ABSTRACT
Objective: The purpose of our study was to investigate the clinical characteristics, molecular biological characteristics and prognosis of acute myeloid leukemia (AML) patients with protein tyrosine phosphatase non-receptor type 11 (PTPN11) gene mutation. Methods: The clinical data of 30 newly diagnosed adult AML patients with PTPN11 gene mutation were analyzed retrospectively. Kaplan-Meier and Cox proportional risk regression model were examined for prognostic analysis and prognostic factor screening. Results: High-frequency mutation sites of PTPN11 gene are located in exon 3 of chromosome 12, which are D61 and A72 (16.7%), followed by E76 (13.3%). The median variant allele frequency (VAF) of PTPN11 mutant gene is 18.4%. The patients were divided into two groups according to PTPN11 VAF 35.3% (upper quartile). We observed that the peripheral blood leukocyte count in patients with VAF ≥35.3% was significantly higher than patients with VAF < 35.3% (p = 0.019) and also closely related to M5 (p = 0.016) and internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3) (FLT3-ITD) mutation (p = 0.048). Taking PTPN11 VAF 20% and 35.3% as the cutoff value, the patients were divided into two groups, and the overall survival and event-free survival (EFS) of the two groups were not significant. Multivariate analysis of Cox risk ratio model showed that white blood cell count and Eastern Cooperative Oncology Group (ECOG) physical status score were independent risk factors affecting the EFS. Conclusion: Our study observed that PTPN11 VAF may not be a prognostic factor in patients with PTPN11mut AML. Newly diagnosed high white blood cell count and poor performance status were independent risk factors for EFS in PTPN11mut AML.
ABSTRACT
Hodgkin lymphoma (HL)-related hemophagocytic lymphohistiocytosis (HLH) has been reported in the literature; however, there is almost no literature on the factors related to HL triggering HLH. One hundred forty patients with HL were retrospectively analyzed. The incidence of HL-related HLH (we call HL-related HLH as HL-HLH). And all HL-HLH patients in our cohort had HLH as the first manifestation and its clinical characteristics and the role of intrathoracic infection (ITI) in triggering HLH are discussed. The 140 patients with HL mainly included mixed-cellularity classic HL (MCCHL) in 81 (57.9%), nodular sclerosis classic HL (NSCHL) in 36 (25.7%), and lymphacyte-rich classic HL in 14 (10.0%) patients. Of the 137 patients who underwent chest computed tomography scans on admission, 44 had ITI, and most of these ITI were mildly ill and had no respiratory symptoms. Among 140 HL patients, 8 patients from MCCHL were diagnosed as HL-HLH. Among 81 MCCHL patients, 26 patients with ITI had a significantly higher incidence of HL-HLH than those without ITI (26.9% vs 1.8%, P = .002). The median survival time of 8 cases of HL-HLH was only 2 months. When HL patients were first admitted to the hospital, 5.7% had HLH as the first manifestation, and 32.1% had ITI. These ITI can cooperate with HL to trigger HLH, despite their mild illness. The prognosis of HL-HLH was poor.
Subject(s)
Hodgkin Disease , Lymphohistiocytosis, Hemophagocytic , Hodgkin Disease/complications , Hodgkin Disease/epidemiology , Hospitalization , Hospitals , Humans , Lymphohistiocytosis, Hemophagocytic/epidemiology , Retrospective StudiesABSTRACT
OBJECTIVE: To investigate the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11 (FLT3-ITD+). METHODS: MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot. RESULTS: Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group (P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group (P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs (P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group (P<0.001); increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3ãp-STAT5 protein in the combination group was significantly lower than that in the single drug group (P<0.05, P<0.05). CONCLUSION: Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.
Subject(s)
Leukemia, Myeloid, Acute , STAT5 Transcription Factor , Apoptosis , Benzothiazoles , Cell Line, Tumor , Humans , Leukemia, Myeloid, Acute/genetics , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Phenylurea Compounds , RNA, Messenger , STAT5 Transcription Factor/genetics , STAT5 Transcription Factor/metabolism , STAT5 Transcription Factor/pharmacology , Signal Transduction , fms-Like Tyrosine Kinase 3ABSTRACT
To accurately determine neonicotinoid pesticide residues in goji berries, porous boron nitride nanorods (p-BNNRs) were prepared and used as a new QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) clean-up sorbent. Combined with ultrahigh-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), a modified QuEChERS method was developed to determine five neonicotinoid pesticide residues in goji berries. In goji berries, the p-BNNRs were shown to have a greater clean-up ability than typical clean-up materials (C18, PSA) The recoveries of the five targets ranged from 78.1 to 117.3% at three fortified levels, and the LODs ranged from 2.2 to 3.7 µg kg-1. The results indicate that this approach could be successfully used to quickly determine of the five neonicotinoid insecticide residues in goji berries for risk assessment purposes, demonstrating the applicability and suitability of p-BNNRs for the routine evaluation of neonicotinoid insecticide residues in goji berries.
Subject(s)
Insecticides , Lycium , Nanotubes , Pesticide Residues , Boron Compounds , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid/methods , Insecticides/analysis , Neonicotinoids/analysis , Pesticide Residues/analysis , Porosity , Tandem Mass Spectrometry/methodsABSTRACT
Wolfberry fruit has been attracting attention for centuries in Asian countries as a traditional herbal medicine and valuable nourishing tonic. Revealing the spatial distribution changes of important endogenous molecules during plant development is of great significance for investigating the physiological roles, nutritional and potential functional values of phytochemicals in wolfberry fruit. However, their spatial distribution information during fruit development has not been extensively explored due to the lack of efficient analytical techniques. In this work, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was performed to visualize the spatial distribution of the endogenous molecules during fruit development. From the mass spectrum imaging, the choline, betaine and citric acid were distributed evenly throughout the entire fruit at all development stages. The hexose was distributed in the endocarp and flesh tissue, while sucrose was located in the seeds. Additionally, several phenolic acids and flavonoids were accumulated in the exocarp during fruit development, which indicated that they seemingly played protective roles in wolfberry fruit growth progress against abiotic and biotic stress. From the collected data, we found that the signal intensities of citric acid were decreased, while choline, betaine, hexose and sucrose were increased with fruit development. These results indicate that MALDI-MSI may become a favorable tool for studying of the spatial distribution and effective use of endogenous molecules, which provide a simple and intuitive way for authenticity identification, classification of drug food homologous foods and further understanding the physiological roles of endogenous molecules.
Subject(s)
Fruit , Lycium , Flavonoids , Lasers , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Making full use of the undeveloped bioactive natural product derivatives by selectively delivering them to target sites can effectively increase their druggability and reduce the wastage of resources. Azo-based prodrugs are widely regarded as an effective targeted delivery means for colon-related disease treatment. Herein, we report a new-type of azo-based nanoprodrug obtained from bioactive natural products, in which the readily available podophyllotoxin natural products are connected with methoxy polyethylene glycol (mPEG) via a multifunctional azobenzene group. The amphiphilic prodrug can form nanosized micelles in water and will be highly selectively activated by azoreductases, leading to the in situ generation of anticancer podophyllotoxin derivatives (AdP) in the colon after the cleavage of the azo bond. To satisfy the demand of drug carriers for cancer combination therapy in clinics, α-CD is further introduced into this nanoprodrug micelle system to form a supramolecular hydrogel via a cascade self-assembly strategy. Using imaging mass spectrometry (IMS), the colon-specific drug release ability of the hydrogel after oral administration is demonstrated at the molecular level. Finally, the nanoprodrug hydrogel is further used as a carrier to load a hydrophilic anti-cancer drug 5-FU during the hierarchical self-assembly process and to co-deliver AdP and 5-FU for the drug combination. The combination use of AdP and 5-FU provides enhanced cytotoxicity which indicates a significant synergistic interaction. This work offers a new way to enhance the therapeutic effect of nanoprodrugs via drug combination, and provides a new strategy for reusing bioactive natural products and their derivatives.
Subject(s)
Antineoplastic Agents/pharmacology , Hydrogels/chemistry , Nanoparticles/chemistry , Podophyllotoxin/pharmacology , Prodrugs/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Chlorocebus aethiops , Drug Carriers/chemical synthesis , Drug Carriers/chemistry , Drug Screening Assays, Antitumor , Hep G2 Cells , Humans , Hydrogels/chemical synthesis , Micelles , Molecular Structure , Particle Size , Podophyllotoxin/chemistry , Prodrugs/chemical synthesis , Prodrugs/chemistry , Vero CellsABSTRACT
In the present study, nine compounds (1-9) were isolated from Talaromyces wortmannii LGT-4 (an endophytic fungus from Tripterygium wilfordi) which was cultured in CYM Medium. Their structures were determined as 4-hydroxyphthalide (1), Fumitremorgin C (2), Ergosterol (3), 3-(2-hydroxypropyl)-8-hydroxy-3,4- dihydroisocoumarin (4), Cis-cyclo(L-Ala-L-Pro) (5), 6-Amino-3-(4-hydroxybenzyl)- 1,4-diazonane-2,5-dione (6), Aspergillumarin B (7), Deacetylisowortmin B (8), and Entonaemin A (9) based on NMR spectral data, as well as comparing with previous literature data. This is the first report of the isolation of compounds 1-2 and 4-7 from Talaromyces genus. All compounds were tested for their monoamine oxidase and phosphoinositide 3-kinase (PI3Kα) inhibitory activities. Compound 1, 5 showed moderate anti-monoamine oxidase activity with IC50 value of 35 µg/mL, 28 µg/mL, respectively. Compound 9 showed PI3Kα inhibitory activity with IC50 value of 10.3 µg/mL.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a novel type of highly contagious pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the strong efforts taken to control the epidemic, hundreds of thousands of people were infected worldwide by 11 March, and the situation was characterized as a pandemic by the World Health Organization. Pregnant women are more susceptible to viral infection due to immune and anatomic alteration, though hospital visits may increase the chance of infection, the lack of medical care during pregnancy may do more harm. Hence, a well-managed system that allows pregnant women to access maternal health care with minimum exposure risk is desired during the outbreak. Here, we present the managing processes of three pregnant women who had fever during hospitalization in the gynecology or obstetrics department, and then, we further summarize and demonstrate our maternal health care management strategies including antenatal care planning, patient triage based on the risk level, admission control, and measures counteracting emergencies and newly discovered high-risk cases at in-patient department. In the meantime, we will explain the alterations we have done throughout different stages of the epidemic and also review relative articles in both Chinese and English to compare our strategies with those of other areas. Although tens of COVID-19 cases were confirmed in our hospital, no nosocomial infection has occurred and none of the pregnant women registered in our hospital was reported to be infected.
Subject(s)
Betacoronavirus/pathogenicity , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Disease Outbreaks , Fever/diagnosis , Health Services Accessibility/organization & administration , Pneumonia, Viral/diagnosis , Pregnancy, Ectopic/diagnosis , Adult , Betacoronavirus/genetics , Biomarkers/blood , COVID-19 , COVID-19 Testing , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Diagnosis, Differential , Female , Fever/blood , Fever/epidemiology , Fever/virology , Hospitalization/statistics & numerical data , Humans , Maternal Health , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Pregnancy , Pregnancy, Ectopic/blood , Pregnancy, Ectopic/epidemiology , Pregnancy, Ectopic/virology , SARS-CoV-2 , Tomography, X-Ray Computed , Triage/organization & administrationABSTRACT
Non-Hodgkin lymphoma (NHL) can co-exist with autoimmune hemolytic anemia (AIHA), a phenomenon known as AIHA-associated NHL (AIHA/NHL). However, few studies have reported AIHA/NHL incidence or its clinical characteristics. We conducted a retrospective analysis of 20 AIHA/NHL patients treated at our hospital from 2009 to 2018. AIHA/NHL was presented by only 0.91% of the NHL and 9.8% of the AIHA patients. In addition, AIHA occurred most frequently with angioimmunoblastic T-cell lymphoma (AITL) (7.31%), followed by marginal zone B-cell lymphoma (MZBL) (6.25%), B-cell lymphoma-unclassified (BCL-U) (4.25%), chronic lymphocytic leukemia/small lymphocyte lymphoma (CLL/SLL) (2.50%), and mantle cell lymphoma (MCL) (2.30%). In addition to the CLL/SLL patients with impaired bone marrow, 66.7% of the AIHA/NHL patients had lymphoma bone marrow infiltration (LBMI), of which 4 patients presented LBMI in bone marrow smears (BMS) but not in bone marrow biopsy (BMB) and 6 were positive for BMB but not BMS. The 1-, 3- and 5-year survival rates of AIHA/NHL patients were 70%, 30% and 20%, respectively, and they responded poorly to chemotherapy. In conclusion, AIHA can co-exist with various NHLs and the defining clinical characteristic of AIHA/NHL is the high incidence of LBMI. However, both BMS and BMB should be performed to avoid missed diagnosis.
Subject(s)
Anemia, Hemolytic, Autoimmune/epidemiology , Bone Marrow/pathology , Lymphoma, Non-Hodgkin/epidemiology , Adult , Aged , Aged, 80 and over , Anemia, Hemolytic, Autoimmune/pathology , Biopsy , Female , Humans , Incidence , Lymphoma, Non-Hodgkin/classification , Lymphoma, Non-Hodgkin/pathology , Male , Middle Aged , Retrospective Studies , Survival AnalysisABSTRACT
BACKGROUND: Bortezomib is a first-line drug approved for patients with multiple myeloma (MM) and has significantly increased their overall survival. However, bortezomib-induced peripheral neuropathy (PN) remains a significant side effect that has led to its discontinuation in some patients. Guillain-Barré syndrome (GBS) is recognized as an immune-mediated PN characterized by the involvement of multiple nerve roots and peripheral nerves and albuminocytologic dissociation in cerebrospinal fluid (CSF) tests. Intravenous immunoglobulin (IVIG) and plasmapheresis are effective. CASE SUMMARY: A 45-year-old man diagnosed with stage III MM (λ type) was treated with bortezomib and dexamethasone. Fourteen days after the second course, he complained of intense burning sensation in the lower limbs and hands, loss of tactile sensation, and pain in the distal area of both thighs and in the distal part of both wrist joints. Neurological examination revealed absence of knee and ankle reflexes. CSF examination revealed albuminocytologic dissociation. Nerve conduction studies indicated sensory nerve action potential amplitudes, conduction velocity decrease, and F wave latency prolongation. He was diagnosed as MM complicated with GBS. Subsequently, he was treated with high-dose IVIG (400 mg/kg/d for five days). His symptoms fully resolved without relapse at the 6-month follow-up. CONCLUSION: Our case highlights the differential diagnosis and management of complications after bortezomib treatment in MM.
ABSTRACT
BACKGROUND: Hox transcript antisense intergenic RNA (HOTAIR) is upregulated and associated with a poor prognosis in many cancer types. Besides, it is involved in the invasion and metastasis of non-small-cell lung cancer and nasopharyngeal carcinoma. OBJECTIVES: The aim of this study was to investigate the association between the expression of HOTAIR and the grades of gliomas, and to explore its possible mechanism, as well as to evaluate the value of HOTAIR applied in predicting the grades of gliomas. MATERIAL AND METHODS: A total of 123 patients undergoing glioma surgeries were enrolled. Patients with grade I and grade II-IV tumors were regarded as the control group (n = 36) and the case group (n = 87), respectively. The expression of HOTAIR, matrix metalloproteinase 7 (MMP-7), matrix metalloproteinase 9 (MMP-9), and vascular endothelial growth factor (VEGF) was detected with quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in glioma tissues and then compared between grade I and grades II-IV. The correlation between the relative expression of HOTAIR and that of MMP-7, MMP-9 and VEGF was analyzed. Multivariate analysis was performed to identify independent risk factors. Receiver operating characteristic (ROC) curve was employed to evaluate the predictive value. RESULTS: The relative expression of HOTAIR, MMP-7, MMP-9, and VEGF was lower in glioma tissues of grade I than in the case of grades II-IV, and the relative expression of HOTAIR was positively correlated with the relative expression of MMP-7, MMP-9 and VEGF. Multivariate analysis showed that the relative expression of HOTAIR was independently associated with the grades of gliomas, but the relative expression of MMP-7, MMP-9 and VEGF was not. Besides, multivariate analysis showed that the expression level of HOTAIR >0.40 was an independent risk factor for grades II-IV after classifying the relative expression of HOTAIR, and ROC analysis showed that the expression level of HOTAIR >0.40 had a moderate value when applied in predicting grades II-IV. CONCLUSIONS: Hox transcript antisense intergenic RNA might promote the invasion of gliomas through upregulating the expression of MMP-7, MMP-9 and VEGF, and the expression level of HOTAIR >0.40 had a moderate value when applied in predicting grades II-IV.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Glioma , Lung Neoplasms , RNA, Long Noncoding/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Gene Expression Regulation, Neoplastic , Glioma/genetics , Glioma/pathology , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Neoplasm Grading , Neoplasm Staging , Prognosis , Vascular Endothelial Growth Factor AABSTRACT
OBJECTIVE: To detect the expression of miR-99a-5p in myelodysplastic syndrome (MDS), to predict the target genes and to analyze its function by using bioinformatics. METHODS: The expression levels of bone marrow miR-99a-5p in MDS patients were detected by qRT-PCR, and the correlation of miR-99a-5p expression with clinical pathological characteristics, percentage of marrow blasts , chromosome karyotype and peripheral blood hemogram were analyzed. The target genes of miR-99a-5p were predicted by Targetscan, Miranda and Microcosm, and the intersection of the predicted results of 3 softwares was used as a potential target gene for miR-99a-5p. RESULTS: The expression level of bone marrow miR-99a-5p in MDS patients was significantly higher than that of healthy controls (P<0.01); According to the prognostic score of IPSS, MDS patients were divided into relatively low risk group (including low risk group and intermediate risk group 1) and relatively high risk group (including intermediate risk group 2 and high risk group). Analysis showed that the expression level of bone marrow miR-99a-5p in relatively low risk group was 2.40 times higher than that in healthy control group (P<0.01), the expression level of bone marrow miR-99a-5p in relatively high risk group was 6.66 times higher than that in healthy control group (P<0.01), the expression level of miR-99a-5p in relatively high risk group was 2.80 times higher than that in the relatively low risk group ( P<0.01) ; the expression level of bone marrow miR-99a-5p in t-MDS group was 6.35 times higher than that in healthy control group (P<0.001). There was a significant positive correlation between the expression level of miR-99a-5p and the percentage of marrow blasts (P<0.01), but the expression of miR-99a-5p did not correlate with chromosome karyotype and peripheral blood hemogram; In this study it was obtained that ST5 might participate in pathological mechanism of MDS by bioinformatic analyses and references. CONCLUSION: The expression levels of miR-99a-5p is up-regulated in MDS patients, and its expression showed a rising tendency which may be involved in the pathogenesis of MDS by regulating target gene ST5.
Subject(s)
Myelodysplastic Syndromes , Bone Marrow , Computational Biology , Humans , Karyotyping , MicroRNAsABSTRACT
DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo. Finally, we demonstrated that DEPDC1 interacted with E2F1 and increased its transcriptional activity, leading to hyper-activation of E2F signaling in prostate cancer cells. Our findings reveal an oncogenic role of DEPDC1 in prostate cancer progression via activation of E2F signaling, and suggest DEPDC1 might be a potential therapeutic target against the disease.
Subject(s)
E2F Transcription Factors/metabolism , GTPase-Activating Proteins/metabolism , Neoplasm Proteins/metabolism , Prostate/pathology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Signal Transduction , Animals , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Bone and Bones/metabolism , Bone and Bones/pathology , Cell Cycle , Cell Line, Tumor , Cell Proliferation , GTPase-Activating Proteins/genetics , Gene Expression Regulation, Neoplastic , Humans , Male , Mice, Inbred BALB C , Neoplasm Proteins/genetics , Prostate/metabolism , Prostatic Neoplasms/genetics , Up-RegulationABSTRACT
OBJECTIVE: To study the clinical implications of death-associated protein kinase (DAPK) promoter methylation and DAPK gene expression in untreated patients with acute leukemia. METHODS: Methylation-specific PCR and RT-PCR were employed to detect the DAPK gene methylation and mRNA expression in the bone marrow of 60 patients with acute myeloid leukemia (AML), 55 patients with acute lymphocytic leukemia (ALL), and 17 normal subjects. RESULTS: The positivity rate of DAPK methylation was significantly higher in ALL patients (29.1%) than in AML patients group (5%) and normal subjects (0%) (P<0.01). No correlation was found between DAPK gene methylation and the clinical features in ALL patients (P>0.05). DAPK mRNA expression level differed significantly among the 3 groups (P=0.000), and was the highest in normal subjects and the lowest in ALL patients. In ALL patients, the expression level of DAPK mRNA showed a significant inverse correlation with DAPK promoter methylation (P<0.05). CONCLUSION: The methylation rate of DAPK gene is higher in untreated ALL patients than in AML patients and normal subjects. DAPK gene methylation is not correlated with the clinical features of ALL patients but is probably related with the low gene expression level of DAPK in these patients.
Subject(s)
DNA Methylation , Death-Associated Protein Kinases/metabolism , Leukemia, Myeloid, Acute/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Promoter Regions, Genetic , Case-Control Studies , Death-Associated Protein Kinases/genetics , Humans , Leukemia, Myeloid, Acute/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/geneticsABSTRACT
OBJECTIVE: To investigate the expression of miR-550a-5p in bone marrow of patients with myelodysplastic syndrome (MDS), and to predict its target genes and function by bioinformatics analyses, so as to provide the evidence to furthre explore the role of miR-550a-5p and its target genes in pathogenesis of MDS. METHODS: Real-time PCR was used to detect the expression of miR-550a-5p in 54 MDS patients, 16 acute myeloid leukemia transformed from MDS (sfAML) and 19 healthy controls, and the correlation between the expression of miR-550a-5p and clinical pathologic characteristics of MDS, including chromosome, percentage of marrow blasts, absolute neutrophil count, platelet count and hemoglobin levels were analyzed. The sequence of miR-550 was searched in miRBase database. Target genes of miR-550a-5p were predicted by Microcosm,Miranda and Targetscan, and the predective results were collected, then the enrichment analyses of target gene function(GO) and signalling pathway(pathway of miR-550a-5p) were carried out by using gene ontology darabase and KEGG database. RESULTS: The expression of miR-550a-5p in bone marrow of all MDS patients was higher than that in controls: the expression level of miR-550a-5p in low risk MDS and middl risk 1 MDS was 1.7 times of controls (P=1.23×10-10); the expression of miR-550a-5p in midde risk 2 MDS and high risk MDS was 1.9 times of controls (P=1.20×10-10); the expression of miR-550a-5p in tAML was 2.0 times of controls (P=5.61×10-10). The miR-550a-5p expression level was up-regulated gradually with the enhancement of disease risk of MDS, but there was no correlation between the expression level of miR-550a-5p and clinical pathologic characteristics of MDS(chromosome: Normal: 1.11±0.19, Abnormal:1.26±0.15, P>0.05; Percentage of Marrow Blasts: r=0.29,P=0.07; absolute neutrophil count: r=-0.02,P=0.89; hemoglobin level: r=0.09,P=0.57; platelet count: r=0.25,P=0.08). The sequence of miR-550 was conservative among different species, and the prediced results indicated that there were 19 target genes in intersection. The functions of target genes were enriched in regulation of stress-activated cascade, MAPK pathway, regulation of muscle organ development, regulation of protein homodimerization activity and other biological processes; they participated in some molecular functions including enzyme activity, combination processes of some molecules as protein, cAMP and domain existed in cell junction, synapse, coated vesicle, dendrite and other cellular components. Two of them-PDLIM2 and PSME1 were selected which might play a role in pathologic mechanism of MDS regulated by miR-550a-5p. CONCLUSION: The expression of miR-550a-5p in bone marrow of MDS patients increases specifically, and miR-550a-5p may play a role in the pathogenesis of MDS through regulation of target genes, PDLIM2 and PSME1.
Subject(s)
Myelodysplastic Syndromes , Bone Marrow , Computational Biology , Humans , Leukemia, Myeloid, Acute , MicroRNAs , Real-Time Polymerase Chain Reaction , Up-RegulationABSTRACT
OBJECTIVE: To explore the effect of DAPK overexpression on the biological behaviors and caspase-3 expression in HL-60 cells. METHODS: The expression of DAPK mRNA was detected by RT-PCR leukemia cell lines K562, Molt4, U937, and HL-60 cells. HL-60 cells were transfected by a eukaryotic expression vector pReceiver-M29-DAPK via LipofectamineTM 2000, and the impact of DAPK overexpression on cell apoptosis, cell cycle, cell differentiation and caspase-3 expression were analyzed. RESULTS: DAPK mRNA expression was positive in K562, Molt4 and U937 cells but negative in HL-60 cells. Significantly increased cell apoptosis was observed in pReceiver-M29-DAPK-transfected HL-60 cells by flow cytometry and Hoechst33342 staining. The cell cycle distribution and differentiation showed no significant changes after the transfection. The expression of caspase-3 was significantly increased in the cells after transfection. CONCLUSION: DAPK gene overexpression promotes apoptosis of HL-60 cells without affecting the cell cycle and differentiation. Caspase-3 may be involved in the regulation of cell apoptosis.
Subject(s)
Apoptosis , Caspase 3/metabolism , Cell Cycle , Death-Associated Protein Kinases/metabolism , Cell Differentiation , Cell Line, Tumor , HL-60 Cells , Humans , RNA, Messenger/metabolism , Transfection , U937 CellsABSTRACT
OBJECTIVE: To review the literature and assess the comparative effectiveness of ultrasound-guided (USG) versus computed tomography (CT)-/fluoroscopy-guided lumbar facet joint injections in adults. DATA SOURCES: PubMed, Ovid MEDLINE, Ovid Embase, EBSCO, and Web of Science. STUDY SELECTION: Randomized or nonrandomized controlled trials comparing the clinical effectiveness between USG and CT-/fluoroscopy-guided injection techniques in patients with facet syndrome were included. DATA EXTRACTION: Two reviewers independently screened abstracts and full texts. The results of the mean procedure duration, decreased pain score, and Modified Oswestry Disability score after treatment were extracted and presented in the form of mean ± SD. DATA SYNTHESIS: There were 103 records screened; 3 studies were included, with a total of 202 adults with facet joint pain. There was no statistically significant difference between the 2 groups in pain score and Modified Oswestry Disability score after injection (weighted mean difference [WMD], .07; 95% confidence interval [CI], -.51 to .65; P=.80; I(2)=78%; WMD, -.55; 95% CI, -1.31 to .22; P=.16; I(2)=0%, respectively). There was also no statistically significant difference in the mean procedure duration between the 2 groups (standardized mean difference [SMD], .97; 95% CI, -1.01 to 2.94; P=.34; I(2)=97%). CONCLUSIONS: This review suggested that no significant differences in pain and functional improvement were noted between the USG and CT-/fluoroscopy-guided techniques in facet joint injection. USG injection is feasible and minimizes exposure of radiation to patients and practitioners in the lumbar facet joint injection process.
Subject(s)
Injections, Intra-Articular/methods , Low Back Pain/drug therapy , Lumbar Vertebrae/diagnostic imaging , Zygapophyseal Joint/diagnostic imaging , Fluoroscopy , Humans , Radiography, Interventional/methods , Tomography, X-Ray Computed , Ultrasonography, Interventional/methodsABSTRACT
OBJECTIVE: The study aimed to validate the efficacy of detection of fetal cell-free DNA in maternal plasma of trisomy 21, 18 and 13 in a clinical setting. METHODS: A total of 2340 women at high risk for Down syndrome based on maternal age, prenatal history or a positive sesum or sonographic screening test were offered prenatal noninvasive aneuploidy test. According to the prenatal noninvasive aneuploidy test, the pregnant women at high risk were offered amniocentesis karyotype analysis and the pregnant at low risk were followed up to make sure the newborn outcome. RESULTS: The prenatal noninvasive aneuploidy test was positive for trisomy 21 in 17 cases, for trisomy 18 in 6 cases and for trisomy 13 in 1 case, which of all were confirmed by karyotype analysis. Newborns of low risk gestational woman detected by prenatal noninvasive aneuploidy for trisomy 21, 18, 13 were followed up and no one was found with trisomy. CONCLUSIONS: The prenatal noninvasive aneuploidy test is highly accurate for detection of trisomy 21, 18 and 13, which can be considered as a practical alternative for traditional invasive diagnostic procedures.
Subject(s)
Interleukin-33/metabolism , Intra-Abdominal Fat/cytology , Receptors, Interleukin/metabolism , Signal Transduction , T-Lymphocytes, Regulatory/immunology , Animals , Humans , Interleukin-1 Receptor-Like 1 Protein , Lymphocyte Subsets/immunology , Mice, Inbred C57BL , Models, Biological , PhenotypeABSTRACT
Metallo-ß-lactamases (MBLs) can hydrolyze almost all ß-lactam antibiotics and are resistant to clinically available ß-lactamase inhibitors. Numerous types of acquired MBLs have been identified, including IMP, VIM, NDM, SPM, GIM, SIM, DIM, KHM, TMB, FIM and AIM. IMPs and VIMs are the most frequent MBLs and disseminate in members of the family Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp. Acquired MBL genes are often embedded in integrons, and some are associated with insertion sequence (IS) elements. The class 1 integrons and IS common region (ISCR) elements are usually harbored in transposons and/or plasmids, forming so-called mobile vesicles for horizontal transfer of captured genes between bacteria. Here, we review the MBL superfamily identified in Gram-negative bacteria, with an emphasis on the phylogeny of acquired MBLs and their genetic association with class 1 integrons and IS common region elements.