Algal oil rich in n-3 polyunsaturated fatty acids suppresses B16F10 melanoma lung metastasis by autophagy induction.

Melanoma is a malignant tumor that arises from epidermal melanocytes with high morbidity and mortality, and currently, there are no effective conventional genotoxic treatments or systematic treatment. Increasing evidence shows that n-3 polyunsaturated fatty acids (PUFAs) exhibit anti-melanoma activity, but their anti-melanoma mechanism remains elusive. Here, C57BL/6 mice were injected with B16F10 melanoma cells via a tail vein to establish a lung metastasis model. n-3 PUFAs were significantly increased in lung metastatic tissues from mice treated with algal oil, especially rich in docosahexaenoic acid (DHA). Algal oil treatment significantly suppressed pulmonary metastases and outgrowth of melanoma cells, which was associated with autophagy induction, as evidenced by an increase in LC3-II levels. In addition, algae oil-triggered autophagy was mediated by inactivation of the mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein (MAP) kinase, and activation of c-Jun N-terminal kinases (JNKs), which led to a decrease in p62 accumulation and decreased secretion of proinflammatory cytokine interleukin-1ß (IL-1ß). These results suggest that algal oil exerts its antitumourigenic activities via autophagy-mediated p62 elimination and anti-inflammatory properties.

Mori Cortex extract ameliorates nonalcoholic fatty liver disease (NAFLD) and insulin resistance in high-fat-diet/streptozotocin-induced type 2 diabetes in rats.

Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg-1·d-1) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.

Efficacy of epalrestat plus α-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of α-lipoic acid (ALA) plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy (DPN). DATA SOURCES: The electronic databases of PubMed, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were (diabetic peripheral neuropathy or diabetic neuropathy or DPN) AND (α-lipoic acid or lipoic acid or thioctic acid) AND epalrestat. DATA SELECTION: All of the eligible studies met the following inclusion criteria: (1) Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN. (2) The minimum duration of treatment was 2 weeks. (3) The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria. (4) Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. OUTCOME MEASURES: The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV and peroneal SNCV. RESULTS: Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies (RR = 1.29, 95% CI: 1.21-1.38; RR = 1.43, 95% CI: 1.34-1.54, respectively). ALA plus epalrestat combination therapy also significantly improved median MNCV (WMD = 5.41, 95% CI: 2.07-8.75), median SNCV (WMD = 5.87, 95% CI: 1.52-10.22), peroneal MNCV (WMD = 5.59, 95% CI: 2.70-8.47) and peroneal SNCV (WMD = 4.57, 95% CI: 2.46-6.68). CONCLUSION: : ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies for clinical efficacy and nerve conduction velocities in patients with DPN.

Endogenously synthesized n-3 fatty acids in fat-1 transgenic mice prevent melanoma progression by increasing E-cadherin expression and inhibiting ß-catenin signaling.

Malignant melanoma is the most lethal form of skin cancer. Although preclinical studies have shown that n-3 polyunsaturated fatty acids (PUFAs) are beneficial for prevention of melanoma, the molecular mechanisms underlying the protective effects of n­3 PUFAs on melanoma remain largely unknown. In the present study, endogenously increased levels of n-3 PUFAs in the tumor tissues of omega­3 fatty acid desaturase (fat­1) transgenic mice was associated with a reduction in the growth rate of melanoma xenografts. This reduction in tumor growth in fat­1 mice compared with wild­type controls may have been associated, in part, to the: i) Increased expression of E­cadherin and the reduced expression of its transcriptional repressors, the zinc finger E­box binding homeobox 1 and snail family transcriptional repressor 1; ii) significant repression of the epidermal growth factor receptor/Akt/ß­catenin signaling pathway; and iii) formation of significant levels of n­3 PUFA­derived lipid mediators, particularly resolvin D2 and E1, maresin 1 and 15­hydroxyeicosapentaenoic acid. In addition, vitamin E administration counteracted n­3 PUFA­induced lipid peroxidation and enhanced the antitumor effect of n­3 PUFAs, which suggests that the protective role of n­3 PUFAs against melanoma is not mediated by n­3 PUFAs­induced lipid peroxidation. These results highlight a potential role of n­3 PUFAs supplementation for the chemoprevention of melanoma in high­risk individuals, and as a putative adjuvant agent in the treatment of malignant melanoma.

[The effect of environmental factors and DNA methylation on type 2 diabetes mellitus].

Type 2 diabetes mellitus (T2DM) is a glucose metabolic disorder driven by both genetic and environmental factors. Recent DNA methylation studies have established that T2DM may be contributed by environmental factors through the regulation of DNA methylation. Human and animal model studies have made much progress on the interaction between DNA methylation of T2DM genes and environmental factors in multiple tissues. Current studies on DNA methylation of T2DM genes mainly focus on glucose and energy metabolism, inflammation, and so on. This review comprehensively introduces the DNA methylation studies for the genes involved in T2DM and its related environmental factors.

[Phosphorylated JNK mediated apoptosis induced by all trans retinoid acid in human retinoblastoma cell line].

OBJECTIVE: To investigate the mechanism of all trans retinoid acid (ATRA) inhibition of cell growth and induction of apoptosis in human retinoblastoma Y79 cells. METHODS: Antiproliferating effects of ATRA on Y79 cells were studied by (3)H-thymidine incorporation. Cell cycle analysis was performed by flow cytometry, apoptosis of the ATRA-treated cells was determined by DNA fragmentation analysis and JNK phosphorylation analyzed by Western blot. RESULTS: After 36h treatment of 1 micro mol/L ATRA, (3)H-thymidine incorporation decreased to 40% with Y79 cells arrested in G(0)/G(1) and Sub-G(1) peak appeared. DNA ladder was observed in DNA fragmentation analysis after 36h treatment of ATRA. Curcumin, a JNK blocker, blocked the apoptosis and the growth inhibition induced by ATRA. JNK was phosphorylated in 10 to 20 min. CONCLUSION: ATRA can induce the apoptosis in Y79 cells by phosphorylation of JNK, which suggests that ATRA may have clinical application prospects for treatment of retinoblastoma.