Blood&Genomics

Macropinocytosis and SARS-CoV-2 cell entry

Xiaowei Sun, Wenyue Zheng, Rui Hua, Yujie Liu, Li Wang, Yun-Gi Kim, Xinqi Liu, Hitomi Mimuro, Zhongyang Shen, Lian Li, Sei Yoshida

2021, 5(1): 1-12. doi: 10.46701/BG.2021012021110

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Abstract:
Macropinocytosis is a type of large-scale endocytosis that is triggered by the interaction of receptor proteins and ligands, such as growth factors, cytokines, chemokines, and lipopolysaccharide (LPS). Macropinocytosis ingests the extracellular fluid solutes and conveys them into the lysosome in the context of cell growth and differentiation. Aside from its physiological functions, macropinocytosis has been observed in viral infections. While the infectious mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still unknown, recent studies suggest the involvement of macropinocytosis in its cell entry. In this review, we discuss the roles of endocytosis in SARS-CoV/SARS-CoV-2 cell entries and propose a hypothetical role of macropinocytosis in SARS-CoV-2 cell entry.

Screening of tumor-targeting peptides for diagnosis and therapy through phage display technology

Zhiruo Song, Yufeng Zhang, Yuanjie Zhu, Mingming Zhang, Xinjian Liu, Minjun Ji

2021, 5(1): 13-20. doi: 10.46701/BG.2021012021103

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Abstract:
Phage display technology was introduced by G. Smith in 1985, which is highly effective in the selection of affinity peptides from a library containing billions of display peptides. The obtained peptides show potential efficacy in the development of further clinical applications, especially in tumor treatment. In this review, the basic principles, limits, developments of phage display technology and peptide libraries are introduced. Following that, the amino acid sequence of tumor target peptides for hematological and other systems are discussed. Finally, the application of target peptides in the design of imaging probes and the development of target peptide drugs for diagnosis and therapy are noted.

Distribution of HLA class Ⅰ and class Ⅱ haplotypes in Chinese Han population based on family segregation

Lijun Wang, Wei Li, Dongmei Wang, Na Liu, Yanjun Jia

2021, 5(1): 21-28. doi: 10.46701/BG.2021012021109

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Abstract:
HLA haplotype analysis has important application value in human population genetics, anthropological research and HLA matching transplantation. Based on HLA-A, -B, -C, -DRB1 and -DQB1 genotyping data from 663 families including 663 leukemia patients and 991 related donors, the allele frequency (AF) and haplotype frequency (HF) of two-, three- and five-locus haplotype distribution patterns in the Chinese Han population were determined by family segregation. A total of 38 alleles at A locus, 75 alleles at B locus, 35 alleles at C locus, 53 alleles at DRB1 locus and 22 alleles at DQB1 locus were discovered in this population. The frequencies of these alleles were basically consistent with those of previous reports except for some tiny differences. The study found 11 A-C, 15 C-B, 4 B-DRB1 and 11 DRB1-DQB1 two-locus haplotypes with a frequency over 2%. The number of A-C-B and A-B-DRB1 three-locus haplotype with a frequency over 1% were 11 and 3 respectively. The most common HLA-A-C-B-DRB1-DQB1 haplotype (HF>1%) were A*3001-C*0602-B*1302-DR*0701-DQ*0202 (4.30%), A*0207-C*0102-B*4601-DR*0901-DQ*0303 (3.07%), A*3303-C*0302-B*5801-DR*0301-DQ*0201 (1.49%) and A*1101-C*0102-B*4601-DR*0901-DQ*0303 (1.01%). The results are helpful for finding matching donors for hematopoietic stem cell transplant patients and also contribute to transplant immunology, HLA-related diseases, research of human genetics and other fields.

Evidence for AJUBA-catenin-CDH4-linked differentiation resistance of mesenchymal stem cells implies tumorigenesis and progression of head and neck squamous cell carcinoma: a single-cell transcriptome approach

Andres Stucky, Li Gao, Lan Sun, Shengwen Calvin Li, Xuelian Chen, Tiffany H. Park, Jin Cai, Mustafa H. Kabeer, Xi Zhang, Uttam K. Sinha, Jiang F. Zhong

2021, 5(1): 29-39. doi: 10.46701/BG.2021012021106

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Abstract:
An increasing number of reports indicate that mesenchymal stem cells (MSCs) play an essential role in promoting tumorigenesis and progression of head and neck squamous cell carcinoma (HNSCC). However, the molecular mechanisms underlying this process remain unclear. Using the MSC model system, this study analyzes the molecular pathway by which differentiation resistant MSCs promote HNSCC. MSCs were cultured in osteogenic differentiation media and harvested on days 12 and 19. Cells were stained for cell differentiation analysis using Alizarin Red. The osteogenesis-resistant MSCs (OR-MSCs) and MSC-differentiation-derived osteoblasts (D-OSTBs) were identified and subjected to the single-cell transcriptome analysis. Gene-specific analyses of these two sub-populations were performed for the patterns of differential expression. A total of 1780 differentially expressed genes were determined to distinguish OR-MSCs significantly from D-OSTB. Notably, AJUBA, β-catenin, and CDH4 expression levels were upregulated considerably within the OR-MSCs compared to D-OSTBs. To confirm their clinical relevance, a survey of a clinical cohort revealed a high correlation among the expression levels of AJUBA, β-catenin and CDH4. The results shed new light that OR-MSCs participate in the development of HNSCC via a pathway mediated by AJUBA, β-catenin, CDH4, and CTNNB1, thereby implying that MSC-based therapy is a promising therapeutic approach in the management of HNSCC.

Comparative analysis of antibody responses to SARS-CoV-2 in various populations

Lei Liu, Wanbing Liu, Yan Liu, Guomei Kou, Yaqiong Zheng, Liping Cai, Shengdian Wang, Shangen Zheng

2021, 5(1): 41-47. doi: 10.46701/BG.2021012021102

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Abstract:
This paper aimed to analyze antibody responses to SARS-CoV-2 in various populations. Two hundred and six COVID-19 patients, 46 convalescent patients, and 270 healthy population were enrolled. Antibodies against nucleocapsid protein (N) and spike protein's receptor-binding domain (RBD), and neutralizing antibody were detected. The results demonstrated both anti-N and anti-RBD antibodies could be detected in about 80% of COVID-19 patients and 90% of convalescent patients, while no antibodies could be detected in some convalescents and patients even after 14 days post-onset of symptoms. The level of anti-RBD antibody strongly correlated with the neutralizing activity of sera from these two cohorts. The titer of neutralizing antibody was lower in convalescents than that in active COVID-19 patients. In addition, the titer of neutralizing antibody was less than 1:80 in none of the severe COVID-19 patients, 18.8% in non-severe COVID-19 patients, and 32.6% in convalescents. The study suggests that the level of anti-RBD antibody is closely related to neutralization activity in COVID-19 patients and convalescents. Some SARS-CoV-2-infected cases trigger a weak antiviral immune response, and the level of neutralizing antibody may have a faster decay rate.

Serological and genetic analysis of a rare CisAB01/O01 blood group

Xiaoyong Liu, Zhaodi Yi, Ming Gao, Haojun Zhang, Buqiang Wang, Hongjun Gao, Yi Wu, Yuping Chen

2021, 5(1): 48-52. doi: 10.46701/BG.2021012021101

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Abstract:
The paper aims to analyze a rare blood sample in Ganzhou City Hospital with CisAB subtype and explore a feasible pattern for blood typing of rare blood type patients, so as to ensure clinical transfusion safety. The routine serological methods were used for ABO forward and reverse blood typing and the fluorescence real-time PCR technique was used for sample genotyping. A human ABO blood group 6-7 exon sequencing kit was used for sequence analysis. The nucleic acid sequence of the sample was compared with reference sequences. The forward typing results demonstrated that the sample was ABw, RhD positive. The sample exhibited 4+ agglutination with anti-H and anti-AB antibodies. Reverse typing by microcolumn gel method showed an AB result, but the serum sample demonstrated weak agglutination with B cell under room temperature, 4 °C and 37 °C in saline when tested with tube method respectively. The serological results matched with the A₂B₃ serotype. The fluorescent real-time PCR genotyping results displayed A/O01. The sequence analysis demonstrated deletion of guanine in 261-position 467C>T (heterozygote) and 803G>T (heterozygote) mutation respectively. The mutation caused the A glycosyltransferase peptide chain to change from proline to leucine (P156L) at 156 and from glutamate to alanine (G268A) at 268. The result demonstrated that the sample's genotype was CisAB01/O01. The mutation of glycosyltransferase coding gene leads to an abnormal serological reaction pattern. Only by combining the results of genetic analysis can we get the true sample blood type and better ensure the safety of clinical blood transfusion.

Molecular genetic analysis of weak B blood group allele in Jinan population reveals distribution of ABw phenotype

Wen Wu, Xiaojian Li, Xingying Guo, Peng Wu, Xiangyan Huang

2021, 5(1): 53-56. doi: 10.46701/BG.2021012020130

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Abstract:
The aim of this study was to investigate the distribution of the ABw phenotype of ABO blood group in the Jinan population. 31 856 samples were tested during the period 2018 to 2019. Thirty-nine samples with discrepant results, as identified by micro-column gel method, were further investigated by serological (tube technique) and molecular (fluorescence PCR, DNA sequencing) methods. Eight samples showed ABw phenotype, which accounted for 0.025% of the population tested. From the sequencing analysis, six samples (6/8) were typed as ABO*A1.02/ABO*BW.12 and two samples (2/8) as ABO*A1.02/ABO*BW.03. The study suggests that ABw12 account for 75% of ABw phenotype and indicate ABw12 is the main ABw phenotype in Jinan population.

A massive dose of allogeneic platelet gel for wound hemostatic therapy on patients with giant thoracic aortic aneurysm: report of 2 cases

Jianjun Wu, Bin Jiang, Renxue Xiang, Ronghui Shi, Changsheng He, Kang Yang, Xin Cui, Shuming Zhao

2021, 5(1): 57-62. doi: 10.46701/BG.2021012021105

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Abstract:
Autologous platelet-rich plasma (PRP) or platelet gel (PG) has been widely used in clinical treatment. Allogeneic PRP or PG may also become a safe and effective alternative method. In this study, two cases with giant thoracic aortic aneurysm were reported where massive doses of allogeneic PG were used to spray the thoracic aortic aneurysm wall suture wrapped in artificial blood vessels, tumors blood vessel wall anastomotic site, and incision site of surgical operation. The volumes of 220 mL and 250 mL PG were applied on two patients respectively, to clot bleeding and decrease the mediastinal and pericardial drainage days after operation. The drainage tubes were pulled out on the 4^th day after operation. The patients were transferred from ICU to a cardiothoracic surgery ward on the 4^th and 5^th day respectively. This study suggests that allogeneic platelet concentrate, as a source of PRP to prepare PG, may be used to promote and help the clotting and wound healing on surgical operation.

Identification of a novel MYH9 mutation (p. V782Y) in a Chinese patient with thrombocytopenia: a case report

Yafei Tian, Yongping Zhang, Shaoyan Hu, Lilan Yao, Yijian Zhu, Shenglong Qiao, Daru Lu, Junjie Fan

2021, 5(1): 63-67. doi: 10.46701/BG.2021012021113

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Abstract:
MYH9-related diseases (MYH9-RD) are a group of autosomal dominant diseases caused by mutations in the MYH9 gene, which are featured by thrombocytopenia, giant platelets and granulocyte cytoplasmic inclusion bodies. MYH9-RD patients generally suffer from bleeding syndromes, progressive kidney disease, deafness, or cataracts. Here, we reported on a case of MYH9-RD. A novel heterozygous mutation of MYH9 (c.2344-2345delGTinsTA, p.T782Y) was discovered by targeted sequencing technology. Immunofluorescence analysis of neutrophils confirmed abnormal aggregation of MYH9 protein. The results of this study should expand the MYH9 gene mutation spectrum and provide reference for subsequent researchers and genetic counseling.

Impact of the sympathetic nervous system on multiple myeloma

Siegfried Janz

2021, 5(1): 68-72. doi: 10.46701/BG.2021012021107

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Abstract:

2021 Editorial Working Conference of Blood and Genomics Held in Chongqing

2021, 5(1): 72-72.

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Abstract:

2021 Vol. 5, No. 1