Role of Vitamin D deficiency and mRNA expression of VDR and RXR in haematological cancers.

Vitamin D has a crucial role in cancer control and prevention. For its activity, VDR (vitamin D receptor) and its heterodimer RXR (Retinoid X receptor) are equally important in the cell. This ligand (vitamin D) and receptors (VDR-RXR) complex together triggers downstream DNA damage response in the cell and thus counters cancer in blood. 137 patients and 60 disease free controls were recruited for this study. The levels of vitamin D in patient and controls were analysed and compared using ELISA. The mRNA expression of the two receptor genes; VDR and RXR was also assessed by RT-PCR, to see their role in haematological malignancies. Their expression levels were corelated with the vitamin D levels in individuals to understand their mutual contribution in blood cancer prevention. The results confirmed a highly significant correlation between vitamin D levels of patients and controls (p < 0.001). The study also revealed that age of patients is a critical factor in determining the relative risk of blood cancer (p < 0.001), its types (leukaemia and lymphoma) and subtypes. Also, the mRNA expression of VDR showed a positive and non-significant relationship with vitamin D levels and RXR expression (p > 0.05). Based on our findings, and studies on other diseases it can be inferred that Vitamin D deficiency and dysregulation of its associated receptors may lead to cancer initiation and/or progression by failing to trigger the cellular DNA damage repair machinery.

Integrative plasma proteomic and microRNA analysis of Jersey cattle in response to high-altitude hypoxia.

Blood has been widely collected and analyzed for diagnosing and monitoring diseases in humans and animals; a range of plasma proteins and peptide can be used as biomarkers to describe pathological or physiological status. Changes in the environment such as high-altitude hypoxia (HAH) can lead to adaptive changes in the blood system of mammals. However, the adaptation mechanism induced by HAH remains unclear. In this study, we used 12 multiparous Jersey cattle (400 ± 35 kg, average 3 yr old, dry period). We applied an iTRAQ (isobaric tags for relative and absolute quantitation) proteomics approach and microRNA (miRNA) microarray to explore differences in the plasma proteomic and miRNA profiles of Jersey cattle exposed to HAH conditions in Nyingchi, Tibet (altitude 3,000 m) and HAH-free conditions in Shenyang, China (altitude 50 m). Such quantitative proteomic strategies are suitable for accurate and comprehensive prediction of miRNA targets. In total, 264 differentially expressed proteins (127 upregulated, fold-change >1.2; 137 downregulated, fold-change <0.8) and 47 differential miRNAs (25 upregulated, fold-change >2; 22 downregulated, fold-change <0.5) were observed in the HAH-stressed group compared with the HAH-free group. Integrative analysis of proteomic and miRNA profiles demonstrated that the biological processes associated with differentially expressed proteins were immune response, complement system, and conjugation system. Integrative analysis of canonical pathways showed that most were associated with acute phase response signaling (z-score = -0.125), liver X receptor/retinoid X receptor (LXR/RXR) activation pathway (z-score = 1.134), coagulation system (z-score = -0.943), and complement system (z-score = -0.632). The current results indicated that Jersey cattle exposed to HAH could adapt to that condition through regulation of inflammatory homeostasis by inhibiting the acute phase response, coagulation system, and complement system and promoting LXR/RXR activation.

Association of serum retinoic acid with hepatic steatosis and liver injury in nonalcoholic fatty liver disease.

BACKGROUND: Retinoic acid (RA), an active metabolite of vitamin A (retinol), has been implicated in the regulation of lipid metabolism and hepatic steatosis in animal models. However, the relation between RA and liver histology in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is unknown. OBJECTIVE: This study aimed at examining the association of RA with NAFLD and NASH in Chinese subjects. DESIGN: Serum RA concentration was determined by ELISA in 41 control subjects, 45 patients with NAFLD, and 38 patients with NASH. The associations of RA with adiposity, serum glucose, lipid profiles, and markers of liver damage were studied. Moreover, both mRNA and protein levels of retinoic X receptor α (RXRα) in the liver were analyzed in subjects with different degrees of hepatic steatosis. RESULTS: Serum RA concentrations in patients with NAFLD (1.42 ± 0.47 ng/mL) and NASH (1.14 ± 0.26 ng/mL) were significantly lower than those in control subjects (2.70 ± 0.52 ng/mL) (P < 0.01). Furthermore, serum RA concentrations were significantly different between subjects with normal glucose tolerance and those with type 2 diabetes in control [2.87 ± 0.52 (n = 28) vs. 2.32 ± 0.44 ng/mL (n = 13)], NAFLD [1.61 ± 0.37 (n = 29) vs. 1.28 ± 0.41 ng/mL (n = 16)], and NASH [1.35 ± 0.34 (n = 24) vs. 1.07 ± 0.29 ng/mL (n = 14)] groups. In human liver tissue, RXRα mRNA expression was inversely correlated with the exacerbation of hepatic steatosis. Both serum RA concentrations and RXRα mRNA levels were inversely correlated with intrahepatic triglyceride content (r = -0.700, P < 0.001, and r = -0.611, P = 0.002, respectively). Compared with grade 0 severity, the concentration of RXRα protein was lower in more severe grades in patients with NAFLD. CONCLUSION: These results show that circulating RA concentrations were lower in subjects with NAFLD and were associated with hepatic lipid metabolism and insulin resistance. This trial was registered at clinicaltrials.gov as NCT01940263.