Relationship between the Cell Death-Inducing DNA Fragmentation Factor 45-Like Effector Protein Family and the Risk of Dyslipidemia.

According to the research, obesity is associated with hyperlipidemia, hypertension, and type 2 diabetes mellitus, which are grouped as metabolic syndrome. Notably, under the obese status, the adipocyte could accumulate excessive lipid as lipid droplets (LDs), leading the dysfunctional fat mass. Recently, emerging evidence has shown that the cell death-inducing DNA fragmentation factor 45-like effector protein (CIDE) family played an important role in regulating lipid metabolism. In addition, diverse CIDE proteins were also confirmed to influence the intracellular lipid metabolism, such as within adipocyte, hepatocyte, and macrophage. Nevertheless, the results which showed the regulatory influence of CIDE proteins are significantly contradictory from in vitro experiments and in vivo clinical studies. Similarly, recent studies have changed the perception of these proteins, redefining them as regulators of lipid droplet dynamics and fat metabolism, which contribute to a healthy metabolic phenotype in humans. However, the underlying mechanisms by which the diverse CIDE proteins alter lipid metabolism are not elucidated. In the current review, the understandings of CIDE proteins in lipid catabolism were well-summarized. On the other hand, the relatively mechanisms were also proposed for the further understandings of the CIDE protein family.

HDL regulates the risk of cardiometabolic and inflammatory-related diseases: Focusing on cholesterol efflux capacity.

Dyslipidemia, characterized by higher serum concentrations of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglyceride (TG), and lower serum concentrations of high-density lipoprotein cholesterol (HDL-C), is confirmed as a hallmark of cardiovascular diseases (CVD), posing serious risks to the future health of humans. Aside from the role of HDL-C concentrations, the capacity of cholesterol efflux to HDL is being identified as an enssential messurement for the dyslipidemic morbidity. Through inducing the progression of reverse cholesterol transport (RCT), the HDL-related cholesterol efflux plays a vital role in atherosclerotic plaque formation. In addition, increasing results demonstrated that the relationships between cholesterol efflux and cardiovascular events might be influenced by multiple factors, such as atherosclerosis, diabetes, and, inflammatory diseases. These risk factors could affect the intracellular composition of HDL, which might subsqently influence the cholesterol efflux process induced by HDL particle. In the present comprehensive article, we summarize the latest findings which described the modulatory roles of HDL in cardiometabolic disorders and inflammatory related diseases, focusing on its capacity in mediating cholesterol efflux. Moreover, the potential mechanisms whereby HDL regulate the risk of cardiometabolic disorders or inflammatory related diseases, at least partly, via cholesterol efflux pathway, are also well-listed.

New insights of acylation stimulating protein in modulating the pathological progression of metabolic syndromes.

Obesity is associated with insulin resistance, hypertension, and coronary artery diseases which are grouped as metabolic syndrome. Rather than being a storage for energy, the adipocytes could synthesis and secret diverse hormones and molecules, named as adipokines. Under obese status, the adipocytes are dysfunctional with excessively producing the inflammatory related cytokines, such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor α (TNF-α). Concerning on the vital role of adipokines, it is proposed that one of the critical pathological factors of obesity is the dysfunctional adipocytic pathways. Among these adipokines, acylation stimulating protein, as an adipokine synthesized by adipocytes during the process of cell differentiation, is shown to activate the metabolism of triglyceride (TG) by regulating the catabolism of glucose and free fatty acid (FFA). Recent attention has paid to explore the underlying mechanism whereby acylation stimulating protein influences the biological function of adipocyte and the pathological development of obesity. In the present review, we summarized the progression of acylation stimulating protein in modulating the physiological and hormonal catabolism which affects fat distribution. Furthermore, the potential mechanisms which acylation stimulating protein regulates the metabolism of adipose tissue and the process of metabolic syndrome were also summarized.

Relationship between inflammatory-related cytokines with aortic dissection.

Aortic dissection, characterized by severe intramural hematoma formation and acute endometrial rupture, is caused by excessive bleeding within the aortic wall or a severe tear within the intimal layer of the aorta, which subsequently promotes the separation or dissection in the layers of the aortic wall. Epidemiological surveys showed that aortic dissection was most observed among those patients from 55 to 80 years of age, with a prevalence of approximately 40 cases per 100,000 individuals per year, posing serious risks to future health and leading to high mortality. Other risk factors of aortic dissection progression contained dyslipidemia, hypertension, and genetic disorders, such as Marfan syndrome. Currently, emerging evidence indicates the pathological progression of aortic dissection is significantly complicated, which is correlated with the aberrant infiltration of pro-inflammatory cells into the aortic wall, subsequently facilitating the apoptosis of vascular smooth muscle cells (VSMCs) and inducing the aberrant expression of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interferon (IF). Other pro-inflammatory-related cytokines, including the colony-stimulating factor (CSF), chemotactic factor, and growth factor (GF), played an essential function in facilitating aortic dissection. Multiple studies focused on the important relationship between pro-inflammatory cytokines and aortic dissection, which could deepen the understanding of aortic dissection and further guide the therapeutic strategies in clinical practice. The present review elucidated pro-inflammatory cytokines' functions in modulating the risk of aortic dissection are summarized. Moreover, the emerging evidence that aimed to elucidate the potential mechanisms wherebyvarious pro-inflammatory cytokines affected the pathological development of aortic dissection was also listed.

Inflammatory Progression in Patients Undergoing Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is identified as a novel therapeutic strategy that offers short-term support to the metabolism of the heart and lungs in humans. Recently, the clinical centers, which provide ECMO has increased rapidly worldwide. The indications for the use of ECMO in daily clinical practice were broadened dynamically. However, even with the widespread adoption of ECMO, it still remains significant morbidity and mortality, and the underlying mechanisms are still not elucidated. Notably, one of the vital complications during ECMO was proposed as the inflammatory progression within the extracorporeal circulation. Via the development of inflammatory response, patients with ECMO may further suffer from systemic inflammatory response syndrome (SIRS), posing serious risks to human health. Recently, growing evidence confirmed that through exposure of blood into the ECMO circuit could lead to the stimulation of the immune system which also facilitated the inflammatory response and systemic impaired. In the current review, the pathological development of inflammatory progression in patients with ECMO is well-listed. Furthermore, the relationship between immune-related activation and the development of inflammation is also summarized, which may further help us to decide the therapeutic strategies in daily clinical practice.

Molecular Linkage under the Bicuspid Aortic Valve with Dyslipidemia.

Dyslipidemia is correlated with diverse cardiovascular problems, such as obesity, hypertension, and atherosclerosis, which are summarized as metabolic syndrome. Bicuspid aortic valve (BAV), as one of the congenital heart defects, is shown to influence approximately 2.2% of the general population worldwide, inducing the severe pathological development of aortic valve stenosis (AVS) or aortic valve regurgitation (AVR), and also to aortic dilatation. Notably, emerging evidence showed that BAV was correlated with not only the aortic valve and wall diseases but also the dyslipidemic related cardiovascular disorders. Recent results also proposed that multiple potential molecular mechanisms inducing the progression of dyslipidemia played important roles in BAV and the progression of AVS. Several altered serum biomarkers under dyslipidemic condition, including higher low-density lipoprotein cholesterol (LDL-C), higher lipoprotein (a) [Lp(a)], lower high-density lipoprotein cholesterol (HDL-C), and different pro-inflammatory signaling pathways, have proposed to embrace a vital function in the development of BAV correlated cardiovascular diseases. In this review, different molecular mechanisms which embrace an important role in personalized prognosis in the subjects with BAV was summarized. The illustration of those mechanisms might facilitate an accurate follow-up for patients with BAV and give new pharmacological strategies to improve development of dyslipidemia and BAV.

Novel Insights into the Important Role of Leptin in Modulating the Pathological Development of Fibrotic-related Diseases.

Leptin, as one of the most important cytokines within the circulation, has been confirmed to play a vital role in the hypothalamus of the central nervous system (CNS), which could modulate energy homeostasis by suppressing food intake. Furthermore, leptin could also influence cell metabolism by acting directly on the leptin receptor, which is a relatively small peptide and is mainly produced and released by fat tissue in mammals. On the other hand, the excessive extracellular matrix (ECM) could induce damage in normal tissues or organ structures, which might further induce fibrotic development in multiple tissues or organs, including the liver, heart, and kidneys. Notably, the sustainable development of fibrosis promotes the structural lesion and functional decline of different organs, which subsequently threatens human health and poses serious risks to human life. Emerging evidence has shown that leptin plays an important role in the fibrotic progression within multiple tissues and organs in mammals and has an alleviating effect on fibrosis. Concerning this notion, it has been proposed that leptin could be identified as a vital therapeutic strategy for fibrotic progression in clinical practice. Consequently, this review summarized the potential mechanisms of leptin in modulating fibrotic development in diverse tissues and organs to provide a theoretical basis for treating fibrotic-related diseases. In addition, the potential mechanisms whereby leptin affects the development of fibrosis were also summarized in the current review.

[Significance of Morphological Examination, Cytochemical Staining Combined with Bone Marrow Biopsy in Differential Diagnosis of Myelodysplastic Syndrome with Low Blasts and Hemolytic Anemia].

OBJECTIVE: To explore the value of morphological examination, cytochemical staining combined with bone marrow biopsy in the differential diagnosis between myelodysplastic syndrome (MDS) with low blasts and hemolytic anemia (HA). METHODS: The clinical data of 85 cases of myelodysplastic syndrome with low blasts (< 5%) and 61 patients with hemolytic anemia in Chinese PLA's Gerneral hospital from September 2009 to March 2015 were retrospectively analysed. The clinical characteristics, cytogenetic and molecular features, bone marrow cell count and morphology features, cytochemical staining results and bone marrow biopsy features of above-methioned patients were compared. RESULTS: There was no significant difference (P > 0.05) in clinical data between MDS group and HA group. Megakaryocytic dysplasia-positive rate, and ring sideroblasts positive rate, and PAS positive rate were significantly higher in MDS group than those that in HA group (P < 0.05). Abnormal localization of immature precursors (ALIP) and megakaryocytic dysplasia positive rate in bone marrow biopsy were significantly higher in MDS group than those that in HA group (P < 0.05), 90.6% of MDS with low blasts patients were identifiable by combined detections. CONCLUSION: Combining detection of morphology, cytochemistry staining and bone marrow biopsy has been confirmed to be more useful for differential diagnosis between MDS with low blasts and HA.

Quantitative Detection of ID4 Gene Aberrant Methylation in the Differentiation of Myelodysplastic Syndrome from Aplastic Anemia.

BACKGROUND: The diagnosis of myelodysplastic syndrome (MDS), especially hypoplastic MDS, and MDS with low blast counts or normal karyotype may be problematic. This study characterized ID4 gene methylation in patients with MDS and aplastic anemia (AA). METHODS: The methylation status of ID4 was analyzed by bisulfite sequencing polymerase chain reaction (PCR) and quantitative real-time methylation-specific PCR (MethyLight PCR) in 100 patients with MDS and 31 patients with AA. RESULTS: The MDS group had a higher ID4 gene methylation positivity rate (22.22%) and higher methylation levels (0.21 [0-3.79]) than the AA group (P < 0.05). Furthermore, there were significant differences between the hypoplastic MDS and AA groups, the MDS with low blast count and the AA groups, and the MDS with normal karyotype and the AA groups. The combination of genetic and epigenetic markers was used in much more patients with MDS (62.5% [35/56]) than the use of genetic markers only (51.79% [29/56]). CONCLUSIONS: These results showed that the detection of ID4 methylation positivity rates and levels could be a useful biomarker for MDS diagnosis.

[Clinical Implications on ZO-1 Gene Methylation in Myelodysplastic Syndrome Progression].

OBJECTIVE: To investigate the clinical significance of ZO-1 gene methylation level in MDS progression in order to provide a theoretical basis for evaluating progrosis of MDS patients. METHODS: The methylation specific PCR (MS-PCR) was performed to evaluate the ZO-1 gene methylation status in bone marrow samples of normal persons as control (NC). MDS and AML patients, the bisulfite sequencing PCR (BSP) was applied to detect the ZO-1 gene methylation status in serial bone marrow samples of MDS-RA, MDS-RAEB and AML stages of a MDS patients. RESULTS: The possitive rate of ZO-1 gene methylation in samples of NC, MDS and AML patients displayed significant difference; in sample of NC group the positive of ZO-1 gene methylation was not observed, but the positive rate of ZO-1 gene methylation in samples of AML patients was highest (65.0%), the proportion of ZO-1 gene methylation in myeloid blast count of MDS/AML patients was higher (P=0.000). The serial samples in one MDS patient showed that along with progress of disease, the positive rate of ZO-1 gene methylation in MDS-RA, MDS-RAEB and AML stages was found to be obvious different (P=0.000), the positive rate of ZO-1 gene methylation in AML stage was highest (64.65%). CONCLUSION: The high methylation in promoter region of ZO-1 gene has been found in MDS/AML patients, and along with clonal proliferation, the positive rate of ZO-1 methylation and positive froguency of methylation sites increase graduatly which suggests that the MDS progresses in a certain degree, and the ZO-1 gene methylation level may be used as an new indicator for monitoring desease progression from MDS to AML.

[Clinical significance of bone marrow morphological examination and tumor marker detection for lymphoma diagnosis and prognosis].

OBJECTIVE: This study was aimed to evaluate the significance of bone marrow(BM) morphological examination and many tumor marker(TM) detection, especially carcinoembryonic antigen (CEA), cancer antigen 125(CA125), cancer antigen 15-3 (CA15-3) and serum ferritin (SF) for lymphoma diagnosis and prognosis. METHODS: A total of 47 confirmed patients with lymphoma in our hospital from January 2012 to October 2013 and 20 health peoplels as normal controls were performed with bone marrow morphological examination, at the same time, the electrochemistry luminescent technique was applied for detecting levels of TM (especially CEA, CA125, CA15-3 and SF) in serum samples of lymphoma patient and normal controls, then the BM immature lymphocyte counts of these people and clinical parameters were analyzed for diagnosis and prognosis. RESULTS: There was significant differences in all the four TM levels between serum samples of lymphoma patients and normal control (P=0.029, P=0.000, P=0.005, P=0.000). These TM levels had no correlation with age, sex white blood cell, lymphocyte, platelet counts and anemia of lymphoma patients (P>0.05). It was also found that the patients with elevated TM levels had high BM immature lymphocytes (lymphoma cells) counts, B symptoms, advanced clinical stage and high IPI index (P<0.05). The CA15-3 and SF levels in serum samples of lymphoma patients with BM infiltration were higher than that in lymphoma patients without BM infiltration (P=0.002, P=0.000). CONCLUSION: Combination of BM morphological examination with serum TM level detection plays an important role in diagnosis, clinical stage and prognosis evaluation of lymphoma patients. It is also very important for assessing BM infiltration status of lymphoma patients.

[Clinical Significance of ID4 Gene Mehtylation in Demethylation-Treated MDS Cell Line and 2 MDS Patients].

OBJECTIVE: To evaluate significance of ID4 gene mehtylation in demethylating myelodysplastic syndrome(MDS) cell Line MUTZ1 and 2 patients with MDS. METHODS: The methylation-specific PCR (MS-PCR) and reverse transcription-PCR (RT-PCR) were applied to identify the methylation status and gene expression of ID4 gene in MDS cell line MUTZ1, a patient with aplastic anemia(AA) and a donor with normal bone marrow (NBM). RT-PCR was applied to detect the ID4 gene expression status in MUTZ1 cell line treated with decitabine at 3 different concentrations. Then bisulfite sequencing PCR (BSP) was applied to detect ID4 gene methylation status in 2 MDS parients treated with decitabine. RESULTS: The MDS cell line MUTZ-1 displayed a complete methylation of ID4 gene promoter with little mRNA expression. Inversely, bone marrow of an AA patient and NBM showed complete unmethylation of this gene with intensity mRNA expression. With the increase of decitabine concentration, ID4 gene mRNA expression was more and more increased. After decitabine treatment, ID4 gene methylation-positive frequencies of both the 2 MDS patients were much more decreased than that of the first treatment. So, ID4 gene mRNA expression inhibited by promoter hypemethylation could be recovered by using demethylation medicine. CONCLUSION: ID4 as a new potential anti-oncogene suggests that its methylation may become a marker for selection and assessment of therapeutic schedules in patients with MDS.

Clinical implications of the quantitative detection of ID4 gene methylation in myelodysplastic syndrome.

BACKGROUND: Myelodysplastic syndrome (MDS) eventually transforms into acute leukemia (AL) in about 30% of patients. Hypermethylation of the inhibitor of DNA binding 4 (ID4) gene may play an important role in the initiation and development of MDS and AL. The aim of this study was to quantitatively assess ID4 gene methylation in MDS and to establish if it could be an effective method of evaluating MDS disease progression. METHODS: We examined 142 bone marrow samples from MDS patients, healthy donors and MDS-AL patients using bisulfite sequencing PCR and quantitative real-time methylation-specific PCR. The ID4 methylation rates and levels were assessed. RESULTS: ID4 methylation occurred in 27 patients (27/100). ID4 gene methylation was more frequent and at higher levels in patients with advanced disease stages and in high-risk subgroups according to WHO (P < 0.001, P < 0.001, respectively) and International Prognostic Scoring System (IPSS) (P = 0.002, P = 0.007, respectively) classifications. ID4 methylation levels changed during disease progression. Both methylation rates and methylation levels were significantly different between healthy donor, MDS patients and patients with MDS-AL (P < 0.001, P < 0.001, respectively). Multivariate analysis indicated that the level of ID4 methylation was an independent factor influencing overall survival. Patients with MDS showed decreased survival time with increased ID4 methylation levels (P = 0.011, hazard ratio (HR) = 2.371). Patients with ID4 methylation had shorter survival time than those without ID4 methylation (P = 0.008). CONCLUSIONS: Our findings suggest that ID4 gene methylation might be a new biomarker for MDS monitoring and the detection of minimal residual disease.

Procalcitonin could be a reliable marker in differential diagnosis of post-implantation syndrome and infection after percutaneous endovascular aortic repair.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) is an emerging treatment modality, which has been rapidly embraced by clinicians treating thoracic aortic disease. However, the clinical manifestations of systemic inflammatory response after TEVAR as post-implantation syndrome (PIS) resemble the perioperative infection. This study aimed to evaluate changes and diagnostic value of procalcitonin (PCT) and other traditional inflammatory markers for infections after TEVAR. METHODS: We conducted a prospective clinical study that enrolled 162 consecutive aortic dissection cases, who underwent TEVAR in our institution between July 2011 and November 2012. The PCT, C-response protein (CRP), erythrocyte sedimentation rate (ESR) and blood routine examination were monitored before the operation and on days 1, 2, 3 and 5 after the operation. The diagnosis of infection was confirmed by the infection control committee with reference to Hospital Acquired Infection Diagnostic Criteria Assessment, released by the Ministry of Health of the People's Republic of China. RESULTS: Post endovascular repair of thoracic aorta, PCT changes significantly at different time points (χ(2) = 13.225, P = 0.021), without significant difference between the PIS group and the control group (0.24 ± 0.04 vs.0.26 ± 0.10, P = 0.804). PCT values were significantly higher in the first day after TEVAR than the preoperative levels (0.18 ± 0.03 vs. 0.11 ± 0.02, P < 0.001). Compared with PIS patients, the level of PCT, CRP, White blood cell (WBC) and neutrophil (NEU) in the infection patients elevated significantly (relatively χ(2) = 6.062, P = 0.048; χ(2) = 6.081, P = 0.048; χ(2) = 11.030, P = 0.004; χ(2) = 14.632, P = 0.001). According to the ROC analysis, the PCT levels in the first day after TEVAR (AUC = 0.785, P = 0.012) had better predictive values of infection than WBC, NEU CRP and ESR (AUC = 0.720, P = 0.040; AUC = 0.715, P = 0.045; AUC = 0.663, P = 0.274; AUC = 0.502, P = 0.991). The best predictive index was the changes of PCT between preoperative and postoperative (PCT), which possess AUC as 0.803 (P = 0.014). And PCT = 0.055 could be considered as an infection diagnosis cutoff value with a sensitivity of 83.3% and specificity 69.0%. CONCLUSIONS: PCT provides better diagnostic value of infection compared with other inflammatory markers. The potential applications of PCT in differential diagnosis of PIS and infection after percutaneous TEVAR deserve further studies.

[Clinical significance of ID4 methylation detection by quantitative methylation-specific PCR in acute leukemia].

The advances of treatment improved the prognosis of the patients with acute leukemia (AL) in the last decade, but the lack of general biomarker for predicting relapse in AL, which is one of the most important factors influencing the survival and prognosis. DNA methylation of ID4 gene promoter occurred frequently in patients with AL and was found to be highly related to the tumor progression. Based on the previous work of the setup of methylation-specific quantitative PCR system for ID4 gene, this study was designed to investigate the relation between the quantitative indicator of methylation density, percentage of methylation reference(PMR) value, and different disease status of AL. PMR of ID4 was detected by MS-PCR in bone marrow (BM) samples of 17 healthy persons and 54 AL patients in the status of newly diagnosis, complete remission and disease relapse. The results showed that at different disease status, PMR value in newly diagnosed group was significantly lower than that in complete remission group (P = 0.031). Among serial samples, PMR value remained very low at the status of patients with continuous complete remission (<1.5‰), and increased along with the accumulation of tumor cells at relapse. In 1 relapse case, the abnormal rise of PMR value occurred prior to morphological relapse. PMR value seemed to be related to body tumor cell load. It is concluded that the quantitative indicator of methylation density and PMR value may reflect the change of tumor cell load in acute leukemia patients. Dynamic monitoring of PMR maybe predict leukemia relapse.

[Establishment of methylation-specific quantitative PCR system for ID4 gene in acute leukemia cells and its specificity and sensitivity].

DNA methylation of ID4 gene promoter occurred frequently in patients with acute leukemia and was found to be highly related to the tumor progression. Due to lack of the appropriate methylation detection methods, the relation between the quantification of ID4 methylation and the states of acute leukemia is still unclear. This study purposed to set up a methylation-specific quantitative PCR system for ID4 and investigate the specificity and sensitivity of this methylation detection. The plasmids combined with target gene as well as with internal reference were constructed, and the standard curves were set up by using above mentioned plasmids. The specificity of this detection system in cell lines was verified through techniques of MSP and quantitative MSP. The sensitivity of this detection system was verified by mixing methylation-positive and negative cell lines in varying proportions and through amplification of qualitative MSP. The results showed that the standard curves were establish successfully. The results of quantitative MS-PCR in cell lines were consistent with those of MS-PCR, and as low as 1: 10(-5) of ID4 methylation positive cells could be detected by the new methylation detection assay. In newly diagnosed acute leukemia patients, the positive rate of quantitative MSP was higher. It is concluded that a complete quantitative MSP system for ID4 methylation detection has been established and this quantitative MSP method has good specificity and high sensitivity.

Perioperative aortic dissection rupture after endovascular stent graft placement for treatment of type B dissection.

BACKGROUND: The perioperative aortic dissection (AD) rupture is a severe event after endovascular stent graft placement for treatment of type B AD. However, this life-threatening complication has not undergone systematic investigation. The aim of the study is to discuss the reasons of AD rupture after the procedure. METHODS: The medical record data of 563 Stanford type B AD patients who received thoracic endovascular repair from 2004 to December 2011 at our institution were collected and analyzed. Double entry and consistency checking were performed with Epidata software. RESULTS: Twelve patients died during the perioperation after thoracic endovascular repair, with an incidence of 2.1%, 66.6% were caused by aortic rupture and half of the aortic rupture deaths were caused by retrograde type A AD. In our study, 74% of the non-rupture surviving patients had the free-flow bare spring proximal stent implanted, compared with 100% of the aortic rupture patients (74% vs. 100%, P = 0.213). The aortic rupture patients are more likely to have ascending aortic diameters = 4 cm (62.5% vs. 9.0%, P = 0.032), involvement the aortic arch concavity (62% vs. 27%, P = 0.041) and have had multiple stents placed (P = 0.039). CONCLUSIONS: Thoracic AD endovascular repair is a safe and effective treatment option for AD with relative low in-hospital mortality. AD rupture may be more common in arch stent-graft patients with an ascending aortic diameter = 4 cm and with severe dissection that needs multi-stent placement. Attention should be paid to a proximal bare spring stent that has a higher probability of inducing an AD rupture. Post balloon dilation should be performed with serious caution, particularly for the migration during dilation.

Association between lymphoma prognosis and aberrant methylation of ID4 and ZO-1 in bone marrow and paraffin-embedded lymphoma tissues of treatment-naive patients.

The aim of the present study was to investigate the association between lymphoma prognosis and aberrant methylation of inhibitor of DNA binding factor 4 (ID4) and tight junction protein 1 (ZO-1) genes in samples isolated from the bone marrow and paraffin-embedded lymphoma tissues of treatment-naive lymphoma patients. The bone marrow biopsy and paraffin-embedded lymphoma tissue samples from treatment-naive lymphoma patients were obtained, along with corresponding control samples from subjects without lymphoma and from lymph nodes of chronic cholecystitis and reactive lymphadenitis patients. Methylation-specific PCR (MSP) reactions were performed to analyze the methylation status on the promoter regions of ID4 and ZO-1. ID4 and ZO-1 promoter regions in the control group were completely unmethylated, whereas the rates of methylation of ID4 and ZO-1 in paraffin-embedded lymphoma tissues of the lymphoma patients were 80.4 and 84.3%, respectively. The methylation positivity rates of both the ID4 or ZO-1 genes in lymphoma patients were 92.2%, which was significantly higher compared to the rates in the control group (0%). The methylation positivity rates of the ID4 and ZO-1 genes in the bone marrow and paraffin-embedded lymphoma tissues of non-Hodgkin lymphoma patients were significantly higher compared to the rates in the Hodgkin lymphoma patients. The survival rate of lymphoma patients with methylated ID4 was significantly lower compared to that of patients with unmethylated ID4. The methylation of the ID4 and ZO-1 genes may be a specific molecular marker for lymphoma diagnosis. The methylation of the ID4 gene may be an indicator of poor prognosis in lymphoma patients.

[Poliovirus receptor on surface of acute B lymphoid leukemia cells modulated by epigenetic mechanism].

The aim of this study was to identify if the expression of poliovirus receptor (PVR) on the surface of acute B lymphoid leukemia (B-ALL) cells RS4:11 and SUP-B15 is modulated by epigenetic mechanism. B-ALL cell lines RS4:11 and SUP-B15 were treated with demethylation agent. Bisulfite PCR was performed to detect percentage change of the methylated CpG islands in the promoter region of PVR. In the meantime, the expression levels of PVR at the translation and transcription levels were detected by flow cytometry and RT-PCR respectively. The B-ALL cell lines were also treated with histone deacetylase (HDAC) inhibitor. The expression level of the gene mRNA and protein was detected too. The results indicated that after treated with 5-azacytidine, the hypermethylated status of PVR promoter region was partly reversed, and the expression of PVR at both mRNA and protein levels was restored in the meanwhile. HDAC inhibitor suberoylanilide hydroxamic acid could also increase the PVR expression. But there was no synergistic function between hypermethylation and HDAC as for repressing PVR transcription in B-ALL cell lines. It is concluded that the expression of PVR in B-ALL cells is modulated by epigenetic mechanisms. Treatment with corresponding inhibitors can partly restore the gene's expression in both mRNA and protein levels.