Application of noninvasive test (acoustic attenuation imaging and ultrasonic shear wave elastography) to grade nonalcoholic fatty liver disease: An observational study.

The aim of this study was to validate the diagnostic efficacy of acoustic attenuation imaging (ATI) and ultrasonic shear wave elastography (SWE) in classifying nonalcoholic fatty liver disease (NAFLD). A total of 100 patients with NAFLD were recruited from our hospital between January 2021 and December 2022. Patient demographics and clinical data were collected, and 2-dimensional ultrasound was used to screen patients based on liver echo characteristics. Patients without liver space-occupying lesions underwent routine ultrasound examinations. Imaging or serology was used to confirm the presence of fatty liver in patients or healthy individuals. Patients with alcoholic liver disease (alcohol equivalent content < 20 g/day for women, <30 g/day for men), as well as those with lenticular degeneration, total parenteral nutrition, autoimmune liver disease, drug-induced hepatitis, and viral hepatitis, were excluded from the study. Out of the 100 included patients, 24 had normal liver, 21 had mild fatty liver, 30 had moderate fatty liver, and 25 had severe fatty liver. There were age differences between the normal group and patients with mild fatty liver, and the average body mass index (BMI) varied across the 4 groups. As the severity of the disease increased, the average BMI also increased (P < .05). The ATI scores and SWE scores differed significantly among the different groups (P < .05), with both scores showing an upward trend as the fatty liver condition worsened. Correlation analysis revealed positive correlations between ATI and SWE scores and the degree of fatty liver (P < .05), positive correlations with BMI (P < .05), and negative correlations with high-density lipoprotein cholesterol expression (P < .05). The area under the curve (AUC) for the ATI score in diagnosing different degrees of fatty liver was > 0.750, and the AUC for the SWE score was also > 0.750. The AUC for SWE score in diagnosing different degrees of fatty liver ranged from 1.01 to 4.57, while the combined AUC for ATI and SWE scores was > 0.850, with respective cutoff values of 3.62, 5.72, and 7.57 based on the maximum approximate entry index. The combination of ATI and SWE has a significant impact on the grading diagnosis of NAFLD, and its application can be extended to clinical practice.

Protective effects of upregulated HO-1 gene against the apoptosis of human retinal pigment epithelial cells in vitro.

AIM: To investigate the protective effect of heme oxygenase-1 (HO-1) against H2O2-induced apoptosis in human ARPE-19 cells. METHODS: The lentiviral vector expressing HO-1 was prepared and transfected into apoptotic ARPE-19 cells induced by H2O2. Functional experiments including cell counting kit-8 (CCK-8) assay, flow cytometry (FCM) and mitochondrial membrane potential assay were conducted. RESULTS: The ultrastructure of ARPE-19 cells was observed using transmission electron microscope (TEM). It was found that exogenous HO-1 significantly ameliorated H2O2-induced loss of cell viability, apoptosis and intracellular levels of reactive oxygen species (ROS) in ARPE-19 cells. The overexpression of HO-1 facilitated the transfer of nuclear factor erythroid-2-related factor 2 (Nrf2) from cytoplasm to nucleus, which in turn upregualted expressions HO-1 and B-cell lymphoma-2 (Bcl-2). Furthermore, HO-1 upregulation further inhibited H2O2-induced release of cysteinyl aspartate specific proteinase-3 (caspase-3). CONCLUSION: Exogenous HO-1 protect ARPE-19 cells against H2O2-induced oxidative stress by regulating the expressions of Nrf2, HO-1, Bcl-2, and caspase-3.

miR-92b promotes gastric cancer growth by activating the DAB2IP-mediated PI3K/AKT signalling pathway.

OBJECTIVES: miR-92b has been reported to play critical roles in several carcinomas; however, our understanding of the mechanisms by which miR-92b stimulates gastric cancer (GC) is incomplete. The aim of this study was to investigate the clinical significance and functional relevance of miR-92b in GC. MATERIALS AND METHODS: Expression of miR-92b in GC and peritumoural tissues was determined using qRT-PCR, in situ hybridization and bioinformatics. CCK-8, colony formation and fluorescence-activated cell sorting assays were utilized to explore the effect of miR-92b on GC cells. A luciferase reporter assay and Western blotting were employed to verify miR-92b targeting of DAB2IP. Furthermore, Western blotting was used to evaluate the levels of DAB2IP and PI3K/Akt signalling pathway-related proteins. RESULTS: In this study, we found that miR-92b was upregulated in GC tissues compared with peritumoural tissues. Overexpression of miR-92b promoted cell proliferation, colony formation, and G0 /G1 transition and decreased apoptosis. Our results indicated that miR-92b repressed the expression of DAB2IP and that loss of DAB2IP activated the PI3K/AKT signalling pathway. Overexpression of DAB2IP rescued the effects of miR-92b in GC cells. Finally, our results demonstrated a significant correlation between miR-92b expression and DAB2IP expression in GC tissues. CONCLUSIONS: Our results suggest that miR-92b promotes GC cell proliferation by activating the DAB2IP-mediated PI3K/AKT signalling pathway. The miR-92b/DAB2IP/PI3K/AKT signalling axis may be a potential therapeutic target to prevent GC progression.

MicroRNA-497 regulates cell proliferation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. MicroRNA-497 (miR-497) is known to be downregulated in several types of human cancer; however, the expression, function and underlying mechanisms of miR-497 in HCC remain unclear. Therefore, the present study investigated miR-497 expression in HCC samples and HCC-derived cell lines using reverse transcription-quantitative polymerase chain reaction. The protein expression of one of the predicted common targets of miR-497, insulin-like growth factor-1 receptor (IGF-1R), was assessed using western blot analyses and immunohistochemistry. The role of miR-497 in regulating the proliferation of HCC-derived cells was also investigated in vitro and in vivo. Of 60 paired specimens from HCC patients, miR-497 was downregulated in 42 cancer specimens compared with adjacent non-cancer tissues. Western blotting and immunohistochemical analyses revealed that IGF-1R expression was significantly increased in HCC compared to control tissues. In addition, overexpression of miR-497 was observed to inhibit colony formation and tumor growth in MHCC-97H human HCC cells. Conversely, SMMC-7721 human HCC cells transfected with a miR-497 inhibitor exhibited enhanced colony formation and tumor growth. Finally, IGF-1R protein, phosphoinositide 3-kinase/Akt signaling pathway-associated proteins and cyclin pathway-associated proteins were differentially expressed between miR-497-overexpressing cells and miR-497-silenced cells. These results indicate that miR-497 may be a potentially effective gene therapy target.

Targeting MACC1 by RNA interference inhibits proliferation and invasion of bladder urothelial carcinoma in T24 cells.

The purpose of this article is to research on whether MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma (BUC). In this study, the expression of MACC1 gene was knocked down by RNA interference (RNAi) in the T24 cell (human BUC cell). The transcription level of MACC1 was detected by RT-PCR. Activities of MACC1, caspase-3, caspase-8, Bax and Met (mesenchymal-epithelial transition factor) protein were measured by Western blot. The cell proliferation and apoptosis were detected by MTT and flow cytometry. The cell's invasion ability was performed on Matrigel transwell assay. We also detect MMP2 (metalloproteinase-2) proteins by ELISA. The results showed that the level of MACC1 mRNA and protein was significantly reduced after RNAi. MTT assay showed that the proliferation of T24 cell was decreased due to RNA interference. Apoptosis studies also showed that MACC1 gene interference in T24 loses its anti-apoptotic effects. The expression of apoptosis proteins (Caspase-3, Caspase-8 and Bax) increased significantly due to the MACC1 RNAi. The level of Met protein was down-regulated obviously due to RNAi. Transwell assay showed that invasion abilities of T24 cells were reduced obviously due to MACC1 RNAi. Further studies showed that the secretion of MMP-2 was reduced by RNAi. It can conclude that the ability of proliferation and invasion in T24 cells can be inhibited by RNAi-targeting MACC1. As a result, MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma.

Cortactin promotes colon cancer progression by regulating ERK pathway.

Cortactin is upregulated in various cancers including breast cancer, head and neck squamous cell carcinoma and gastric cancer. However, the role of cortactin in the pathogenesis of colon cancer remains unclear. mRNA expression of cortactin in colon cancer samples and cell lines was detected by quantitative real-time PCR (qRT-PCR), while protein expression of cortactin in colon cancer tissues and adjacent non-cancer tissues was assessed by immunohistochemistry. The role of cortactin in regulation of the proliferation of colon cancer derived cells were investigated both in vitro and in vivo. In the total of 60 paired colon cancer specimens, compared with the adjacent non-cancer tissues, the expression of cortactin mRNA was upregulated in 45 (75.0%). Immunohistochemical analysis showed significantly increased cortactin expression in colon cancer (42/60, 70.0%) compared to control tissues (18/60, 30.0%). Overexpression of cortactin promoted HCT116 cellular colony formation and tumor growth. Conversely, cortactin knockdown inhibited these effects in SW480 cells. Mechanistic analyses indicated that cortactin was able to activate the EGFR-ERK signaling pathway. Additionally, cortactin expression was associated with tumor size, tumor stages and lymphatic invasion, increased cortactin expression predicts poor prognosis in patients with colon cancer. In summary, cortactin demonstrated the promotive effect in human colon cancer cell growth and tumorigenicity. These results indicated that cortactin may serve as an effective target for gene therapy.

Latexin exhibits tumor suppressor potential in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and latexin is downregulated in several types of human cancer. However, latexin expression in HCC remains unknown. mRNA expression of latexin in HCC samples and HCC-derived cell lines was detected by semi­quantitative PCR and real-time PCR, while protein expression was assessed by immunohistochemistry. The role of latexin in the regulation of the proliferation of HCC-derived cells was investigated both in vitro and in vivo. Flow cytometry was used to differentiate cell cycle distribution in SK-hep-1 and YY-8103. In a total of 60 paired HCC specimens, compared with adjacent non-cancer tissues, latexin mRNA was downregulated in 42 specimens. Immunohistochemical analysis showed a significant reduction in latexin expression in HCC compared to control tissues. Overexpression of latexin inhibited SK-hep-1 and HepG2 cellular colony formation and tumor growth. Conversely, YY­8103 and Focus cells transfected with shRNA enhanced colony formation and tumor growth. Latexin overexpression promoted cell cycle arrest in the G0/G1 phase in SK-hep-1 and silencing of latexin promoted the cell cycle transition from G0/G1 phase to S phase in YY-8103. The cyclin-dependent kinase inhibitors (CDKIs) (p21Cip1, p27Kip1, p15INK4B), cyclin D1 and cyclin E were shown to be differentially expressed in latexin-overexpressed cells and latexin-silenced cells. These results indicated that latexin may be an effective target for gene therapy.

Dermatomyositis associated with gallbladder carcinoma: A case report.

Patients with gallbladder carcinoma can present with a variety of paraneoplastic syndromes, including Cushing's syndrome, hypercalcemia, acanthosis nigricans, bullous pemphigoid, dermatomyositis and the sign of Leser-Trélat. Surgical resection of the primary tumor results in resolution of these paraneoplastic syndromes. We present a 67-year old female with facial and cervical erythema who was initially diagnosed with dermatomyositis. However, an abdominal computed tomography (CT) and positron emission tomography-CT scan was suspicious for gallbladder carcinoma with lymph node metastasis. After surgical resection, her dermatomyositis was resolved. This case demonstrates that dermatomyositis may be a manifestation of preexisting gallbladder carcinoma.