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Hepatocellular carcinoma (HCC) shows recurrence and lung metastasis even after treatment. 23-hydroxybetulinic acid (23-HBA), a major active constituent of Pulsatilla chinensis, exhibits potent antitumor activities. We herein investigate the biological effect of 23-HBA on metastasis and immunosuppression in a mouse model of HCC. Microarray-based gene expression profiling was employed to identify the target genes of 23-HBA in the treatment of HCC. The effect of 23-HBA on the progression of HCC was evaluated by in-vitro cell function measurements along with in-vivo xenograft implantation, lung metastasis and CD11b+Gr1+ staining experiments. The potential mechanism involving target signaling pathway was investigated by western blot analysis. Bioinformatics analysis revealed that matrix metalloproteinase 2 (MMP2) was a key target gene mediated by 23-HBA in HCC, whereas Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis demonstrated that MMP2 mainly affects the development and metastasis of HCC. 23-HBA significantly reduced cell malignant functions in vitro while delaying the HCC growth and metastasis in vivo. In addition, the number of myeloid-derived suppressor cells was shown to be reduced following administration of 23-HBA in mice. Mechanistic analysis indicated that these effects of 23-HBA during HCC were involved with the mitogen-activated protein kinase (MAPK) signaling pathway inactivation and resulted in decreased phosphorylation of both mitogen-activated protein kinases 1/2 and extracellular signal-regulated kinase 1/2. Our study reveals that 23-HBA acts as a tumor suppressor agent and suppresses HCC tumorigenesis, metastasis and immunosuppression via blockade of the MAPK signaling pathway, suggesting that 23-HBA may serve as a promising drug target to treat HCC.

Background The most effective treatment for advanced cirrhosis and portal hypertension is liver transplantation (LT). However, splenomegaly and hypersplenism can persist even after LT in patients with massive splenomegaly. Aim To examine the feasibility of performing partial splenectomy during LT in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism. Methods Between October 2015 and February 2019, 762 orthotopic LTs were performed for patients with end-stage liver diseases in Tianjin First Center Hospital. Eighty-four cases had advanced cirrhosis combined with severe splenomegaly and hypersplenism. Among these patients, 41 received partial splenectomy during LT (PSLT group), and 43 received only LT (LT group). Patient characteristics, intraoperative parameters, and postoperative outcomes were retrospectively analyzed and compared between the two groups. Results The incidence of postoperative hypersplenism (2/41, 4.8%) and recurrent ascites (1/41, 2.4%) in the PSLT group was significantly lower than that in the LT group (22/43, 51.2%; 8/43, 18.6%, respectively). Seventeen patients (17/43, 39.5%) in the LT group required two-stage splenic embolization, and further splenectomy was required in 6 of them. The operation time and intraoperative blood loss in the PSLT group (8.6 ± 1.3 h; 640.8 ± 347.3 mL) were relatively increased compared with the LT group (6.8 ± 0.9 h; 349.4 ± 116.1 mL). The incidence of postoperative bleeding, pulmonary infection, thrombosis and splenic arterial steal syndrome in the PSLT group was not different to that in the LT group, respectively. Conclusion Simultaneous PSLT is an effective treatment and should be performed in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism to prevent postoperative persistent hypersplenism.

B-doped core-shell Fe@BC nanozyme was synthesized. The peroxidase (POD) like activity of Fe@BC nanozyme was studied and utilized for detecting the activity of alanine aminotransferase (ALT). In the presence of ALT as well as ALT co-substrates L-alanine and α-ketoglutarate, L-glutamate is generated. The following catalytic oxidation of L-glutamate by glutamate oxidase leads to the generation of H

Jisan Sun, Wentao Jiang, Dazhi Tian, Qingjun Guo, Zhongyang Shen Department of Liver Transplantation, Tianjin First Center Hospital, First Clinical Institute of Tianjin Medical University, Nan Kai District, Tianjin 300192, People’s Republic of China Purpose: Hepatocellular carcinoma (HCC) accounts for one of the most prevalent tumor types in the world and still lacks an effective treatment regimen. The EGFR tyrosine-kinase inhibitor icotinib is capable of inhibiting proliferation of several kinds of cancer cells, but its anticancer effect in HCC is still not verified.Methods: In the current study, ten HCC cell lines were selected to test their original EGFR-activation status and PDL1 protein level, and in vitro antiproliferation assays were also conducted to analyze the IC50 and further investigate the correlation between IC50 and protein level of phosphorylated EGFR and PDL1. A in vivo nude mouse xenograft animal model was used as well to analyze its anticancer effect.Results: Icotinib showed significant inhibitory effects only on HCC cell lines that had both higher p-EGFR and PDL1 protein level. This specific HCC cell line was subcutaneously injected to establish the in vivo xenograft tumor model, and icotinib reduced tumor weight remarkably and growth dose dependently. Molecular mechanism study revealed that icotinib inhibited the phosphorylation of EGFR and PDL1 expression in cancer cells and activated apoptosis. Knocking down PDL1 significantly reduced the inhibitory effect of icotinib on HCC, and knocking in PDL1 increased the sensitivity of icotinib in HCC.Conclusion: The current research suggests that icotinib has an inhibitory effect on a subgroup of HCC cells that have both higher p-EGFR and PDL1. This hints at the potential clinical usage of icotinib in HCC based on PDL1-biomarker examination. Keywords: hepatocellular carcinoma, epidermal growth factor receptor, icotinib, PDL1 protein

Fluorescent hydroxyapatite nanoparticles (HAP-NPs) were synthesized by introducing trisodium citrate during the HAP-NP synthesis process. The HAP-NPs display strong emission at around 440 nm when excited at 340 nm. In the presence of low levels of biothiols, such as cysteine (Cys) and homocysteine (hCys), the fluorescence intensity of HAP-NPs was found to be enhanced, while for the same concentration of glutathione (GSH), a smaller fluorescence intensity increase was observed. So a selective and sensitive fluorescence turn-on assay for detection of low levels of biothiols is reported. The linear range of the assay for Cys is from 2 to 100 nM, and for hCys is from 2 to 200 nM. The assay was successfully applied to the detection of Cys in human serum samples. The interesting fluorescence properties of HAP-NPs, plus their good biocompatibility, mean that HAP-NPs may find wide application as fluorescence probes in different assays and bio-imaging areas.

The authors describe a dual signal amplification strategy for improving the sensitivity of electrochemical aptasensor. Hydroxyapatite nanoparticles (HAP-NPs) serve as the support for deposition of the respective aptamer. Both the HAP-NPs and the aptamer contain phosphate groups which can react with molybdate to form a redox-active molybdophosphate precipitate on the surface of a glassy carbon electrode (GCE). On applying a relatively low voltage of 0.21 V (vs. Ag/AgCl), a current is generated whose intensity depends on the concentration of the analyte. The cancer biomarker platelet-derived growth factor BB (PDGF-BB) is chosen as a model antigen (analyte). The assay works by sequential deposition of antibody against PDGF-BB, analyte (PDGF-BB) and anti-PDGF-BB aptamer modified HAP-NPs on the GCE to form a sandwich structure. The amperometric signal is linear in the 0.1 pg.mL−1 to 10 ng.mL−1 PDGF-BB concentration range, with a detection limit as low as 50 fg.mL−1. The assay was successfully applied to the determination of PDGF-BB in serum samples. In our perception, this signal amplification strategy has a wide scope in that it can be adapted to the preparation of other aptasensors for biomarkers and related species.

We read with interest the leading article by Gerbes et al 1 published in Gut. This roundtable meeting article proposed that hepatocellular carcinoma (HCC) staging linked to first-line treatment indication can help clinicians guide patients through treatment decision-making process, patients and researchers need reliable ways to stage disease and predict prognosis. Controversies always exist during multidisciplinary team (MDT) decision-making for HCC patients within the Milan criteria (MC) due to the lack of evidence-based studies of composite multiparametric evaluations among the three potential curative therapies: liver transplantation (LT), liver resection (LR) and local ablation (LA).2–4 Herein, we retrospectively evaluated the efficacy of LT, LR and LA for HCC patients within the MC and explored an individualised assessment prediction model to assist with MDT decision-making. Institutional ethics committees approved the retrospective analyses of consecutive HCC patients admitted to two medical centres of Nankai University (Tianjin, China) between November 2011 and March 2016. A total of 283 HCC patients within the MC were finally enrolled and classified into LT (n=100), LR (n=89) and LA (n=94) groups based on the first-line treatments. Under the three treatment groups, subgroups were divided according to …

The bioavailability of lipids from an emulsion can be controlled and regulated by the property of the stabilizing interfacial layer. Here we evaluate how low-molecular weight surfactants including hexadecyl trimethyl ammonium bromide (CTAB), sodium dodecyl sulfate (SDS), and Tween 80 (T80) influence the interfacial behavior of lipase and bile extract on the surface of lipid droplets stabilized with gum arabic (GA). The lipolysis behavior was influenced by surfactant type and concentration. The results showed that anionic SDS could completely displace GA from droplet surface. Cationic CTAB might either adsorb onto existing GA layers or displace GA, whereas non-ionic T80 could co-adsorb with GA on the interface. When the concentration of surfactants was much higher than the critical micelle concentration (CMC), all the surfactants would form a dense adsorption layer on the droplet interface to prevent lipase from the direct contact with lipids. A considerable amount of surfactant in the aqueous phase may also compete with the bile salt and lipase, thus leading to suppressed digestion of lipids. Ionic surfactants would denature the lipase resulting in reduced enzyme activity, and T80 micelles may interact with the lipase, hindering their adsorption onto the droplet interface as well. These results were confirmed both by the digestion model and interfacial techniques. The results provided guidance for the development of emulsion-based delivery systems for functional lipid foods.

Oil-in-water (O/W) emulsions have been used as a delivery system to protect conjugated linoleic acid (CLA), a polyunsaturated fatty acid, from oxidation. Conventional gum arabic (GA) and two matured gum arabic samples (EM2 and EM10) were used as emulsifiers to prepare CLA-in-water emulsions. The emulsions have optimal physical and chemical stability at gum concentrations of 5% for all three gums. Emulsions with higher gum concentrations are more susceptible to lipid oxidation. This is attributed to reduced physical stability at higher gum concentrations because of the coalescence and depletion-induced flocculation of the emulsion droplets. The prooxidants iron and copper intrinsically contained in the gums could also contribute to this instability. Among the three gums, EM10 provides the most effective protection for CLA both physically and chemically, because of its superior interfacial properties over GA and EM2.