Blood&Genomics

Nanoparticle interactions with blood proteins and what it means: a tutorial review

Erik Reimhult

2019, 3(2): 73-87. doi: 10.46701/APJBG.2019022019129

Abstract(1447) PDF(3887KB)(1357)

Abstract:
Nanoparticles find many uses in medicine and biomedical technology. Such applications imply that they must be colloidally stable and do not interact with proteins in the blood or blood serum. A nanoparticle put into the blood will instantaneously be covered by a protein corona that compromises the function of the nanoparticle core, changes the effective size of the nanoparticle, and determines its biological fate. Strategies developed to gain control over nanoparticles in biological fluids, particular in blood, heavily rely on creating a hydrated polymer shell that sterically and osmotically prevents a protein corona from forming. In this tutorial review, we provide an overview of factors that affect the formation of the protein corona in blood and how to prevent it forming. We focus on describing the latest advances in our understanding of how small core-shell nanoparticles (core diameter 4-20 nm in diameter) with a shell of densely grafted polymer chains, a so-called polymer brush, interact with proteins and cells in vitro. Such nanoparticles are among the most well-defined and well-characterized colloids used for biomedical applications, from which an improved understanding of how nanoparticle architecture influences their biological fate can be obtained in detail.

Genomic instability in Multiple Myeloma-relevance for Clinical Outcome and Efficacy of Therapy

Fumou Sun, Yan Cheng, Siegfried Janz

2019, 3(2): 89-99. doi: 10.46701/APJBG.2019022019126

Abstract(877) PDF(511KB)(1019)

Abstract:
Genomic instability is a driving force in the natural history of blood cancers including multiple myeloma,an incurable neoplasm of immunoglobulin producing plasma cells that reside in the hematopoietic bone marrow. Long recognized manifestations of genomic instability in myeloma at the cytogenetic level include abnormal chromosome numbers (aneuploidy) caused by trisomy of odd-numbered chromosomes; recurrent oncogene-activating chromosomal translocations that involve immunoglobulin loci; and large-scale amplifications, inversions, and insertions / deletions (indels). Catastrophic genetic rearrangements that either shatter and illegitimately reassemble a single chromosome (chromotripsis) or lead to disordered segmental rearrangements of multiple chromosomes (chromoplexy) also occur. Genomic instability at the nucleotide level results in base substitution mutations and small indels that affect both the coding and non-coding genome. Distinctive signatures of somatic mutations that can be attributed to defects in DNA repair pathways, the DNA damage response or aberrant activity of mutator genes including members of the APOBEC family have been identified. Here we review recent findings on genomic stability control in myeloma that are not only relevant for myeloma development and progression, but also underpin disease relapse and acquisition of drug resistance in patients with myeloma.

Advances in ABO gene expression regulation

Xiaoya Yang, Gengyin Wang

2019, 3(2): 101-107. doi: 10.46701/APJBG.2019022019125

Abstract(988) PDF(277KB)(771)

Abstract:
The ABO blood group system is vital to blood transfusion and organ transplantation. ABO antigens are the most important of all blood group antigens in clinical practice, and are not only present in red blood cells and platelets, but also in most secretions and epithelial tissues. ABO antigens are known to undergo drastic changes during the development, differentiation, and maturation of normal cells. Profound changes have also been documented in pathological processes such as tumorigenesis. To elucidate the molecular basis of how ABO genes are controlled in cell type specific expressions, such as normal cell differentiation or in cancer cells lacking A/B antigens, it is essential to understand the regulatory mechanisms of ABO gene expression. In this review, current knowledge concerning the regulatory mechanisms of ABO gene expression was summarized.

Iron stores in Chinese eligible male plateletpheresis donors

Lei Shao, Jinhua Wang, Shaowen Zhu, Hong Lin

2019, 3(2): 109-114. doi: 10.46701/APJBG.2019022019115

Abstract(924) PDF(324KB)(963)

Abstract:
Plateletpheresis donors may become iron deficient, particularly if donating at the maximum suggested interval of every 2 weeks. This study aimed to evaluate iron stores in male Chinese plateletpheresis donors. Serum samples were collected from 445 male plateletpheresis donors and serum ferritin (SF) levels were measured. There were 16 repeat donors (3.6%) with iron deficiency (SF<10 ng/mL), but none was found in first time donors. About 63 (14.2%) had depleted iron stores (SF<30 ng/mL), including two first time donors (0.4%). Repeat donors had lower mean SF levels than the first donors. There was a positive correlation between iron deficiency/depletion prevalence, lower hemoglobin level and number of platelet donations. Donation interval, age and ABO blood groups were not associated with iron status. Iron status needs to be monitored in repeat platepheresis donors and donors with Hb<130 g/L, especially when the number of donations are between 10 and 30. For these individuals, SF measurement and iron supplementation are recommended.

An establishment of the procedures to eliminate incorrect blood due to non-matched or mislabeled tubes

He Ziyi, Wang Qing, Chen Shaobin, Yu Lin, Chen Qingkai

2019, 3(2): 115-119. doi: 10.46701/APJBG.2019022019113

Abstract(569) PDF(273KB)(766)

Abstract:
This study aims to establish a set of procedures to eliminate incorrect blood due to non-matched tubes or mislabeled tubes. The errors such as these are suspected to have occurred when upon first and second-detection. Under the identical laboratory conditions, the results of re-detection of blood bag samples and rare type antigen samples, as well as re-collected samples from donor, and plasma diluted are not consistent with the original results. Here, 20 antigen erythrocytes were detected for blood bag samples and original samples, in which no incorrect blood was mistakenly administered or mislabeled. Samples taken under identical laboratory conditions were not found to have incorrect blood administered to a non-matched tube. The results showed nonlinear changes by HBsAg ELSIA after plasma dilution. The study suggests that the second-detection taken shortly after first detection is the most appropriate method to detect errors at the earliest time point. Blood bag samples are identical to those of the original antigen identification group, which means that the probability of the samples coming from the same donor is extremely highly. At same time, space and plasma diluted, re-detection can effectively exclude incorrect blood being added to a non-matched tube.

An analysis of intraoperative blood transfusion of cardiac surgery in one hospital from 2014 to 2016

Sihua Yi, Cuicui Chai, , Jing Lin, Hongliang Zhang, Qiangjun Luo, Han Wang, Jiangbo Chen, Dan Li

2019, 3(2): 121-124. doi: 10.46701/APJBG.2019022019122

Abstract(617) PDF(259KB)(692)

Abstract:
To investigate the usage of blood componentsfor cardiac surgery inthe First Hospital of Lanzhou University, data from January 2014 to December 2016 were collected for analysis, including the number of cardiac surgeries and blood transfusions. There were 1 589 males and 1 076 females, aged from 1 to 73 years, with an average age of (53.97 ± 11.33) years, in this study. The results showed that the rate of blood-free surgery in the hospital increased year by year,while the proportion of blood-used operation to total operations decreased every year. The ratio of plasma and platelets used in cardiac surgery decreased, while the cryoprecipitate ratio used in cardiac surgery increased. This study indicates that the transfusion medical level in cardiac surgery is improved continuously, and that the infusion of blood components has become more secure, efficient and rational.

Association between polymorphism of the cyclin E1 gene and susceptibility to hepatocellular carcinoma in Chinese Han population of Hubei

Qing Liu, Jiayan Ling, Qilong Song, Xiaodong Li, Chizhi Zhang, Mingzhong Xiao, Jie Huang, Shuxia Han, Ling Liu, Xiaoming Peng, Jie Tan, Yu Wang, Li Ouyang, Youyun Zhao, Jianhua Wu

2019, 3(2): 125-131. doi: 10.46701/APJBG.2019022019118

Abstract(679) PDF(671KB)(779)

Abstract:
This study aimed to explore the relationship between CCNE1 gene single nucleotide polymorphisms (SNP rs1406 and rs3218038) and the incidence of hepatitis B virus-related hepatocellular carcinoma (HCC) in the Chinese Han population in Hubei. A total of 663 subjects, including 173 HCC patients, 172 HBV-related liver cirrhosis (LC) patients, 162 asymptomatic HBV carriers (AsC), and 156 healthy controls, participated in the study. Genotyping of CCNE1 rs1406 and rs3218038 polymorphisms was done by illumina second generation sequence method.Our findings showed that rs1406 G>T variant decreased the risk of HCC (OR 0.710, P=0.035 G vs T), and no significant differences were found between rs3218038 SNP and HCC risk using the χ² test. Furthermore, stratified analysis revealed that differences in genotype frequencies were related to gender. Women who carried the CCNE1 GT genotype were significantly associated with a decreased risk of HCC, compared with healthy controls carrying the GG genotype (additive model, OR 0.378,P=0.030).The results suggest that the rs1406 G allele and CCNE1 rs1406 polymorphism produce an increased the risk of HCC in comparison with the T allele. Whereas, the GT genotype is a protective factor in the development of HCC in female patients.

HLA class II alleles with susceptibility of leprosy in the Mexican Mestizo population

Sergio Mercado Ceja, Lucia Rangel Gamboa, María Elisa Vega Memije, Angélica Olivo Díaz, Julio Granados

2019, 3(2): 133-137. doi: 10.46701/APJBG.2019022019117

Abstract(1097) PDF(309KB)(763)

Abstract:
Leprosy is a chronic, infectious disease, caused by Mycobacterium leprae, Mycobacterium lepromatosis or both, which affects the peripheral nervous system and the skin. Activation of cellular immunity in infected individuals depends on antigen recognition, which involves relevant HLA-Class II alleles. Therefore, the objective of this study was to determine HLA-Class II allele frequencies (HLA-DRB1and-DQB1)in Mexican Mestizo leprosy patients and compare themwith healthy controls, in order to define their role in the genetic susceptibility to this infection.The genomic DNA of each participant was obtained from peripheral blood, using the salting-out method. PCR amplification and hybridization ofHLA-class II alleleswas made by PCR-SSO. The results showed that frequencies of HLA-DRB1*15(Pc =0.003, OR=3.3 95%CI=1.53-7.33), HLA-DQB1*05(Pc =0.00003, OR=6.03 95%CI=2.49-14.61) and HLA-DQB1*06 (Pc =0.007, OR=2.89, 95%CI=1.38-6.04)were significantly higher among leprosypatients than those of healthy controls. The study suggests that HLA-DRB1*15, HLA-DQB1*05, and HLA-DQB1*06 are associated with leprosy susceptibility in the Mexican Mestizo population.

The role of free immunoglobulin light chains in serum from SLE patients with or without renal involvement

Julio Granados, Antonio Villa-Romero, Marcos Meneses Mayo, Miriam Santiago Ortíz, María Fernanda García Gutiérrez, Víctor Hugo Tovar Méndez, Daniela Ruiz Gómez, Susana Maricela Hernández Doo, Citlaly López Orozco, Adriana Aguirre Telio

2019, 3(2): 139-144. doi: 10.46701/APJBG.2019022019121

Abstract(807) PDF(493KB)(749)

Abstract:
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. Lupus nephritis (LN) affects 30% to 60% of adult Mexican patients. This study aimed to determine whether immunoglobulin free light chains (FLCs) constitute a biological marker for LN. FLCs have been previously studied as disease activity biomarkers, but patients with kidney damage are frequently excluded. A total of 75 consecutive SLE patients were recruited from a third-level hospital in Mexico City. Thirty-eight patients were diagnosed with LN, and the remaining 37 patients without kidney failure were included as a control group. FLCs concentration was measured by nephelometry. The results showed that SLE patients with high FLCs concentration had a higher rate of kidney failure and that the probability of renal failure increased by 2.4% for each mg/dL of κ FLCs, and 1.7% for each mg/dL of λ FLCs. This study suggests that high FLCs concentration is associated with LN, and therefore may be considered as a possible biomarker for SLE activity.

Eg5 high expression predicts dismal prognosis in epithelial ovarian cancer

Pingping Sun, Xuemin Cao, Yuanlin Liu, Lizhou Jia

2019, 3(2): 145-151. doi: 10.46701/APJBG.2019022019128

Abstract(662) PDF(776KB)(796)

Abstract:
The expression of kinesin spindle protein (Eg5) and its significance of clinical prognosis of patients with epithelial ovarian cancer (EOC) were evaluated in this study. Forty-five fresh frozen tissue samples for quantitative real-time polymerase chain reaction (qPCR) and 196 samples for immunohistochemistry (IHC) analysis with tissue microarray (TMA) were applied to characterize Eg5 mRNA and protein expressions in EOC. The correlation between clinical parameters and Eg5 protein expression was investigated using statistical analysis. The expression of Eg5 protein was significantly higher in EOC tissues compared with that in corresponding non-cancerous tissues (P < 0.05). The high Eg5 expression was significantly correlated with older age (P = 0.003), higher stage (P = 0.001), presence of metastasis (P = 0.041) and higher CA125 serum level (P = 0.013). For univariate analysis, associated prognostic markers in patients with ovarian cancer were analyzed for correlations with poor overall survival, including Eg5 (P = 0.011), age (P = 0.001), FIGO stage (P = 0.011), CA125 serum level (P = 0.001), lymph nodes (P = 0.012), and metastasis (P = 0.001). For multivariate analysis, Eg5 expression, FIGO stage and age were independent factors found contributing to a largely unfavorable prognosis in patients with ovarian cancer. In conclusion, the high expression of Eg5 is correlated with an unfavorable prognosis in EOC.

Myelodysplastic syndrome with ring sideroblasts, SF3B1 mutation and beta thalassemia trait: a case of report

Amin Hojat, Grace Kao, Monika Pilichowska

2019, 3(2): 153-155. doi: 10.46701/APJBG.2019022019120

Abstract(590) PDF(857KB)(763)

Abstract:

2019 Vol. 3, No. 2