Hydroxymethylation and tumors: can 5-hydroxymethylation be used as a marker for tumor diagnosis and treatment?

5-Methylcytosine (5mC) is considered as a common epigenetic modification that plays an important role in the regulation of gene expression. At the same time, 5-hydroxymethylcytosine (5hmC) has been found as an emerging modification of cytosine bases of recent years. Unlike 5mC, global 5hmC levels vary from tissues that have differential distribution both in mammalian tissues and in the genome. DNA hydroxymethylation is the process that 5mC oxidates into 5hmC with the catalysis of TET (ten-eleven translocation) enzymes. It is an essential option of DNA demethylation, which modulates gene expression by adjusting the DNA methylation level. Various factors can regulate the demethylation of DNA, such as environmental toxins and mental stress. In this review, we summarize the progress in the formation of 5hmC, and obtaining 5hmC in a cell-free DNA sample presents multiple advantages and challenges for the subject. Furthermore, the clinical potential for 5hmC modification in dealing with cancer early diagnosis, prognostic evaluation, and prediction of therapeutic effect is also mentioned.

Isoliquiritigenin Inhibits the Growth of Colorectal Cancer Cells through the ESR2/PI3K/AKT Signalling Pathway.

Colorectal cancer (CRC) is one of the most common malignancies. Isoliquiritigenin (ISL), a flavonoid phytoestrogen, has shown anti-tumour activities against various cancers. However, its anti-CRC mechanism has not been clarified. In this study, the potential molecular mechanism of ISL against CRC was investigated through network pharmacological prediction and experimental validation. The results of the network prediction indicate that ESR2, PIK3CG and GSK3ß might be the key targets of ISL against CRC, which was verified by molecular docking, and that its anti-tumour mechanisms might be related to the oestrogen and PI3K/AKT signalling pathway. The experimental results show that ISL reduced the viability of SW480 and HCT116 cells, induced apoptosis, blocked the cell cycle in the G2 phase in vitro, and suppressed xenograft tumour growth in vivo. In addition, ISL significantly down-regulated the protein expression of PIK3CG, AKT, p-AKT, p-GSK3ß, CDK1, NF-κB and Bcl-2; up-regulated ESR2 and Bax; decreased the ratio of p-AKT/AKT and p-GSK3ß/GSK3ß; and increased the Bax/Bcl-2 ratio. This study indicates that ISL can inhibit the growth of CRC cells and induce apoptosis, which may be related to the up-regulation of ESR2 and inhibition of the PI3K/Akt signalling pathway.

Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo.

Gastric cancer is reported as one of the leading factors resulting in tumor-related death worldwide. However, the therapies to suppress gastric cancer are still limited and the emergence of drug resistance makes it necessary to develop new and effective anticancer drugs and combinational chemotherapy schemes. Liquiritin (LIQ) is a major constituent of Glycyrrhiza Radix, exhibiting various pharmacological activities, including anticancer. In this study, we investigated the role of LIQ in human gastric cancer cells with cisplatin (DDP) resistance. The findings suggested that LIQ, when applied in single therapy, could moderately inhibit the proliferation and migration of DDP-resistant gastric cancer cells, SGC7901/DDP. DDP and LIQ in combination induced G0/G1 cell cycle arrest to suppress the proliferation of gastric cancer cells, which were associated with the decrease of cyclin D1, cyclin A and cyclin-dependent kinase 4 (CDK4) and increase of p53 and p21. In addition, LIQ combined with DDP significantly induce apoptosis and autophagy both in vitro and in vivo through enhancing cleavage of caspase-8/-9/-3 and PARP, as well as LC3B and Beclin 1 expression. Significantly, the two drugs, when used in combination, prevented gastric cancer cell xenografts in nude mice in vivo. Together, the results revealed that application of DDP and LIQ in combination possessed a potential value against the growth of human gastric cancer with DDP resistance.

Breastfeeding practices on postnatal wards in urban and rural areas of the Deyang region, Sichuan province of China.

BACKGROUND: Despite the efforts that have been made to promote breastfeeding in China since the 1990s, there is still a very low prevalence of exclusive breastfeeding. The objective of this study was to assess the current situation of infant feeding practices during the postpartum hospital stay in urban and rural areas of the Deyang region. METHODS: Cross-sectional sampling was used in two urban hospitals and five rural clinics in the Deyang region of southwestern China. Interviews with mothers after delivery (urban n = 102, rural n = 99) were conducted before discharge and five focus group discussions were held. RESULTS: The prevalence of Caesarean section was high in both urban and rural areas (63.9 % urban vs. 68.4 % rural). After birth, nearly all mothers (98.0 % urban vs. 99.0 % rural) initiated breastfeeding. One week after delivery, the prevalence of exclusive breastfeeding was 8.0 % (9.8 % urban vs. 6.1 % rural), almost exclusive breastfeeding 34.5 % (29.4 % urban vs. 39.8 % rural), mixed feeding 56.0 % (58.8 % urban vs. 53.1 % rural), and exclusive formula feeding 1.5 % (2.0 % urban vs. 1.0 % rural). Breastfeeding initiation (≤ two days after birth) was positively associated (Odds Ratio [OR] 1.97, 95 % Confidence Interval [CI] 1.11, 3.50) with exclusive and almost exclusive breastfeeding, whereas birth length under 50 cm (OR 0.48, 95 % CI 0.26, 0.87), mother's education > 12 years (OR 0.46, 95 % CI 0.24, 0.88) and mother's lack of knowledge about the importance of colostrum (OR 0.35, 95 % CI 0.14, 0.86) were negatively associated with almost exclusive breastfeeding. CONCLUSION: Although disparities between urban and rural areas exist, the situation of infant feeding is inadequate in both settings. The high prevalence of Caesarean section, the mothers' poor knowledge of the physiology of breast milk production, the mothers' lack of breastfeeding confidence, the widespread advertising of breast milk substitutes, and the changing perception of the function of breasts, may influence the unfavorable breastfeeding behavior observed in the study area.

Dietary intake and food habits of pregnant women residing in urban and rural areas of Deyang City, Sichuan Province, China.

Micronutrient deficiencies and imbalanced dietary intake tend to occur during the reproductive period among women in China. In accordance with traditional Chinese culture, pregnant women are commonly advised to follow a specific set of dietary precautions. The purpose of this study was to assess dietary intake data and identify risk factors for nutritional inadequacy in pregnant women from urban and rural areas of Deyang region, Sichuan province of China. Cross-sectional sampling was applied in two urban hospitals and five rural clinics (randomly selected) in Deyang region. Between July and October 2010, a total of 203 pregnant women in the third trimester, aged 19-42 years, were recruited on the basis of informed consent during antenatal clinic sessions. Semi-structured interviews on background information and 24-h dietary recalls were conducted. On the basis of self-reported height and pre-pregnancy weight, 68.7% of the women had a pre-pregnancy body mass index (BMI) within the normal range (18.5 ≤ BMI < 25), 26.3% were found to be underweight with a BMI <18.5 (20.8% in urban vs. 35.6% in rural areas), while only 5.1% were overweight with a BMI ≥30. In view of acceptable macronutrient distribution ranges (AMDRs) the women's overall dietary energy originated excessively from fat (39%), was low in carbohydrates (49.6%), and reached the lower limits for protein (12.1%). Compared to rural areas, women living in urban areas had significantly higher reference nutrient intake (RNI) fulfillment levels for energy (106.1% vs. 93.4%), fat (146.6% vs. 119.7%), protein (86.9% vs. 71.6%), vitamin A (94.3% vs. 65.2%), Zn (70.9% vs. 61.8%), Fe (56.3% vs. 48%), Ca (55.1% vs. 41%) and riboflavin (74.7% vs. 60%). The likelihood of pregnant women following traditional food recommendations, such as avoiding rabbit meat, beef and lamb, was higher in rural (80%) than in urban (65.1%) areas. In conclusion, culturally sensitive nutrition education sessions are necessary for both urban and rural women. The prevalence of underweight before conception and an insufficient supply of important micronutrients were more pronounced in rural areas. Therefore, attention must be given to the nutritional status, especially of rural women before, or at the latest, during pregnancy.