Overexpression of METTL14 mediates steatohepatitis and insulin resistance in mice.

Background: Lipid accumulation and redox imbalance, resulting from dysregulation of hepatic fatty acids oxidation, contribute to the development of steatohepatitis and insulin resistance. Recently, dysregulated RNA N6-methyladenosine (m6A) methylation modification has been found involving fatty liver. However, the role of methyltransferase-like 14 (METTL14), the core component of m6A methylation, in the development of steatohepatitis is unknown. Herein, we aimed to explore the role of METTL14 on steatohepatitis and insulin resistance in mice with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: The liver tissues of mice and patients with MASLD were collected to detect the expression of METTL14. METTL14 overexpression and METTL14 silence were used to investigate the effect of METTL14 on lipid metabolism disorder in vivo and in vitro. Knockout of METTL14 in primary hepatocytes was used to investigate the role of Sirtuin 1 (SIRT1) on lipid accumulation induced by METTL14. Results: METTL14 was dramatically up-regulated in the livers of db/db mice, high-fat diet (HFD)-fed mice, and patients with MASLD. METTL14 overexpression exacerbated MASLD and promoted lipid metabolism disorder and insulin resistance in mice. Conversely, METTL14 knockout ameliorated lipid deposition and insulin resistance in HFD-fed mice. Furthermore, METTL14 overexpression facilitated lipid accumulation, while METTL14 knockout reduced lipid accumulation in HepG2 cells and primary hepatocytes. In addition, METTL14 lost up-regulated SIRT1 expression in hepatocytes. SIRT1 deficiency abrogated the ameliorating effects of METTL14 downregulation in MASLD mice. Conclusions: These findings suggest that dysfunction of the METTL14-SIRT1 pathway might promote hepatic steatosis and insulin resistance.

Ectopically expressed IBP promotes cell proliferation in oral squamous cell carcinoma.

IFN regulatory factor 4 binding protein (IBP) has been shown to play an important role in the progression of malignant tumors such as breast cancer cells, but its function in oral squamous cell carcinoma (OSCC) remains unclear. We found that IBP ectopically expressed in some OSCC specimens but not in normal oral mucosa epithelium tissues. IBP expression was significantly correlated with tumor size, differentiation, clinical stage, and distant metastasis. Furthermore, IBP markedly promoted OSCC cell proliferation, shortened the G1 interval in the cell cycle, and increased cyclin D1 expression. These findings suggest that IBP may be a potential therapeutic target for OSCC.

Long noncoding RNA NNT-AS1 promotes hepatocellular carcinoma progression and metastasis through miR-363/CDK6 axis.

Long non-coding RNAs (lncRNAs) have been tested to act as important regulator in liver cancer genesis and progression. LncRNA Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) has been reported to participate in the tumorigenesis. However, the exact molecular mechanism of NNT-AS1 in hepatocellular carcinoma (HCC) is still unknown. In present study, our team identified the up-regulated expression of NNT-AS1 in HCC tissue and cell lines compared with adjacent noncancerous tissue and normal cells. Moreover, HCC patients with high NNT-AS1 levels had poor prognosis than that with low NNT-AS1 level (p=0.0089). In vitro, gain- and loss-of-function experiments revealed that enhanced NNT-AS1 expression promoted the proliferation ability and alleviated the cycle arrest and apoptosis, while NNT-AS1 knockdown suppressed the proliferation and induced G0/G1 phase arrest and apoptosis. In vivo, NNT-AS1 knockdown inhibited the HCC neoplastic tumor volume and weight. Bioinformatics analysis and luciferase reporter assay validated that miR-363 targeted NNT-AS1 and CDK6 3'-UTR. MiR-363 was down-regulated in HCC tissue and cells. NNT-AS1 competed with CDK6 for miR-363 binding and could increase CDK6 expression. In summary, our results suggest the oncogenic role of NNT-AS1 in HCC tumorigenesis through miR-363/CDK6 axis, providing a novel therapeutic target for human HCC.

Successful liver resection in a giant hemangioma with intestinal obstruction after embolization.

Hepatic hemangiomas are the most common benign tumor of the liver. Most hepatic hemangiomas remain asymptomatic and require no treatment. Giant hepatic hemangiomas with established complications, diagnostic uncertainty and incapacitating symptoms, however, are generally considered an absolute indication for surgical resection. We present a case of a giant hemangioma with intestinal obstruction following transcatheter arterial embolization, by which the volume of the hemangioma was significantly reduced, and it was completely resected by a left hepatectomy. A 21-year-old Asian man visited our hospital for left upper quadrant pain. Examinations at the first visit revealed a left liver hemangioma occupying the abdominal cavity, with a maximum diameter of 31.5 cm. Embolization of the left hepatic artery was performed and confirmed a decrease in its size. However, the patient was readmitted to our hospital one month after embolization for intestinal obstruction. A left hepatectomy was completed through a herringbone incision, and safely removed a giant hemangioma of 26.5 cm × 19.5 cm × 12.0 cm in size and 3690 g in weight. Pre-operative arterial embolization is effective for reducing tumor size, but a close follow-up to decide the time for hepatectomy is important.

[Isolation and identification of human periodontal ligament stem cells in vitro].

OBJECTIVE: To isolate and identify human periodontal ligament stem cells (PDLSC) by improved methods and assess the characteristics of PDLSC ex vivo. METHODS: The periodontal ligament cells were obtained from the healthy impacted third molars and teeth extracted for orthodontic purposes and used to isolate PDLSC by limiting dilution assay. PDLSC were cultured and expanded in alpha-MEM supplemented with 10% FBS. Colony-forming assay, immunohistochemistry, flow cytometry, osteogenic and adipogenic induction were used to identify PDLSC. RESULTS: The obtained cells had high colony-forming efficiency and were positive staining for vimentin and negative for pancytokeratin. Flow cytometry revealed that the isolated cells were positive for STRO-1 and CD146 antibodies and most were in the G0/G1 phase of cell cycle. Under specific conditions, they could differentiate to the osteoblast and adipocyte lineages in vitro. CONCLUSION: Limiting dilution assay is an effective method to isolate PDLSC and the single-cell-derived colonies demonstrate the properties of stem cells in vitro.

[Influence of bicortical anchorage on the natural frequencies of dental implant].

OBJECTIVE: To investigate the influences of bicortical anchorage on values of natural frequencies of dental implants utilizing the 3-dimensional finite element analysis. METHODS: Using the commercial code of Solidworks, 3-D models of a screw-shaped dental implant and a mandibular bone segment were generated. After the 3-D implant-bone complex was meshed by ABAQUS software, effects of bicortical anchorage on the buccolingual and axial first-order natural frequencies of the implant were computed. RESULTS: Bicortical anchorage increased both the buccolingual and axial natural frequencies remarkably. As the bicortical anchorage got deeper, the frequencies correspondingly got higher. CONCLUSION: Bicortical anchorage can increase the buccolingual and axial primary stability of dental implants.