Targeting the chromatin structural changes of antitumor immunity.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

Catalase-only nanoparticles prepared by shear alone: Characteristics, activity and stability evaluation.

Catalase is a promising therapeutic enzyme; however, it carries risks of inactivation and rapid degradation when it is used in practical bioprocess, such as delivery in vivo. To overcome the issue, we made catalase-only nanoparticles using shear stress alone at a moderate shear rate of 217s(-1) in a coaxial cylinder flow cell. Properties of nanoparticles, including particle size, polydispersity index and zeta potential, were characterized. The conformational changes of pre- and post-sheared catalase were determined using spectroscopy techniques. The results indicated that the conformational changes of catalase and reduction in α-helical content caused by shear alone were less significant than that by desolvation method. Catalase-only nanoparticles prepared by single shear retained over 90% of its initial activity when compared with the native catalase. Catalase nanoparticles lost only 20% of the activity when stored in phosphate buffer solution for 72h at 4°C, whereas native catalase lost 53% under the same condition. Especially, the activity of nanogranulated catalase was decreased only slightly in the simulated intestinal fluid containing α-chymotrypsin during 4h incubation at 37°C, implying that the catalase nanoparticle was more resistant to the degradation of proteases than native catalase molecules. Overall, catalase-only nanoparticles offered a great potential to stabilize enzymes for various pharmaceutical applications.

[Association of leptin level and leptin receptor gene polymorphisms with susceptibility to severe pre-eclampsia].

OBJECTIVE: To evaluate the association of serum leptin concentrations and polymorphisms of G1019A and A223G of leptin receptor gene (LEPR) with severe pre-eclampsia. MEHTODS: A case-control study was carried out in 207 patients with severe pre-eclampsia (SPE group) and 252 healthy pregnant women (control group) during the third trimester of pregnancy. The serum leptin was determined by enzyme-linked immunosorbent assay. The polymorphisms of LEPR gene G1019A and A223G were detected by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP) analysis. Miettinen's test was used to estimate the odds ratios (OR) and 95% confidence intervals (CI). RESULTS: (1) In severe pre-eclampsia group, serum leptin levels and rate of premature infant birth were significantly higher than that in normal pregnant women, and birth weight was lower than that in controls (P<0.01). (2) The frequencies of GA genotype and G allele for LEPR gene G1019A in SPE group (33.8% and 20.3%) were markedly higher than that in controls (19.8% and 15.1%) (P<0.01), and the carriers of GA genotype and G allele were more frequent in SPE group than in control group, resulting in an OR 2.04 (95%CI: 0.77-5.42) and 1.43 (95%CI: 1.02-2.01) to develop severe pre-eclampsia, compared with carriers of AA genotype and A allele. (3) AG genotype and A allele frequencies of LEPR gene A223G in SPE group (19.3% and 12.6%) were significantly lower than that in controls (34.5% and 19.2%) (P<0.01), resulting in an OR of 0.46 (95%CI: 0.30-0.71) and 0.60 (95%CI: 0.42-0.87) to develop severe pre-eclampsia, compared with subjects with GG genotype and G allele. (4) The "1019AA+223AG" genotype frequency was significantly lower in SPE group (6.8%) than in controls (24.6%) (P<0.01), resulting in an OR of 0.22 (95%CI: 0.12-0.39) to develop severe pr-eclampsia, while the "1019AA+223AG" was significantly higher in SPE group (22.2%) than in controls (11.9%) (P<0.05), resulting in an OR of 2.10 (95%CI: 0.78-3.45) to develop severe pre-eclampsia. (5) No significant differences were found in SBP, DBP, BMI and serum leptin levels in subjects with different genotypes in the two groups (P>0.05). CONCLUSION: Elevated serum leptin level and LEPR gene G1019A and A223G polymorphisms might play a role in severe pre-eclampsia, while the level of serum leptin was not associated with genotypes of LEPR gene G1019A and A223G polymorphisms. The genotypes GA and "1019AA+223AG"of G1019A may be genetic susceptibility factors to severe pre-eclampsia.

[Association of genetic polymorphisms in plasminogen activator inhibitor-1 gene and 5,10-methylenetetrahydrofolate reductase gene with recurrent early spontaneous abortion].

OBJECTIVE: To explore the relationship of plasminogen activator inhibitor-1 (PAI-1) gene-675 4G/5G and methylenetetrahydrofolate reductase(MTHFR) gene C677T polymorphisms to recurrent early spontaneous abortion(RESA). METHODS: One hundred and twenty-seven currently non-pregnant women with at least 3 unexplained spontaneous abortions during the first trimester of pregnancy (patient group). Normal control group consisted of 117 currently non-pregnant women with at least 1 pregnancy and without a history of prematurity, miscarriage, stillbirth, eclampsia and other pregnancy complications. The genotypes of PAI-1 gene and MTHFR gene were assessed by polymerase chain reaction-restrictive fragment length polymorphism. RESULTS: The frequencies of 4G/4G genotype and 4G allele of PAI-1 were higher in patient group (45.7% and 66.1%) than in normal controls (17.1% and 46.6%) (P < 0.01). The PAI-1 4G/4G genotype was significantly associated with RESA (OR = 4.8, 95% CI: 2.23 - 10.35). Besides, MTHFR gene T/T genotype and T allele frequencies were increased in RESA patients (43.3% and 66.5%) versus normal controls (21.4% and 52.6%) (P < 0.01). The patients carrying T/T genotype had a high risk of early spontaneous abortion (OR = 3.2, 95% CI: 1.40 - 7.30). In additionìthe presence of the PAI-1 gene 4G/4G genotype together with the T/T genotype of the MTHFR gene was found to be a risk factor (OR = 6.20, 95% CI: 2.62 - 14.67) for RESA greater than the 4G/4G genotype or the T/T genotype alone. CONCLUSION: The above findings suggest that genetic polymorphisms of PAI-1 4G/5G and MTHFR C677T were associated with RESA. They may have synergetic impact and present gene dosage effect on the susceptibility to the development of early spontaneous abortion.

[Relationship between the 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene and the pathogenesis of pregnancy-induced hypertension syndrome].

OBJECTIVE: To investigate the relationship between a single nucleotide insertion/deletion(4G/5G) polymorphism located in the promoter region of the plasminogen activator inhibitor-1(PAI-1) gene and the pathogenesis of pregnancy-induced hypertension syndrome(PIHs). METHODS: The 4G/5G polymorphism of PAI-1 gene in 171 PIHs patients (PIHs group) and that in 193 normal pregnant women (control group) were detected by a combination of polymerase chain reaction-restriction fragment length polymorphism. RESULTS: (1)The genotype frequencies of PAI-1 gene in PIHs group were 47.4% for 4G/4G, 41.5% for 4G/5G, and 11.1% for 5G/5G. The 4G/4G genotype and 4G allele frequencies of PAI-1 gene(47.4% and 0.681) for PIHs patients were higher than those (21.2% and 0.495) for normal controls respectively (P<0.001). (2)Both the 4G/4G genotype and the 4G allele of PAI-1 gene occurred more frequently in the severe PIHs group(61.3% and 0.758) than those (35.8% and 0.623) in the mild PIHs group respectively (P<0.001). However, there were no significant differences between those in mild group (35.8% and 0.623) and moderate group(42.8% and 0.625) respectively. (3) The 4G/4G genotype was significantly associated with PIHs (OR=3.34, 95%CI: 2.14-5.22). CONCLUSION: These findings suggested that PAI-1 gene polymorphism may be a susceptible factor to the pathogenesis of PIHs and the 4G/4G genotype may be one of the major risk factors for PIHs in pregnant women.