A research review of experimental animal models with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) consists of a group of hematologic tumors that are derived from the clonal proliferation of hematopoietic stem cells, featuring abnormal hematopoietic cell development and ineffective hematopoiesis. Animal models are an important scientific research platform that has been widely applied in the research of human diseases, especially tumors. Animal models with MDS can simulate characteristic human genetic variations and tumor phenotypes. They also provide a reliable platform for the exploration of the pathogenesis and diagnostic markers of MDS as well as for a drug efficacy evaluation. This paper reviews the research status of three animal models and a new spontaneous mouse model with MDS (AU)

A research review of experimental animal models with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) consists of a group of hematologic tumors that are derived from the clonal proliferation of hematopoietic stem cells, featuring abnormal hematopoietic cell development and ineffective hematopoiesis. Animal models are an important scientific research platform that has been widely applied in the research of human diseases, especially tumors. Animal models with MDS can simulate characteristic human genetic variations and tumor phenotypes. They also provide a reliable platform for the exploration of the pathogenesis and diagnostic markers of MDS as well as for a drug efficacy evaluation. This paper reviews the research status of three animal models and a new spontaneous mouse model with MDS.

[Serum Lipid Levels and Their Prognostic Significance in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the serum lipid levels and their prognostic significance in patients with multiple myeloma (MM). METHODS: A total of 87 newly diagnosed MM patients and 87 healthy controls in our hospital from January 2012 to April 2021 were selected. Serum lipid levels were compared between MM patients and healthy controls. The differences of serum lipid levels in patients among two groups of sex, age, hemoglobin (Hb), albumin (ALB), platelet (PLT), ß2-microglobulin (ß2-MG) and bone marrow plasma cell ratio (BMPC), different immune types, different ISS stages, before and after chemotherapy were analyzed. Univariate and COX multivariate regression analysis were used to analyze the influence of clinical parameters such as serum lipid indexes on prognosis of MM. RESULTS: The serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B) in MM patients were significantly lower than those in healthy controls (P<0.05). Anemia, low protein and low PLT in patients were related to low cholesterol. The levels of TC, LDL-C, HDL-C, Apo A1 and Apo B in patients with low Hb and ALB were significantly lower than those in patients with high Hb and ALB (P<0.05). The Apo B level of low PLT patients was significantly lower than that of high PLT patients (P<0.05). The levels of TC, LDL-C, HDL-C, Apo A1 and Apo B in patients with different immune types were significantly different, the above indexes of IgA type were significantly lower than IgG type(P<0.05), IgG type were significantly lower than light chain type(P<0.05), double clone type were significantly lower than light chain type (P<0.05). The levels of TC, LDL-C, and Apo B in patients with different ISS stages were significantly different, stage Ⅱ were lower than those of stage Ⅰ (P>0.05), stage Ⅲ were significantly lower than those of stage Ⅱ and stageⅠ(P<0.05). The levels of TC, TG, LDL-C, HDL-C, Apo A1 and Apo B in patients after chemotherapy were significantly higher than those before chemotherapy (P<0.05). Univariate analysis showed that Hb, PLT, ß2-MG, BMPC, LDL-C and Apo B affected the prognosis of MM. Multivariate analysis showed that BMPC and Apo B were independent factors affecting the prognosis of MM. CONCLUSION: The serum cholesterol level is decreased in MM patients, and hypocholesterolemia is related to the classification and staging of the disease. With the improvement of the disease, the serum cholesterol level is increased, and low serum Apo B level predicts a poor prognosis.

[The Types and Laboratory Characteristics of Non-Hodgkin Lymphoma with Bone Marrow Invasion as the First Manifestation].

OBJECTIVE: To investigate the types and laboratory characteristics of non-Hodgkin lymphoma(NHL) with bone marrow invasion as the first manifestation. METHODS: 81 non-Hodgkin lymphoma patients with bone marrow invasion as the first manifestation treated in our hospital from January 2010 to July 2019 were selected. The clinical features, blood routine, lactate dehydrogenase (LDH), EB virus results, bone marrow features, immunophenotyping, gene and genetic characteristics of all patients were analyzed retrospectivel. RESULTS: Among 81 patients, 73 cases(90%) were B-cell lymphoma, 5 cases(6%) were T-cell lymphoma and 3 cases(4%) were NK/T-cell lymphoma, while the mantle cell lymphoma and diffuse large B-cell lymphoma were the highest, which accounted for 21%(17 cases) and 19.7%(16 cases), and lymphoma accounted for 8.6%(7 cases). There were 44 cases(54.3%) showed B symptoms, 65 cases (80.2%) showed abnormal blood routine. The MYD88 gene was detected in 5 of 17 cases. 25 cases of patients underwent chromosome examination, the result showed that 5 cases were t(8; 14) (q24; q32), 3 cases were complex karyotype and 17 cases were normal karyotype. 23 cases(23.4%) were EB virus positive, 42 cases(51.9%) were LDH increased. The proportion of bone marrow lymphoma cells was 1%-92%. Among them, 32 cases were diagnosed as lymphoma leukemia, and 6 cases of bone marrow lymphoma cells showed mass distribution similar to extramedullary tumor cells with bone marrow metastasis. CONCLUSION: B-cell lymphoma is the predominant NHL with bone marrow invasion as the first manifestation, while mantle cell lymphoma and diffuse large B-cell lymphoma are the most common pathological types with blood routine abnormalities. Bone marrow lymphoma cells can also present clusters of bone marrow metastasis, different types of lymphoma cells can make directional diagnosis.

A base-repair based electrochemiluminescent genotoxicity sensor that detects abasic sites in double-stranded DNA films.

A novel genotoxicity sensor was developed based on the base repair process associated with the electrochemiluminescence (ECL) detection of abasic sites in a double-stranded DNA monolayer. This is the first time that an ECL sensor with the ability to identify the removed nucleobases in a DNA duplex has been studied. The successful detection of abasic sites created by DNA glycosylase indicates its further applications for examining some other specific types of DNA damage.

Distance-dependent quenching and enhancing of electrochemiluminescence from tris(2, 2'-bipyridine) ruthenium (II)/tripropylamine system by gold nanoparticles and its sensing applications.

Understanding the role of gold nanoparticles (AuNPs) in electrochemiluminescence (ECL) processes of the Ru(bpy)32+ (bpy= 2, 2'-bipyridine)/tripropylamine (TPA) system would be beneficial to develop novel ECL sensors for a variety of applications. In this work, we found that the AuNPs on the surface of indium tin oxide (ITO) electrode could catalyze the electrochemical oxidation of TPA, greatly enhancing the ECL signal of Ru(bpy)32+/TPA, present in the solution. If physical separation of AuNPs away from electrode surface after hybridization with target ssDNA, ECL signal decreased dramatically due to the loss of electrochemical activity of AuNPs, based on which a sensitive and specific DNA sensor in a "switch-off" mode was constructed with a detection limit of 0.2 pM. In addition, a suppressing effect of the AuNPs on the ECL of Ru(bpy)32+ was experimentally confirmed by decreasing the electrocatalytic effect to overall ECL emission, including selection of oxalate as a coreactant instead of TPA, or introduction of gold electrode as substrate. Furthermore, when Ru(bpy)32+ and AuNPs were both immobilized on the ITO electrode at close proximity, the ECL quenching induced by energy/electron transfer was predominant. ECL emission of the Ru(bpy)32+/TPA system resulted from a competition between electrocatalytic enhancement and quenching effect. However, the quenched ECL signal would return in case of the AuNPs moving far away from ECL emitters after a hybridization reaction as before, and a separation distance dependent surface enhancement was observed as well. Based on the role change for AuNPs from quenching to enhancing ECL intensity of Ru(bpy)32+/TPA system, a novel ECL DNA sensing strategy in a "turn-on" mode was developed, enabling quantitative analysis of target ssDNA over the range of 0.05 pM to 0.5 nM with a detection limit of 12 fM. Overall, we demonstrated the existence of three effects of AuNPs on the ECL of Ru(bpy)32+/TPA system, and which played the leading role was dependent on the placement of AuNPs, Ru(bpy)32+, and their separation distance. The ECL sensors based on the role change for AuNPs showed both high sensitivity and excellent selectivity.

P2X7 receptor in spinal tuberculosis: Gene polymorphisms and protein levels in Chinese Han population.

Spinal tuberculosis (TB) accounts for 1%-5% of all TB infections. Host genetic variation influences susceptibility to Mycobacterium tuberculosis (MTB). P2X7 receptor (P2X7R) expressed on cells has been identified as a regulatory molecule in cell death/apoptosis, killing of intercellular pathogens, and bone turnover. This study investigated the P2X7 gene polymorphisms and protein levels in spinal TB. P2X7 gene -762C>T and 489C>T polymorphisms were genotyped. The expression of P2X7R in bone or intervertebral disc (ID) tissues was analyzed by Western blot assay. The -762C>T and 489C>T polymorphisms were associated with susceptibility to spinal TB. Having the -762CC genotype and -762C allele increased the risk of developing spinal TB (CC vs. TT: P=0.031, OR [95%CI]=1.865 [1.053-3.304]; C vs. T: P=0.028, OR [95%CI]=1.355 [1.034-1.775]). The presence of the 489T allele was associated with an increased risk of developing spinal TB (TT vs. CC: P=0.004, OR [95%CI]=2.248 [1.283-3.939]; CT vs. CC: P=0.044, OR [95%CI]=1.755 [1.011-3.047]; T vs. C: P=0.004, OR [95%CI]=1.482 [1.134-1.936]; TT+CT vs. CC: P=0.010, OR [95%CI]=1.967 [1.171-3.304]; TT vs. CT+CC: P=0.037, OR [95%CI]=1.489 [1.023-2.167]). The expression of P2X7R in TB-induced bone lesions increased significantly among spinal TB patients (t=0.011). Carrying the P2X7 -762CC genotype and 489T allele is associated with an increased risk of developing spinal TB in a Southern Chinese Han population.

Label-free electrochemiluminescence assay for aqueous Hg2+ through oligonucleotide mediated assembly of gold nanoparticles.

Development of ultrasensitive method for Hg2+ analysis is important for human health protection and environment monitoring. In this work, we present a highly sensitive and selective electrochemiluminescence (ECL) assay in a "turn-on" mode for the detection of Hg2+ through selective assembly of gold nanoparticles (AuNPs) on the surface of indium tin oxide (ITO) electrode. In the absence of Hg2+, the nonthiolated ssDNA could protected AuNPs against its assembly on ITO surface, producing rather low ECL emission for Ru(bpy)32+/TPA system. Conversely, binding of Hg2+ with the Hg2+-specific oligonucleotide through thymine-Hg2+-thymine coordination formed the double-stranded structure, which could not effectively adsorb to AuNPs in solution. The assembly of free-state AuNPs is achieved, which well preserves electronical conductivity. The presence of AuNPs can catalyze the electro-oxidation of TPA, producing significantly enhanced ECL signal. Through detecting the ECL signal mediated by assembly of AuNPs, the proposed method was able to ensure substantial signal amplification and a low background. It was demonstrated that the ECL intensity was correlated with the ssDNA-based recognition reaction, enabling quantitative analysis of Hg2+ over the range of 8pM to 2nM, with a detection limit of 2pM. ECL intensity of the system were extremely specific for Hg2+ even in the presence of 1000-fold higher concentrations of other metal ions. Analytical results of Hg2+ spiked into water samples by the proposed ECL method were in good agreement with that obtained by atomic fluorescent spectrometry or mass spectrometry data.

Polymorphisms in the SP110 and TNF-α Gene and Susceptibility to Pulmonary and Spinal Tuberculosis among Southern Chinese Population.

OBJECTIVE: To investigate the association of single-nucleotide polymorphisms (SNPs) in SP110 gene and TNF-α gene among pulmonary TB (PTB) and spinal TB (STB) patients. METHODS: In a total of 190 PTB patients, 183 STB patients were enrolled as the case group and 362 healthy individuals at the same geographical region as the control group. The SP110 SNPs (rs722555 and rs1135791) and the promoter -308G>A (rs1800629) and -238G>A (rs361525) polymorphisms in TNF-α were genotyped. Results. TNF-α -238G>A polymorphism was involved in susceptibility to STB, but not to PTB. The TNF-α -238 A allele was a protective factor against STB (A versus G: OR [95% CI] = 0.331 [0.113-0.972], P = 0.044). Furthermore, the presence of the -238 A allele was considered a trend to decrease the risk of STB (AG versus GG: P = 0.062, OR [95% CI] = 0.352 [0.118-1.053]; AA + AG versus GG: P = 0.050, OR [95CI%] = 0.335 [0.113-0.999]). However, SP110 SNPs (rs722555 and rs1135791) and TNF-α -308G>A (rs1800629) showed no association with PTB and STB in all genetic models. CONCLUSION: The TNF-α -238 A allele appeared a protective effect against STB, whereas the SP110 SNPs (rs722555 and rs1135791) and TNF-α -308G>A (rs1800629) showed no association with susceptibility to PTB and STB patients in southern China.

Effect of BIX-01294 on H3K9me2 levels and the imprinted gene Snrpn in mouse embryonic fibroblast cells.

Histone H3 lysine 9 dimethylation (H3K9me2) hypermethylation is thought to be a major influential factor in cellular reprogramming, such as somatic cell nuclear transfer (SCNT) and induction of pluripotent stem cells (iPSCs). The diazepin-quinazolin-amine derivative (BIX-01294) specifically inhibits the activity of histone methyltransferase EHMT2 (euchromatic histone-lysine N-methyltransferase 2) and reduces H3K9me2 levels in cells. The imprinted gene small nuclear ribonucleoprotein N (Snrpn) is of particular interest because of its important biological functions. The objective of the present study was to investigate the effect of BIX-01294 on H3K9me2 levels and changes in Snrpn DNA methylation and histone H3K9me2 in mouse embryonic fibroblasts (MEFs). Results showed that 1.3 µM BIX-01294 markedly reduced global levels of H3K9me2 with almost no cellular toxicity. There was a significant decrease in H3K9me2 in promoter regions of the Snrpn gene after BIX-01294 treatment. A significant increase in methylation of the Snrpn differentially methylated region 1 (DMR1) and slightly decreased transcript levels of Snrpn were found in BIX-01294-treated MEFs. These results suggest that BIX-01294 may reduce global levels of H3K9me2 and affect epigenetic modifications of Snrpn in MEFs.

A facile and sensitive electrochemiluminescence biosensor for Hg2+ analysis based on a dual-function oligonucleotide probe.

In this study, a sensitive electrochemiluminescent (ECL) biosensor for the detection of Hg(2+) was easily prepared by self-assembling mercury-specific oligonucleotide on the surface of gold nanoparticles (AuNPs) modified indium tin oxide (ITO) electrode. A conformation change of the oligonucleotide from linear chain to hairpin occurs upon the binding of Hg(2+) through thymine-Hg(2+)-thymine coordination. The dual-function oligonucleotide serves as the probe to Hg(2+) but also a carrier of signal-generating molecules, [Ru(bpy)2(dppz)](BF4)2. It was estimated that one oligonucleotide was able to load with eight ECL signal molecules; a ratio of four or five oligonucleotides per gold nanoparticle was obtained basing on the calculation with surface density. Without tedious multiple-labeling procedures and special modification of oligonucleotide probe for signal transduction/amplification, a detection limit of 5.1 pM Hg(2+) was outstanding from the interference of other ten metal ions. Results of spiked water samples were in good agreement with that obtained by atomic fluorescent spectrometry.

Direct analysis of mercury in Traditional Chinese Medicines using thermolysis coupled with on-line atomic absorption spectrometry.

The purpose of this study is to develop and apply a mercury analyzer system capable of quantitative analysis of mercury in Traditional Chinese Medicines (TCM) drugs in the concentrations range from ng g(-1) to mg g(-1). No sample pre-treatment was needed and this greatly simplifies the analytical procedure and minimizes potential sources of contamination. The precisions of analyzing solid mercury standard sample and real TCM materials were 2.1% and 2.5-8.2%, respectively; and the recovery based on the analysis of standard reference materials ranged from 95.2% to 105%. The performance of the method has been compared with inductively coupled plasma-mass spectrometry (ICP-MS) technique and excellent agreements were observed between the two methods. The method has been applied to the investigation of Hg content in several TCM drugs containing or not containing cinnabar. Mercury concentration in the same TCM products differs widely with different manufacturers, suggesting that external contamination and the Hg presence in raw herbal materials are the main sources of Hg. In addition, comparison of mercury thermal releasing profiles between TCM drug and cinnabar suggests that mercury conversion from cinnabar to biological matrices-bound Hg could occur because of the aid of other ingredients in the formulated drug.