miR-4461 Inhibits Liver Cancer Stem Cells Expansion and Chemoresistance via Regulating SIRT1.

MicroRNAs (miRNAs) were involved in tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, few miRNAs have been identified and entered clinical practice. We show here that miR-4461 expression is reduced in liver cancer stem cells (CSCs) and predicts the poor prognosis of HCC patients. Knockdown of miR-4461 enhances the self-renewal and tumorigenicity of liver CSCs. Conversely, forced miR-4461 expression inhibits liver CSCs self-renewal and tumorigenesis. Mechanically, miR-4461 directly targets sirtuin 1 (SIRT1) via binding to its 3'-UTR in liver CSCs. The correlation of miR-4461 and SIRT1 was confirmed in human HCC patients' tissues. Additionally, we found that miR-4461 overexpression hepatoma cells are more sensitive to cisplatin treatment. PDXs also showed that miR-4461 high HCC xenografts are sensitive to cisplatin treatment. Clinical cohort analysis further confirmed that HCC patients with high miR-4461 are benefited more from transcatheter arterial chemoembolization (TACE) treatment. In conclusion, our findings revealed the crucial role of the miR-4461 in liver CSCs expansion and cisplatin response, rendering miR-4461 as an optimal target for the prevention and intervention of HCC.

Ectopic bronchogenic cyst of liver misdiagnosed as gallbladder diverticulum: A case report.

BACKGROUND: Ectopic bronchogenic cysts are a type of congenital cystic tumor that are extremely difficult to diagnose and can be ectopically located in various organs, with the possibility of malignant transformation. Here we report a case of an ectopic bronchogenic cyst in the liver initially misdiagnosed as a gallbladder diverticulum. CASE SUMMARY: The patient was a middle-aged woman whose chief complaint was intermittent pain in the upper abdomen. Imaging examination revealed a cystic space in the left inner lobe of the liver. She was admitted to our hospital for treatment. Based on abdominal examination and imaging findings, the initial diagnosis was gallbladder diverticulum with cholestasis combined with chronic cholecystitis. However, following intraoperative observations and postoperative pathologic assessment, the diagnosis was revised to ectopic bronchogenic cyst of the liver. CONCLUSION: Radiologists, hepatobiliary and pancreatic surgeons, gastrointestinal surgeons, urologists, and even neurosurgeons should be aware and consider a possible diagnosis of ectopic bronchogenic cysts, especially when other types of cyst, cystadenoma, and other diseases are excluded. The disease and its complications should be detected and correctly diagnosed and treated as early as possible in order to avoid adverse outcomes.

A Novel Indolizine Derivative Induces Apoptosis Through the Mitochondria p53 Pathway in HepG2 Cells.

Indolizine derivatives are a class of compounds with excellent biological activity. In this study, a series of indolizine derivatives, compound 1 (C1), compound 2 (C2), compound 3 (C3), and compound 4 (C4), were synthesized. 3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide (MTT) assay was used to evaluate their cytotoxicity against HepG2 (p53-wild), A549, and HeLa cell lines. HepG2 cells apoptosis induced by C3 was determined using Hoechst staining and acridine orange/ethidium bromide staining. Cells' apoptotic ratio was measured by Annexin V-FITC/PI double staining. Changes in mitochondrial membrane potential and intracellular reactive oxygen species (ROS) in HepG2 cells after C3 treatment were determined. Immunofluorescence staining and Western blot analysis were carried out to detect p53 levels and analyze the apoptosis-associated proteins, respectively. Moreover, the cytotoxic activity of C3 was examined in two other hepatocellular carcinoma (HCC) cell lines with different p53 status including Huh-7 cells (p53-mutant) and Hep3B cells (p53-null). The results indicated that C3 showed stronger inhibition towards HepG2 cells than other cell lines. Fluorescent staining and flow cytometry analysis confirmed that C3 induced apoptosis of HepG2 cells. C3 could also increase intracellular ROS and cause a decrease in the mitochondrial membrane potential. C3 promoted p53 activation and increased p53 accumulation in nuclei. The expression of p53 and Bax was increased with the down-regulation of Bcl-2, which promoted the release of cytochrome c and caspase-3 activation. Collectively, the study demonstrated that C3 caused HepG2 cell apoptosis via the mitochondria p53 pathway. These results inspired us to further develop indolizine derivatives as potential potent inhibitors against liver cancer.

One-Pot Regiospecific Synthesis of Indolizines: A Solvent-Free, Metal-Free, Three-Component Reaction of 2-(Pyridin-2-yl)acetates, Ynals, and Alcohols or Thiols.

A novel approach for the synthesis of indolizines from 2-(pyridin-2-yl)acetates, ynals, and alcohols or thiols has been developed. This MCR (multicomponent reaction) that proceeds under the solvent- and metal-free conditions has provided a straightforward path to construct indolizines. Furthermore, this reaction demonstrates other attractive features such as widely available starting materials, mild conditions, good functional group tolerance, and high efficiency.