RETRACTED: Lai et al. MicroRNA-21 Plays Multiple Oncometabolic Roles in the Process of NAFLD-Related Hepatocellular Carcinoma via PI3K/AKT, TGF-ß, and STAT3 Signaling. Cancers 2021, 13, 940.

The Cancers Editorial Office retracts the article, "MicroRNA-21 Plays Multiple Oncometabolic Roles in the Process of NAFLD-Related Hepatocellular Carcinoma via PI3K/AKT, TGF-ß, and STAT3 Signaling" [...].

Integration of in-situ chemical oxidation and permeable reactive barrier for the removal of chlorophenols by copper oxide activated peroxydisulfate.

In-situ chemical oxidation (ISCO) and permeable reactive barrier (PRB) have been used in field practices for contaminated groundwater remediation. In this lab-scale study, a novel system integrating ISCO and PRB using peroxydisulfate (PDS) as the oxidant and copper oxide (CuO) as the reactive barrier material was developed for the removal of 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP) and pentachlorophenol (PCP). The influences of chlorophenol concentration and flow rate on the system performance were first evaluated using synthetic solutions. The removal efficiencies of target chlorophenols were greater than 90% when sufficient PDS was supplied ([PDS]/[chlorophenol]>1). It was also found that the removal efficiencies decreased with the increasing chlorophenol concentrations (10-150 µM) and flow rates (1.8-14.4 mL/min). When three real groundwaters were employed, the removal efficiencies of 2,4-DCP and 2,4,6-TCP slightly reduced to 90% and 85%, respectively. For PCP, the removal efficiency dropped to 20% in two groundwaters with relatively high levels of alkalinity. The influences of pH and TOC were found to be insignificant for the range investigated (pH 6.5-8.7 and TOC = 0.4-1.5 mgC/L). The reduced removal efficiency could be due to the formation of weaker radicals and the stronger competition between bicarbonate ions and PDS for the activation sites on the CuO surfaces.

Correction: Lai et al. MicroRNA-21 Plays Multiple Oncometabolic Roles in the Process of NAFLD-Related Hepatocellular Carcinoma via PI3K/AKT, TGF-ß, and STAT3 Signaling. Cancers 2021, 13, 940.

The authors wish to make the following corrections to this paper [...].

Quantitative Measurement of Breast Tumors Using Intravoxel Incoherent Motion (IVIM) MR Images.

Breast magnetic resonance imaging (MRI) is currently a widely used clinical examination tool. Recently, MR diffusion-related technologies, such as intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI), have been extensively studied by breast cancer researchers and gradually adopted in clinical practice. In this study, we explored automatic tumor detection by IVIM-DWI. We considered the acquired IVIM-DWI data as a hyperspectral image cube and used a well-known hyperspectral subpixel target detection technique: constrained energy minimization (CEM). Two extended CEM methods-kernel CEM (K-CEM) and iterative CEM (I-CEM)-were employed to detect breast tumors. The K-means and fuzzy C-means clustering algorithms were also evaluated. The quantitative measurement results were compared to dynamic contrast-enhanced T1-MR imaging as ground truth. All four methods were successful in detecting tumors for all the patients studied. The clustering methods were found to be faster, but the CEM methods demonstrated better performance according to both the Dice and Jaccard metrics. These unsupervised tumor detection methods have the advantage of potentially eliminating operator variability. The quantitative results can be measured by using ADC, signal attenuation slope, D*, D, and PF parameters to classify tumors of mass, non-mass, cyst, and fibroadenoma types.

MicroRNA-21 Plays Multiple Oncometabolic Roles in the Process of NAFLD-Related Hepatocellular Carcinoma via PI3K/AKT, TGF-ß, and STAT3 Signaling.

MicroRNA-21 (miR-21) is one of the most frequently upregulated miRNAs in liver diseases such as nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). However, mechanistic pathways that connect NAFLD and HCC remain elusive. We developed a doxycycline (Dox)-inducible transgenic zebrafish model (LmiR21) which exhibited an upregulation of miR-21 in the liver, which in turn induced the full spectrum of NAFLD, including steatosis, inflammation, fibrosis, and HCC, in the LmiR21 fish. Diethylnitrosamine (DEN) treatment led to accelerated liver tumor formation and exacerbated their aggressiveness. Moreover, prolonged miR-21 expression for up to ten months induced nonalcoholic steatohepatitis (NASH)-related HCC (NAHCC). Immunoblotting and immunostaining confirmed the presence of miR-21 regulatory proteins (i.e., PTEN, SMAD7, p-AKT, p-SMAD3, and p-STAT3) in human nonviral HCC tissues and LmiR21 models. Thus, we demonstrated that miR-21 can induce NAHCC via at least three mechanisms: First, the occurrence of hepatic steatosis increases with the decrease of ptenb, pparaa, and activation of the PI3K/AKT pathway; second, miR-21 induces hepatic inflammation (or NASH) through an increase in inflammatory gene expression via STAT3 signaling pathways, and induces liver fibrosis through hepatic stellate cell (HSC) activation and collagen deposition via TGF-ß/Smad3/Smad7 signaling pathways; finally, oncogenic activation of Smad3/Stat3 signaling pathways induces HCC. Our LmiR21 models showed similar molecular pathology to the human cancer samples in terms of initiation of lipid metabolism disorder, inflammation, fibrosis and activation of the PI3K/AKT, TGF-ß/SMADs and STAT3 (PTS) oncogenic signaling pathways. Our findings indicate that miR-21 plays critical roles in the mechanistic perspectives of NAHCC development via the PTS signaling networks.

MicroRNA-155 inhibits dengue virus replication by inducing heme oxygenase-1-mediated antiviral interferon responses.

MicroRNAs (miRNAs) have been reported to directly alter the virus life cycle and virus-host interactions, and so are considered promising molecules for controlling virus infection. In the present study, we observed that miR-155 time-dependently downregulated upon dengue virus (DENV) infection. In contrast, exogenous overexpression of miR-155 appeared to limit viral replication in vitro, suggesting that the low levels of miR-155 would be beneficial for DENV replication. In vivo, overexpression of miR-155 protected ICR suckling mice from the life-threatening effects of DENV infection and reduced virus propagation. Further investigation revealed that the anti-DENV activity of miR-155 was due to target Bach1, resulting in the induction of the heme oxygenase-1 (HO-1)-mediated inhibition of DENV NS2B/NS3 protease activity, ultimately leading to induction of antiviral interferon responses, including interferon-induced protein kinase R (PKR), 2'-5'-oligoadenylate synthetase 1 (OAS1), OAS2, and OAS3 expression, against DENV replication. Collectively, our results provide a promising new strategy to manage DENV infection by modulation of miR-155 expression.

ERK Activation Modulates Cancer Stemness and Motility of a Novel Mouse Oral Squamous Cell Carcinoma Cell Line.

We established the NHRI-HN1 cell line from a mouse tongue tumor induced by 4-nitroquinoline 1-oxide (4-NQO)/arecoline, with further selection for cell stemness via in vitro sphere culture, to evaluate potential immunotherapies for oral squamous cell carcinoma (OSCC) in East and Southeast Asia. In vivo and in vitro phenotypic characterization, including tumor growth, immune modulator administration, gene expression, morphology, migration, invasion, and sphere formation assays, were conducted. NHRI-HN1 cells are capable of generating orthotopic tumors in syngeneic mice. Interestingly, immune stimulation via CpG oligodeoxynucleotide (CpG-ODN) dramatically reduced the tumor growth in NHRI-HN1 cell-injected syngeneic mice. The pathways enriched in genes that were differentially expressed in NHRI-HN1 cells when compared to non-tumorigenic cells were similar to those that were identified when comparing human OSCC and non-tumorous tissues. NHRI-HN1 cells have characteristics of epithelial-mesenchymal transition (EMT), including enhanced migration and invasion. NHRI-HN1 cells showed aggressive cell growth and sphere formation. The blockage of extracellular signal-regulated kinase (ERK) activation suppressed cell migration and reduced stemness characteristics in NHRI-HN1 cells, similar to human OSCC cell lines. Our data suggest that NHRI-HN1 cells, showing tumorigenic characteristics of EMT, cancer stemness, and ERK activation, are sufficient in modeling human OSCC and also competent for use in investigating oral cancer immunotherapies.

FUT2 genetic variants as predictors of tumor development with hepatocellular carcinoma.

Lewis antigens related to the ABO blood group are fucosylated oligosaccharides and are synthesized by specific glycosyltransferases (FUTs). FUTs are involved in various biological processes including cell adhesion and tumor progression. The fucosyltransferase-2 gene (FUT2) encodes alpha (1,2) fucosyltransferase, which is responsible for the addition of the alpha (1,2)-linkage of fucose to glycans. Aberrant fucosylation occurs frequently during the development and progression of hepatocellular carcinoma (HCC). However, the association of FUT2 polymorphisms with HCC development has not been studied. Therefore, we aimed to investigate the association of FUT2 polymorphisms with demographic, etiological, and clinical characteristics and with susceptibility to HCC. In this study, a total of 339 patients and 720 controls were recruited. The genotypes of FUT2 at four single-nucleotide polymorphisms (SNPs; rs281377, rs1047781, rs601338, and rs602662) were detected by real-time polymerase chain reaction from these samples. Compared with the wild-type genotype at SNP rs1047781, which is homozygous for nucleotides AA, at least one polymorphic T allele (AT or TT) displayed significant association with clinical stage (p = 0.048) and tumor size (p = 0.022). Our study strongly implicates the polymorphic locus rs1047781 of FUT2 as being associated with HCC development.

Phytochemicals and Estrogen-Receptor Agonists from the Aerial Parts of Liriope platyphylla.

One new benzofuran, (2R)-(2',4'-dihydroxybenzyl)-6,7-methylenedioxy-2,3-dihydrobenzofuran (1), one new phenylisocoumarin, 3-(2'-hydroxyphenyl)-6,8-dihydroxy-7-methoxy-isocoumarin (2), and one new benzofuroisocoumarin, platyphyllarin C (3), were isolated from the ethanolic extract of Liriope platyphylla aerial parts, along with seventeen known compounds. The structures of the isolates were established by spectroscopic analysis and comparison with the literature data. The results indicated that structures 1-3 are uncommon in Nature. Benzofuroisocoumarin 4, flavonoids 9, 10, and 13-15, and homoisoflavonoids 19 and 20 exhibited significant binding activity to estrogen-receptor α and/or ß as demonstrated by the SEAP reporter assay system in an MCF-7 cell-line.

Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound healing in a murine model of a full-thickness defect.

INTRODUCTION: The promotion of wound healing using dermal substitutes has become increasingly widespread, but the outcomes of substitute-assisted healing remain functionally deficient. Adipose-derived stem cells (ASCs) have been investigated widely in regenerative medicine and tissue engineering, and they have the potential to enhance wound healing. In this study, we focused on investigating the effects and mechanism of ASCs combined with an acellular dermal matrix (ADM) to treat full-thickness cutaneous wounds in a murine model. METHODS: The ADM was prepared from the dorsal skin of nude mice by decellularization by treatment with trypsin followed by Triton X-100. The human ASCs were isolated and cultured from abdominal lipoaspirate. We created a rounded, 8-mm, full-thickness cutaneous wound in nude mice and divided the mice into the following 4 groups: silicon sheet cover only, silicon sheet with spreading ASCs, ADM only, and ASCs seeded on ADM. The granulation thickness was evaluated by histology after 7 days. Further comparisons between the ADM only and ASC-seeded ADM groups were undertaken by assessing the reepithelialization ratio and blood vessel density at postoperative days 9 and 14. Statistical analyses were conducted using Student 2-tailed t test. Immunofluorescent histology and ASC labeling were also performed to identify possible mechanisms. RESULTS: The ADM was successfully prepared, and the cytometry analysis and differentiation assay provided the characterization of the human ASCs. A marked improvement in granulation thickness was detected in the ADM-ASC group in comparison with other 3 groups. A significantly increased rate of reepithelialization in the ADM-ASC group (80 ± 6%) compared to the ADM only group (60 ± 7%) was noted on postoperative day 9. The blood vessel density was evidently increased in the ADM-ASC group (7.79 ± 0.40 vessels per field) compared to the ADM only group (5.66 ± 0.23 vessels) on day 14. Cell tracking experiments demonstrated that labeled ASCs were colocalized with staining for VEGF or endothelial cell maker vWF after the transplantation of ADM-ASCs on postoperative day 14. CONCLUSIONS: Adipose-derived stem cells seeded on an ADM can enhance wound healing, promote angiogenesis, and contribute to newly formed vasculature, and VEGF-expressing ASCs can be detected after transplantation. This model could be used to improve the other clinical applications of ASCs and to decipher the detailed mechanism by which ASCs interact with wound tissue.

Physalin B from Physalis angulata triggers the NOXA-related apoptosis pathway of human melanoma A375 cells.

Melanoma is a lethal form of skin cancer that can metastasize rapidly. While surgery and radiation therapy provide palliative therapy for local tumor growth, systemic therapy is the mainstay of treatment for metastatic melanoma. However, limited chemotherapeutic agents are available for melanoma treatment. In this study, we investigated the anti-melanoma effect of physalin B, the major active compound from a widely used herb medicine, Physalis angulata L. This study demonstrated that physalin B exhibits cytotoxicity towards v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutated melanoma A375 and A2058 cells (the IC50 values are lower than 4.6 µg/ml). Cytotoxicity is likely resulted from apoptosis since the apoptotic marker phosphatidylserine are detected immediately under physalin B treatment and apoptotic cells formation. Further examination revealed that physalin B induces expression of the proapoptotic protein NOXA within 2 h and later triggers the expression of Bax and caspase-3 in A375 cells. These results indicate that physalin B can induce apoptosis of melanoma cancer cells via the NOXA, caspase-3, and mitochondria-mediated pathways, but not of human skin fibroblast cells and myoblastic cells. Thus, physalin B has the potential to be developed as an effective chemotherapeutic lead compound for the treatment of malignant melanoma.

Overexpression of gankyrin induces liver steatosis in zebrafish (Danio rerio).

Gankyrin is a small ankyrin-repeat protein that previous research has confirmed to be overexpressed in hepatocellular carcinoma (HCC). Although relevant literature has reported on gankyrin functions in cellular proliferation and tumorigenesis, the exact role of gankyrin is poorly understood in animal model systems. This study analyzed hepatic lipid accumulation in gankyrin transgenic (GK) zebrafish. Bromodeoxyuridine (BrdU)-positive cells were predominantly increased in the liver bud of GK larvae, indicating that gankyrin functionally promoted cell proliferation at the larval stage in GK fish. However, over 90% of the viable GK adults showed an increased lipid content, leading in turn to liver steatosis. Liver histology and oil red O staining also indicated the accumulation of fatty droplets in GK fish, consistent with the specific pathological features of severe steatosis. Molecular analysis revealed that gankyrin overexpression induced hepatic steatosis and modulated the expression profiles of four hepatic microRNAs, miR-16, miR-27b, miR-122, and miR-126, and 22 genes involved in lipid metabolism. Moreover, significantly increased hepatic cell apoptosis resulted in liver damage in GK adults, leading to liver failure and death after approximately 10months. This study is the first to report gankyrin as a potential link between microRNAs and liver steatosis in zebrafish.

Do aggressive imaging features correlate with advanced histopathological grade in meningiomas?

Atypical and malignant meningiomas are more likely to recur than benign meningiomas. We aimed to distinguish atypical and malignant meningiomas from benign meningiomas based on imaging findings. Between 2004 and 2007, a total of 75 patients with resected intracranial meningiomas were retrospectively reviewed. Histopathological grades were assigned as benign and atypical/malignant meningiomas according to the World Health Organization (WHO) classification. All patients received preoperative CT scans and MRI studies. Six aggressive imaging features were evaluated and compared between the two groups: (i) intratumoral cystic change; (ii) hyperostosis of the adjacent skull; (iii) bony destruction; (iv) extracranial tumor extension through the skull base foramina; (v) arterial encasement; and (vi) peritumoral brain edema. There were 59 benign and 16 atypical/malignant meningiomas. Only intratumoral cystic change and extracranial tumor extension through the skull base foramina were more prevalent in atypical/malignant meningiomas (p=0.001). Hence, these two imaging features might be potential markers of atypical/malignant meningiomas.

Liver-specific expression of p53-negative regulator mdm2 leads to growth retardation and fragile liver in zebrafish.

Tumorigenesis requires inactivation of the p53 tumor suppressor pathway, likely involving the negative regulator Mdm2 protein. To analyze the possible roles of Mdm2 in oncogenesis and other functions during zebrafish hepatogenesis, we generated transgenic zebrafish by liver-specific Mdm2 over-expression utilizing a fusion between genes encoding GFP and mdm2, GFP::Mdm2. Over-expression of GFP::Mdm2 in the zebrafish liver did not interrupt normal liver development in the larval stages but approximately 30% of the adult fish raised from the same larvae displayed obvious growth retardation at 16 weeks of age. Most growth-retarded adults displayed liver atrophy, contraction, or hypoplasia, which proved lethal within 4 to 8 months. Histologically, over-expression of GFP::Mdm2 in Gmdm2-liver leading to liver degeneration may in some way have been due to an increased cell apoptosis accompanied by a slightly interrupted cell cycle or hepatocyte proliferation. Liver degeneration or other transgenic phenotypes were not associated with liver cancer; however, liver-degenerated phenotypes could be passed to wild-type zebrafish. In this study, we generated transgenic zebrafish lines with a "fragile liver." The "fragile liver" zebrafish can provide a model for molecular pathology of liver diseases and for screening small molecules that affect mdm2-related pathways.

Clinical entity and treatment strategies for adult intussusceptions: 20 years' experience.

PURPOSE: Intestinal intussusception in adults is rare and the optimal management of this problem remains controversial. The purpose of this study was to determine the causes of intussusceptions in adults and to assess their treatment. METHODS: A retrospective review of patients older than aged 18 years who were diagnosed with intestinal intussusception at Tri-Service General Hospital between July 1984 and July 2004 was conducted. RESULTS: During the 20-year period, there were 292 patients with intussusception, 24 (8.2 percent) of which were adults. Abdominal pain was the most common presenting complaint (79.2 percent). The diagnosis of adult intussusception was made preoperatively in 18 cases (75 percent) and intraoperatively in 6 cases (25 percent). Of the 24 patients, 20 (83.3 percent) had a defined lesion; 11 (55 percent) lesions were benign and 9 (45 percent) were malignant. In eight patients (33.3 percent), the intussusception was reduced; perforation occurred in one patient (12.5 percent). Segmental resections were performed on 14 patients (58.3 percent), right hemicolectomies on 6 patients (25 percent), laparoscopic low anterior resection on 1 patient (4.2 percent), appendectomy on 1 patient (4.2 percent), and diverticulectomy on 1 patient (4.2 percent). Intraoperative colonoscopy was performed on three patients (12.5 percent) before reduction (lipomas were noted in 2 of the patients (66.7 percent) with limited resection of the ileum and preservation of the antireflux ileocecal valve. There was one perioperative mortality (4.2 percent) and seven postoperative morbidities (29.2 percent). CONCLUSIONS: Adult intussusception is an unusual and challenging condition and is a preoperative diagnostic problem. We discuss our 20 years of experience in treatment strategies for dealing with such unusual problems.

Hepatocutaneous fistula: a complication after radiofrequency ablation therapy for hepatocellular carcinoma.

A 34-year-old male was admitted for recurrent hepatocellular carcinoma (HCC) with poor healing of a radiofrequency ablation wound over the subxiphoid region. The patient underwent lobectomy of the liver 3 years previously. Transarterial chemoembolisation was performed twice for tumour recurrence, and radiofrequency ablation was done for new recurrence 2 months previously. Due to poor healing with discharge through the puncture wound and elevated alpha feto-protein (AFP) level, recurrent hepatocellular carcinoma and tumour seeding of the needle tract were suspected. During surgery, a recurrent tumour mass over segment 3 with a hepatocutaneous fistula within the adhesion tissue between the liver surface and abdominal wall was discovered. We recommend that hepatocutaneous fistula should be considered as a complication of radiofrequency ablation for hepatic tumours.

Gossypiboma of the leg: MR imaging characteristics. A case report.

We report a 22-year-old man with a solid mass in the right proximal leg, which was furned out to be a gossypiboma. MR imaging revealed a well-defined mass lesion that showed intermediate signal intensity at T1-weighted imaging (T1WI) and slightly high signal intensity at T2-weighted imaging (T2WI). Wavy, low-signal-intensity stripes were visible within the fluid-filled central cavity. At surgical exploration, a sponge, retained after previous knee surgery, was discovered, and it was found that a granuloma had developed. Pathologic examination revealed granulomatous inflammation, with lymphocyte and giant cell infiltration. The presence of wavy, low-signal-intensity gauze fibers at T2WI may be a characteristic MR appearance of gossypiboma.