The nuclear receptor farnesoid X receptor (FXR) acts as a liver protector by regulating normal liver homeostasis. Spontaneously developed liver tumors have been found in FXR-null mice. However, the role of FXR in the tumorigenesis of human hepatocellular carcinoma (HCC) is still poorly understood. In this study, we measured the expression of FXR and its primary target gene, small heterodimer partner, and analyzed the clinical significance of FXR expression in HCC patients. A lentiviral vector that selectively overexpresses FXR was used to investigate the function of FXR in HCC cell proliferation both in vitro and in vivo. Our data showed that in human HCC, FXR expression was significantly reduced and was positively correlated with multiple malignant clinicopathological characteristics. Lentivirus-mediated exogenous FXR expression resulted in a marked increase of small heterodimer partner expression, significant repression of liver cancer cell proliferation, and tumor growth in nude mice. These results suggest that FXR may be of clinical and pharmacological importance as a promising biomarker of HCC. farnesoid X receptor; small heterodimer partner; tumor suppressor; proliferation HUMAN HEPATOCELLULAR CARCINOMA (HCC) is one of the most common human malignancies in the world and is prevalent in developing countries. In China, HCC has become the second highest cancer-related cause of death since the 1990s and accounts for 53% of all liver cancer deaths worldwide (12). The high mortality of HCC is due in large part to the lack of good biomarkers for early diagnosis and treatment assessment. Patients are often diagnosed at advanced stages, when most available therapies have only limited efficacy.The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and is highly expressed in the liver. FXR controls the expression of various genes involved in bile acid, lipid, and glucose metabolism (21). In recent years, the understanding of the role of FXR in the liver has developed from that as a metabolic regulator to the novel function as a cell protector implicated in liver regeneration (9, 23) and hepatocarcinogenesis (22). In 2007, we first reported that in the absence of FXR, mice displayed spontaneous development of liver tumors (22). In parallel, Kim et al. (10) published very similar observations showing that aged FXR-null mice had a high incidence of liver tumors. However, limited information was available regarding the role of FXR in the development and progression of human HCC.The nuclear receptor small heterodimer partner (SHP) is an important modulator of metabolic signaling pathways (1,8,20) and is a primary FXR target gene. One of the well-characterized mechanisms by which FXR regulates gene expression in the liver is through the induction of SHP. Recent studies (24, 25) have revealed the role of SHP in the inhibition of cellular proliferation. However, combined loss of FXR and SHP expression in human HCC has not been previously reported.In this study...

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The aza-semi-crown pentadentate ligand rigidified by pyridine and piperidine rings was designed and synthesized. It can react with Mn(II) in water to form complex with improved longitudinal relaxivity, leading to efficient signal intensity enhancement of vascular vessels under a clinical magnetic resonance imaging scanner.

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Anti-tumor therapy during the follow-up period, without a history of anti-tumor therapy prior to HCC rupture, small tumor length and number, and early BCLC stage are the most crucial predictors associated with satisfactory overall survival. Other factors play only a small role in overall survival.

In this work, highly porous MIL-101 materials using hydrochloric acid (HCl) or hydrofluoric acid (HF) as a mineralizer were synthesized.

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4–11.0) versus 8.0 months (95% CI, 6.6–9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1–27.3] vs. 15.7 months [13.0–20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

In this paper, metal-organic framework NH 2 -MIL-101(Cr) was prepared and used as an adsorbent for removing tetracycline from aqueous system. The results showed that NH 2 -MIL-101(Cr) had the better adsorption property for tetracycline. The adsorption capacities for tetracycline reached 36.15 and 48.80 % in 10 and 240 min, respectively. Additionally, the study of adsorption kinetics and thermodynamic theories showed that the adsorption kinetics and thermodynamic datum of tetracycline were adapted to the pseudo-second-order model and the Freundlich model, respectively. In the meantime, the adsorption process was considered as an endothermic process, spontaneous nature of the adsorption and chemical adsorption in dominating station.