Long non-coding RNA ANRIL in gene regulation and its duality in atherosclerosis.

The antisense transcript long non-coding RNA (lncRNA) (antisense non-coding RNA in the INK4 locus, ANRIL) is an antisense of the cyclin-dependent kinase inhibitor 2B (CDKN2B) gene on chromosome 9p21 that contains an overlapping 299-bp region and shares a bidirectional promoter with alternate open reading frame (ARF). In the context of gene regulation, ANRIL is responsible for directly recruiting polycomb group (PcG) proteins, including polycomb repressive complex-1 (PRC-1) and polycomb repressive complex-2 (PRC-2), to modify the epigenetic chromatin state and subsequently inhibit gene expression in cis-regulation. On the other hand, previous reports have indicated that ANRIL is capable of binding to a specific site or sequence, including the Alu element, E2F transcription factor 1 (E2F1), and CCCTC-binding factor (CTCF), to achieve trans-regulation functions. In addition to its function in cell proliferation, adhesion and apoptosis, ANRIL is very closely associated with atherosclerosis- related diseases. The different transcripts and the SNPs that are related to atherosclerotic vascular diseases (ASVD-SNPs) are inextricably linked to the development and progression of atherosclerosis. Linear transcripts have been shown to be a risk factor for atherosclerosis, whereas circular transcripts are protective against atherosclerosis. Furthermore, ANRIL also acts as a component of the inflammatory pathway involved in the regulation of inflammation, which is considered to be one of the causes of atherosclerosis. Collectively, ANRIL plays an important role in the formation of atherosclerosis, and the artificial modification of ANRIL transcripts should be considered following the development of this disease.

Efficient generation of functional hepatocyte-like cells from mouse liver progenitor cells via indirect co-culture with immortalized human hepatic stellate cells.

BACKGROUND: Differentiation of liver progenitor cells (LPCs) to functional hepatocytes holds great potential to develop new strategies for hepatocyte transplantation and the screening of drug-induced cytotoxicity. However, reports on the efficient and convenient hepatic differentiation of LPCs to hepatocytes are few. The present study aims to investigate the possibility of generating functional hepatocytes from LPCs in an indirect co-culture system. METHODS: Mouse LPCs were co-cultured in Transwell plates with an immortalized human hepatic stellate cell line (HSC-Li) we previously established. The morphology, expression of hepatic markers, and functions of mouse LPC-derived cells were monitored and compared with those of conventionally cultured LPCs. RESULTS: Co-culturing with HSC-Li cells induced differentiation of mouse LPCs into functional hepatocyte-like cells. The differentiated cells were morphologically transformed into hepatocyte-like cells 3 days after co-culture initiation. In addition, the differentiated cells expressed liver-specific genes and possessed hepatic functions, including glycogen storage, low-density lipoprotein uptake, albumin secretion, urea synthesis, and cytochrome P450 1A2 enzymatic activity. CONCLUSIONS: Our method, which employs indirect co-culture with HSC-Li cells, can efficiently induce the differentiation of LPCs into functional hepatocytes. This finding suggests that this co-culture system can be a useful method for the efficient generation of functional hepatocytes from LPCs.

[Association between the serum TSH concentration and thyroid cancer incidence].

OBJECTIVE: To investigate the association between serum TSH concentration and thyroid cancer incidence. METHODS: Three hundred and thirty patients with thyroid tumors who underwent surgical treatment were included in this study (99 cases of malignancy and 231 cases of benign tumors). The data of their serum TSH level, gender, age, tumor type, and number of tumors detected by ultrasonic inspection were retrospectively analyzed, and their association with thyroid cancer incidence was explored. RESULTS: The proportion of thyroid cancer in the groups of younger than twenty years and older than seventy years were 63.0% and 58.3%, respectively, significantly higher than that in the group of age between 60 and 69 years (23.3%, P < 0.05). The incidence of thyroid cancer of the 81 male patients was 43.2%, significantly higher than that in the 249 female patients (25.7%, P = 0.003). The incidence of thyroid cancer in the 112 patients with single nodule was 42.0%, significantly higher than that in the 218 patients with multiple nodules (23.9%, P < 0.001). In the groups with TSH level lower than 0.28 mIU/L and higher than 4.20 mIU/L, the incidence of thyroid cancer were 54.6% and 50.0%, respectively, significantly higher than that in the group with TSH level between 0.28 and 1.44 mIU/L (16.1%, P < 0.05). The proportion of patients with thyroid cancer was also increased with the increasing serum TSH level in the normal range (P < 0.001). High serum TSH level (OR = 1.465, P = 0.014), male (OR = 1.964, P = 0.016) and a single thyroid nodule (OR = 2.090, P = 0.006) are independent risk factors of thyroid cancer. CONCLUSION: The high serum TSH level, male, single thyroid nodule are factors leading to a high incidence of thyroid cancer.