsive Release of Tacrolimus to Overcome Organ Transplant Rejection.

Adv Mater 2018 Nov 25;30(45):e1805018. Epub 2018 Sep 25.

CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui, 230026, China.

Transplant rejection is the key problem in organ transplantation and, in clinic, immunosuppressive agents such as tacrolimus are directly administered to the recipients after surgery for T-cell inhibition. However, direct administration of tacrolimus may bring severe side effects to the recipients. Herein, by rational design of two hydrogelators NapPhePheGluTyrOH (1) and Nap d-Phe dPheGluTyrOH (2), a facile method of immune responsive release of tacrolimus is developed from their hydrogels to overcome organ transplantation rejection. Upon incubation with protein tyrosine kinase, which is activated in T cells after organ transplantation, the tacrolimus-encapsulating Gel 1 or Gel 2 is disassembled to release tacrolimus. Cell experiments show that both Gel 1 and Gel 2 have better inhibition effect on the activated T cells than free drug tacrolimus. Liver transplantation experiments indicate that, after 7 days of treatment of same dose tacrolimus, the recipient rats in the Gel 2 group show significantly extended median survival time of 22 days while the recipients treated with conventional tacrolimus medication have a median survival time of 13 days. It is expected herein that this "smart" facile method of immune responsive release of tacrolimus can be applied to overcome organ transplantation rejection in clinic in the near future.
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http://dx.doi.org/10.1002/adma.201805018DOI Listing
November 2018

Research Status and Prospect on Vanadium-Based Catalysts for NH₃-SCR Denitration.

Materials (Basel) 2018 Sep 6;11(9). Epub 2018 Sep 6.

The State Key Laboratory of Refractories and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, China.

Selective catalytic reduction of NO with NH₃ is one of the most widely used technologies in denitration. Vanadium-based catalysts have been extensively studied for the deNO process. V₂O₅/WO₃(MoO₃)TiO₂ as a commercial catalyst has excellent catalytic activity in the medium temperature range. However, it has usually faced several problems in practical industrial applications, including narrow windows of operation temperatures, and the deactivation of catalysts. The modification of vanadium-based catalysts will be the focus in future research. In this paper, the chemical composition of vanadium-based catalysts, catalytic mechanism, the broadening of the temperature range, and the improvement of erosion resistance are reviewed. Furthermore, the effects of four major systems of copper, iron, cerium and manganese on the modification of vanadium-based catalysts are introduced and analyzed. It is worth noting that the addition of modified elements as promoters has greatly improved the catalytic performance. They can enhance the surface acidity, which leads to the increasing adsorption capacity of NH₃. Surface defects and oxygen vacancies have also been increased, resulting in more active sites. Finally, the future development of vanadium-based catalysts for denitration is prospected. It is indicated that the main purpose for the research of vanadium-based modification will help to obtain safe, environmentally friendly, efficient, and economical catalysts.
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http://dx.doi.org/10.3390/ma11091632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164654PMC
September 2018

Metformin induces miR-378 to downregulate the CDK1, leading to suppression of cell proliferation in hepatocellular carcinoma.

Onco Targets Ther 2018 31;11:4451-4459. Epub 2018 Jul 31.

Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China,

Metformin is one of the extensively and most commonly used oral antihyperglycemic agents, but it has been shown to exert antineoplastic effects in many cancer cells. Recent studies have confirmed that metformin has an antitumor effect on hepatocellular carcinoma (HCC). However, the molecular mechanism underlying this effect needs to be further studied.

Materials And Methods: CDK1 and miR-378 expression was analyzed by western blotting and real-time PCR assays. We confirmed the association between miR-378 and CDK1 by dual luciferase reporter assay. The role of the miR-378/CDK1 pathway in proliferation, cell cycle and apoptosis was examined in vitro. The effect of miR-378 on HCC tumor growth was evaluated in nude xenograft mouse model.

Results: Our study found that metformin significantly inhibited the HCC cell proliferation via inducing G2/M arrest. At the same time, metformin efficiently decreased CDK1 expression and elevated miR-378 level. Moreover, the upregulation of miR-378 also repressed HCC cell proliferation by causing G2/M arrest and inhibited tumor growth. Additionally, we demonstrated that miR-378 directly targeted CDK1 3'UTR and downregulated CDK1 mRNA and protein levels. Furthermore, metformin treatment could not decrease CDK1 expression, suppress HCC cell proliferation, and induce G2/M cell cycle arrest.

Discussion: Metformin-suppressed HCC cell proliferation was dependent on the inhibitory effect of miR-378 on CDK1 expression. Taken together, we concluded that metformin inhibited HCC cell proliferation via modulating miR-378/CDK1 axis.

Conclusion: Collectively, the current results provide the first evidence, to our knowledge, that miR-378/CDK1 axis is involved in metformin modulating the proliferation of HCC cells, which suggests a novel molecular mechanism underlying the thera peutic effect of metformin on HCC.
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http://dx.doi.org/10.2147/OTT.S167614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074828PMC
July 2018

Catalytic Transformation of Lignocellulosic Biomass into Arenes, 5-Hydroxymethylfurfural, and Furfural.

ChemSusChem 2018 Aug 16;11(16):2758-2765. Epub 2018 Jul 16.

Shanghai Key Laboratory of Functional Materials Chemistry, Research Institute of Industrial Catalysis;, School of Chemistry and Molecular Engineering, East China University of Science and Technology, No. 130 Meilong Road, Shanghai, 200237, P. R. China.

The complete transformation of lignocellulosic biomass into valuable platform chemicals is of great significance. Herein, a catalytic process for the upgrading of lignocellulose to arenes, 5-hydroxymethylfurfural (HMF), and furfural is reported. Firstly, the lignin fraction in lignocellulosic biomass is selectively converted into lignin oil (82.9 mol % yield of lignin monomers from birch wood) over a Pd/C catalyst and then further hydrodeoxygenated to arenes in catalytic hydrogen-transfer reactions over a Ru/Nb O catalyst. High yields of C -C hydrocarbons (95.6 mol %) with 85.6 wt % selectivity to arenes based on lignin oil are achieved owing to the synergistic effect between Ru and Nb O , which enables direct hydrogenolysis of the C -OH bond in phenolics. Secondly, the cellulose and hemicellulose fractions in the Pd/C-containing solid residue, as well as methylated C sugars produced during the stripping of lignin, are converted into HMF and furfural with a total yield of up to 24.5 wt % (based on the amount of birch wood) in a THF/concentrated seawater (ca. 30 wt % salts) biphasic reaction system. Here, seawater played a key role in the conversion of cellulose and hemicellulose into HMF and furfural, respectively; more importantly, it made the separation and reuse of the Pd/C catalyst easier. With this catalytic process, the complete and efficient transformation of lignocellulose into highly value-added products with recycling of each catalyst and solvent has been realized.
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http://dx.doi.org/10.1002/cssc.201800967DOI Listing
August 2018

Association of five genetic variations in DNMT1 and DNMT3A with gastric cancer in a Chinese population.

Future Oncol 2018 Jul 29;14(17):1731-1739. Epub 2018 Jun 29.

Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.

Aim: To determine whether genetic variations in DNMT1 and DNMT3A could be associated with gastric cancer risk.

Materials & Methods: A total of 466 patients and 452 healthy controls were enrolled in this study. Genotypes were examined by using the Sequenom MassARRAY platform.

Results: No significant differences in the distribution frequencies were observed between the groups. However, subgroup analysis revealed that, in the group aged ≤60 years, DNMT3A rs13420827 was associated with reduced gastric cancer risk, and that carrier of GC/GG genotype was associated with reduced risk of gastric cancer with low differentiation or at the T3-T4 stage.

Conclusion: This study suggests that five genetic variations of interest in DNMT1 and DNMT3A are not associated with the presence of gastric cancer, but that rs13420827 may contribute to the gastric cancer risk for those younger individuals, the risk of which may be influenced by the characteristics of tumor.
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http://dx.doi.org/10.2217/fon-2017-0707DOI Listing
July 2018

Prognostic factors for operable biliary tract cancer: serum levels of lactate dehydrogenase, a strong association with survival.

Onco Targets Ther 2018 4;11:2533-2543. Epub 2018 May 4.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.

Background: Biliary tract cancers (BTCs) are uncommon but fatal, with a low 5-year survival rate after surgical resection. This study was designed to investigate the prognostic factors for operable BTC.

Methods: Baseline demographics at diagnosis were retrospectively evaluated in 341 BTC patients undergoing radical surgery at The First Affiliated Hospital of Nanjing Medical University from January 2011 to December 2015. The association between prognostic factors and overall survival (OS) was determined by multivariate analysis using the Cox proportional hazards regression model.

Results: Our study showed that 341 patients were included in the analysis, of which 166 (48.7%) were males and 175 (51.3%) were females. Older age, depth of tumor invasion, positive surgical margin, lower hemoglobin, and higher lactic dehydrogenase (LDH) were associated with significantly worse OS using multivariate analysis. In the entire cohort, the estimate of median OS in patients with LDH <271 U/L was 36.291 months (95% CI; 30.989-41.594 months), and 30.736 months (95% CI; 19.154-42.318 months) in patients with LDH ≥271 U/L (adjusted HR-1.505, 95% CI; 1.009-2.245, = 0.045). Moreover, it was investigated whether serum LDH retained its significance as a prognostic marker in BTC subgroups separately. The results showed that LDH was prognostic in patients with distal bile duct (DBD) carcinoma undergoing radical surgery (HR-2.452, 95% CI; 1.167-5.152, = 0.018). However, there were no statistical differences between LDH and OS in multivariate analysis in the other three individual subgroups except for DBD carcinoma. This may be due to the limited number of patients in the study, indicating that a greater number of patients may be required for statistical significance.

Conclusion: Older age, depth of tumor invasion, positive surgical margin status, lower hemoglobin levels, and elevated serum LDH level are associated with poor survival in operable BTC patients. Serum LDH level is a cost-effective prognostic biomarker in patients with operable BTC and especially DBD carcinoma.
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http://dx.doi.org/10.2147/OTT.S150502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942178PMC
May 2018