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1.
Obes Facts ; 17(1): 47-58, 2024.
Article in English | MEDLINE | ID: mdl-37935140

ABSTRACT

INTRODUCTION: It is controversial whether obesity and periodontitis are related. A representative US population was examined for the relationship between obesity and periodontitis. METHODS: In the National Health and Nutrition Examination Survey (NHANES) 2011-2014, participants (n = 6,662) aged 30 years or older and who underwent periodontal examinations were chosen for analysis. An assessment of obesity was based on body mass index (BMI) and waist circumference (WC). Estimates of obesity and periodontal disease were made using univariate and multivariate logistic regression models. RESULTS: According to an adjusted odds ratio (OR) for periodontitis, BMI (OR = 1.01, 95% CI: 1.01∼1.02) and WC (OR = 1.01, 95% CI: 1∼1.01) were significantly associated with periodontitis, respectively. After adjusting for confounding factors, the OR for patients with high WC with periodontitis was 1.18 (1.04∼1.33) compared to normal WC. BMI and WC subgroups showed no significant interaction (p for interaction >0.05), except for the age interaction in BMI. Among young adults aged 30-44 years, obesity was significantly associated with periodontitis in subgroups; the adjusted OR for having periodontal disease was 1.02 (1∼1.03) and 1.01 (1∼1.02) for subjects with BMI and WC, respectively. When all covariates were adjusted, BMI ≥30 kg/m2 was statistically significantly associated with prevalence of periodontal disease among people aged 30-44 years (p < 0.001). CONCLUSIONS: BMI and WC are significantly associated with periodontitis, even after adjusting for many variables, and were equally significant in obese (BMI ≥30 kg/m2) young people (30-44 years).


Subject(s)
Periodontal Diseases , Periodontitis , Young Adult , Humans , Adolescent , Nutrition Surveys , Obesity/complications , Obesity/epidemiology , Body Mass Index , Periodontitis/complications , Periodontitis/epidemiology , Waist Circumference , Risk Factors
2.
Front Public Health ; 10: 1073893, 2022.
Article in English | MEDLINE | ID: mdl-36684903

ABSTRACT

Congenital syphilis is a significant public health problem. Pregnant women infected with Treponema pallidum present with various clinical manifestations, mainly including skin or visceral manifestations. The extensive clinical manifestations of T. pallidum infection mimic those of many other diseases during pregnancy, which may lead to delayed diagnosis and serious consequences. We report a case of fetal T. pallidum infection and premature delivery in a woman whose syphilis screening was negative at 16 weeks of gestation. Despite presenting to the dermatologist at 24 weeks of gestation with maculopapular rash which is usually associated with secondary syphilis, the diagnosis of syphilis was not considered. This case shows that even if early syphilis screening of pregnant women is negative, they may still get infected with T. pallidum later on in pregnancy. Therefore, in patients presenting with a rash without an obvious cause, T. pallidum infection should be excluded. The health status of patients' spouses should be assessed during pregnancy. Additionally, perinatal health education is necessary for women and their spouses during pregnancy. The abovementioned factors could reduce the probability of T. pallidum infection in pregnant women and their infants.


Subject(s)
Exanthema , Pregnancy Complications, Infectious , Syphilis, Congenital , Syphilis , Infant , Female , Humans , Pregnancy , Syphilis, Congenital/diagnosis , Syphilis, Congenital/prevention & control , Pregnancy Complications, Infectious/diagnosis , Syphilis/diagnosis , Treponema pallidum
4.
Transl Oncol ; 14(7): 101088, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33882369

ABSTRACT

BACKGROUND: The lncRNA colorectal neoplasia differentially expressed (lncRNA CRNDE) has been reported to play a pivotal role in various cancers. However, the expression and function of CRNDE in pancreatic cancer remain unclear. The objective of this study was to investigate the effects of CRNDE on pancreatic cancer and the underlying mechanisms. METHODS: The expression of CRNDE in pancreatic cancer tissues and cell lines was determined by RT-qPCR. Proliferation and angiogenesis were detected by MTT, colony formation, transwell and tube formation assays in vitro and in vivo. ELISA assay was used to detect the secretion of VEGFA. IHC was performed to test the expression levels of Ki67 and CD31. The binding sites between CRNDE, CDKN2D and miR-451a were predicted by bioinformatics analysis. Dual luciferase reporter and RNA immunoprecipitation assays were conducted to confirm the interaction with each other. RESULTS: The results showed that CRNDE was significantly up-regulated in pancreatic cancer tissues as well as cell lines. CRNDE overexpression promoted the progression and angiogenesis of pancreatic cancer cells in vitro and in vivo. Moreover, we identified that CRNDE functioned as a sponge for miR-451a and CRNDE overexpression inhibited the expression of miR-451a. Furthermore, we confirmed that miR-451a directly interacted with CDKN2D and negatively regulated CDKN2D expression. In addition, CRNDE was found to positively regulate CDKN2D expression and mediate pancreatic cancer cell proliferation and angiogenesis through miR-451a/CDKN2D axis. CONCLUSION: CRNDE modulates cell proliferation and angiogenesis via miR-451a/CDKN2D axis in pancreatic cancer, which provides a potential therapeutic target for pancreatic cancer treatment.

5.
J Integr Neurosci ; 20(1): 55-65, 2021 Mar 30.
Article in English | MEDLINE | ID: mdl-33834691

ABSTRACT

Synaptic dysfunction and neuronal loss are related to cognitive impairment of Alzheimer's disease. Recent evidence indicates that regulating the phosphatidylinositol 3-Kinase (PI3K)/AKT/GSK-3ß pathway is a therapeutic strategy for improving synaptic plasticity in Alzheimer's disease. Here, we investigated "olfactory three-needle" effects on synaptic function and the PI3K/AKT/GSK-3ß signaling pathway in ß-amyloid1-42 (Aß1-42)-induced Alzheimer's disease rats. A three-needle olfactory bulb insertion for 28 days alleviated Aß1-42-induced Alzheimer's disease rats' cognitive impairment as assessed by performance in the Morris water maze test. Furthermore, the three-needle electrode inhibited neuro-apoptosis and neuro-inflammation. It significantly upregulated the protein expression of postsynaptic density protein 95, synaptophysin, and GAP43, indicating a protective effect on hippocampal synaptic plasticity. Additionally, the activation level of PI3K/AKT signaling and the phosphorylation inactivation of GSK-3ß were significantly enhanced by the "olfactory three-needle". Our findings suggested that the three-needle acupuncture is a potential alternative to improve synaptic plasticity and neuronal survival of Alzheimer's disease brain in rodents.


Subject(s)
Acupuncture Therapy , Alzheimer Disease/therapy , Apoptosis/physiology , Cognitive Dysfunction/therapy , Inflammation/therapy , Neuronal Plasticity/physiology , Olfactory Bulb , Signal Transduction/physiology , Alzheimer Disease/chemically induced , Alzheimer Disease/complications , Amyloid beta-Peptides/pharmacology , Animals , Behavior, Animal/physiology , Cognitive Dysfunction/etiology , Glycogen Synthase Kinase 3 beta/metabolism , Male , Maze Learning/physiology , Oncogene Protein v-akt/metabolism , Peptide Fragments/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Rats , Rats, Sprague-Dawley
6.
Nucl Med Commun ; 42(7): 800-810, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-33741860

ABSTRACT

OBJECTIVE: To analyze the fluorine-18 fludeoxyglucose PET/computed tomography (18F-FDG PET/CT) findings of retroperitoneal leiomyosarcoma (RLMS) and the role of this method in differentiating between benign and malignant masses and classifying the malignant degree to improve the understanding of this rare disease. METHODS: Eight leiomyomas (A group), 13 RLMSs (B group), and 20 postoperative recurrence/metastasis RLMSs (C group) were enrolled. PET/CT features of B group were analyzed. The differences of metabolic parameters between three groups were compared, receiver operating characteristic (ROC) curve analysis was performed to group A and B, and correlation analysis was performed to subgroup B. RESULTS: (1) The RLMS patients were more likely to be female, and PET/CT showed a high degree of heterogeneous metabolism in the soft tissue mass. (2) The standardized uptake value (SUV) of RLMS were significantly higher than those of benign leiomyomas (P < 0.05). The area under the ROC curve was 0.909, the sensitivity and specificity for diagnosing RLMS were 0.923 and 0.750, respectively, The SUVmax and SUVstd of primary RLMS were moderately associated with the Ki67 index. The mean SUVmax in the G1, G2 and G3 subgroups increased successively (4.15 ± 0.35, 6.47 ± 0.83, and 10.13 ± 4.29, respectively). (3) Primary RLMS was characterized by local invasion, but hematogenous metastasis and lymph node metastasis were rare. Postoperative recurrence/metastasis of RLMS was characterized by local recurrence and hematogenous metastasis, but lymph node metastasis was rare. CONCLUSION: PET/CT has potential value in the preoperative staging, benign and malignant differentiation, malignant degree classification and postoperative follow-up of RLMS.


Subject(s)
Leiomyosarcoma , Adult , Aged , Female , Fluorodeoxyglucose F18 , Humans , Lymphatic Metastasis , Male , Middle Aged , Positron Emission Tomography Computed Tomography
7.
BMC Anesthesiol ; 19(1): 6, 2019 01 08.
Article in English | MEDLINE | ID: mdl-30621601

ABSTRACT

BACKGROUND: It has been reported that postoperative cognitive dysfunction (POCD) is correlated with the degeneration of the central nervous system, oxidative stress, inflammation, and endocrine and immune dysfunction. Increased age, predisposed comorbidity, long surgery time, and prolonged stay in the intensive care unit have been reported to be risk factors for developing POCD for cardiac surgery. In the present study, the risk factors of early POCD after colorectal surgery were investigated. METHODS: Eighty patients, who provided informed consents for their participation in this study, were enrolled and received colorectal surgery under general anesthesia. Neuropsychological tests were performed preoperatively and on postoperative day seven. The risk factors for POCD were analyzed using a multivariate logistic regression model. RESULTS: Nineteen patients were diagnosed with POCD (24.7%). Diabetes history (OR = 8.391 [2.208-31.882], P = 0.012), fasting over 3 days after surgery (OR = 5.236 [1.998-13.721], P = 0.001) and an SIRS score of > 3 on the second day after surgery (OR = 6.995 [1.948-25.111], P = 0.003) were risk factors for early POCD in colorectal cancer patients. CONCLUSION: The risk factors for early POCD after colorectal surgery included diabetes history, fasting over 3 days, and an SIRS score of > 3 on the second day.


Subject(s)
Anesthesia, General/methods , Colorectal Neoplasms/surgery , Postoperative Cognitive Complications/epidemiology , Aged , Diabetes Mellitus/epidemiology , Fasting , Female , Humans , Male , Neuropsychological Tests , Prospective Studies , Risk Factors , Systemic Inflammatory Response Syndrome/diagnosis
8.
Onco Targets Ther ; 11: 7333-7343, 2018.
Article in English | MEDLINE | ID: mdl-30425523

ABSTRACT

BACKGROUND: The poor prognosis of colorectal cancer (CRC) largely results from local invasion and tumor metastases. Epithelial-mesenchymal transition (EMT) is a key step in the progression of solid tumors and plays a vital role in tumor metastasis. Recent studies demonstrate that C-X-C motif chemokine 11 (CXCL11) is involved in various cancers' progression. However, its biological activity in CRC needs deeper exploration. METHODS: The level of CXCL11 in CRC tissues and cell lines was determined using the quantitative real-time PCR (qRT-PCR) assay. The MTT, colony formation, wound healing and Transwell invasion assays were applied to assess the role of CXCL11 in CRC cell growth, migration and invasion, in vitro, respectively. A xenograft model was constructed to analyze the function of CXCL11 in CRC cell growth in vivo. RESULTS: CXCL11 was over-expressed in CRC tissues and cell lines. Repression of CXCL11 significantly inhibited CRC cell migration, invasion and EMT in vitro. In addition, down-regulation of CXCL11 reduced CRC cell growth and metastasis in vivo. Finally, we revealed that repression of CXCL11 inhibited the metastatic ability of CRC cell in a N-cadherin dependent manner. CONCLUSION: In summary, this study explicates the oncogenic activities of CXCL11 in CRC cell growth and metastasis.

9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 2260-2263, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30440856

ABSTRACT

A method of blocking neural signal for spasticity which is based on the antimissile strategy was proposed. When the pathological nerve action potential signal is detected at the proximal end of the nerve, such a potential signal that is opposite to the signal of the primary neural activity is applied at the distal end of the nerve at a proper delay so as to block the pathological nerve signal. Preliminary tests were performed on toad sciatic nerve-gastrocnemius specimens. Firstly, the effect of the distance between blocking electrodes on the blocking pulse voltage threshold was studied based on the electrical tension induced by the nerve signal on the controlled muscle. Then, the effective parameters of the blocking waveform were studied. Finally, the delay range of the blocking pulse compared to the pathogen action potential was studied. The results showed that in the sciatic nerve-gastrocnemius specimens, the most effective distance between the blocking electrode pairs was 5 mm and the anodic block required an inverted triangle waveform. The voltage threshold of an effective anodic blocking pulse was 1 V and the minimum pulse width was 90 ms. Under the condition of voltage threshold and minimum pulse width, the time shifting value of blocking pulse was greater than 1ms. It is concluded from the study that the spastic action potential caused by the disease can be effectively blocked, and limb muscle spasms can be eliminated under the action of appropriate electrode configuration and blocking signal waveforms.


Subject(s)
Extremities , Muscle Spasticity , Nerve Block , Action Potentials , Electric Stimulation , Extremities/physiology , Humans , Muscle Spasticity/prevention & control , Muscle Spasticity/therapy , Sciatic Nerve
10.
J Am Chem Soc ; 140(35): 11133-11140, 2018 09 05.
Article in English | MEDLINE | ID: mdl-30088768

ABSTRACT

Unconventional ion exchangers can achieve efficient removal of [UO2]2+, Cs+, and Sr2+ ions from complex aqueous solutions and are of great interest for environmental remediation. We report two new gallium thioantimonates, [Me2NH2]2[Ga2Sb2S7]·H2O (FJSM-GAS-1) and [Et2NH2]2[Ga2Sb2S7]·H2O (FJSM-GAS-2), which present excellent ion exchange properties for [UO2]2+, Cs+, and Sr2+ ions. They exhibit high ion exchange capacities for [UO2]2+, Cs+, and Sr2+ ions ( qmU = 196 mg/g, qmCs = 164 mg/g, and qmSr = 80 mg/g for FJSM-GAS-1, qmU = 144 mg/g for FJSM-GAS-2) and short equilibrium times for [UO2]2+ ion exchange (5 min for FJSM-GAS-1 and 15 min for FJSM-GAS-2, respectively). Both compounds display active ion exchange with [UO2]2+ in the pH range of 2.9-10.5. Moreover, the sulfide compounds could maintain high distribution coefficients KdU even in the presence of excess Na+, Ca2+, and HCO3-. The distribution coefficient KdU of 6.06 × 106 mL/g exhibited by FJSM-GAS-1 is the highest among the reported U adsorbents. The [UO2]2+-laden products can be recycled by conveniently eluting the uranium with a low-cost method. These advantages combined with facile synthesis, as well as ß and γ radiation resistance, make FJSM-GAS-1 and FJSM-GAS-2 promising for selective separations in nuclear waste remediation.

11.
Nat Prod Res ; 32(8): 933-938, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28880114

ABSTRACT

A new pair of sesamin-type lignan enantiomers (±)-morifolia A (1a/1b) together with eight known analogues (2-9) were isolated from the fruits of Morinda citrifolia. Their structures were established by spectroscopic data and the absolute configurations of 1a/1b were determined by ECD calculation. All compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and compounds 1a, 1b, 2-4 and 7-9 exhibited pronounced inhibition with IC50 values in the range of 1.97-8.01 (µM, being more active than the positive control, quercetin (IC50 = 15.32 (M).


Subject(s)
Dioxoles/chemistry , Lignans/chemistry , Morinda/chemistry , Animals , Cell Line , Circular Dichroism , Fruit/chemistry , Inhibitory Concentration 50 , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Nitric Oxide/biosynthesis , Stereoisomerism
12.
Am J Cancer Res ; 7(8): 1665-1679, 2017.
Article in English | MEDLINE | ID: mdl-28861323

ABSTRACT

Increasing evidence suggests that POU domain class 2 transcription factor 1 (POU2F1) participates in carcinogenesis and cancer progression via promotion of cell proliferation and metastasis; however, the functional role of POU2F1 in hepatocellular carcinoma (HCC) is largely unknown. In this study, we determined that POU2F1 was significantly up-regulated in HCC tumor tissue and cell lines. We demonstrated that POU2F1 over-expression promoted HCC cell proliferation, colony formation, migration, and invasion, while silencing of POU2F1 inhibited these malignant phenotypes. In vivo experiments indicated that knockdown of POU2F1 inhibited HCC cell metastasis and xenograft growth, whereas ectopic expression of POU2F1 promoted these cellular functions. Microarray analysis suggests that FAT atypical cadherin 1 (FAT1) can function downstream of POU2F1. Functionally, we demonstrated that POU2F1 knockdown induced growth suppression and metastasis inhibition of HCC cells and inactivated the FAT1 pathway, indicating that POU2F1 is a potential novel therapeutic target in HCC.

13.
J Rehabil Med ; 49(8): 629-636, 2017 Aug 31.
Article in English | MEDLINE | ID: mdl-28792587

ABSTRACT

OBJECTIVE: The electromyographic bridge (EMGB) detects surface electromyographic signals from a non-paretic limb. It then generates electric pulse trains according to the electromyographic time domain features, which can be used to stimulate a paralysed or paretic limb in real time. This strategy can be used for the contralateral control of neuromuscular electrical stimulation (NMES) to improve motor function after stroke. The aim of this study was to compare the treat-ment effects of EMGB vs cyclic NMES on wrist and finger impairments in subacute stroke patients. METHODS: A total of 42 hemiplegic patients within 6 months of their cerebrovascular accidents were randomly assigned to 4-week treatments with EMGB or cyclic NMES. Each group underwent a standard rehabilitation programme and 10 sessions per week of hand training with EMGB or cyclic NMES. Outcome measures were: Brunnstrom stage, upper extremity components of the Fugl-Meyer Assessment, Motor Status Scale, voluntary surface electromyographic ratio and active range of motion of the wrist and finger joints. RESULTS: The EMGB group showed significantly greater improvements than the cyclic NMES group on the following measures: Brunnstrom stages for the hand, upper extremity - Fugl-Meyer Assessment, Motor Status Scale, and the voluntary surface electromyographic ratio of wrist and finger extensors. Eleven and 4 participants of the EMGB group who had no active wrist and finger movements, respectively, at the start of the treatment could perform measurable wrist and finger extensions after EMGB training. The corresponding numbers in the cyclic NMES group were only 4 and 1. CONCLUSION: In the present group of subacute stroke patients, the results favour EMGB over cyclic NMES for augmenting the recovery of volitional wrist and finger motion.


Subject(s)
Electric Stimulation Therapy/methods , Electromyography/methods , Hand/physiopathology , Stroke Rehabilitation/methods , Stroke/therapy , Female , Humans , Male , Middle Aged
14.
J Am Chem Soc ; 139(12): 4314-4317, 2017 03 29.
Article in English | MEDLINE | ID: mdl-28260379

ABSTRACT

Exploring new ion-exchangers for the recovery of rare earth elements (REEs) and recycling is worthwhile for the high-tech industry and an eco-friendly sustainable economy. The efficient enrichment of low concentration REE from complex aqueous solutions containing large excess of competitive ions is challenging. Here we present a chalcogenide example as a superior REE ion-exchanger efficiently removing them from very complex aqueous solutions, (Me2NH2)1.33(Me3NH)0.67 Sn3S7·1.25H2O (FJSM-SnS). The material exhibits fast and efficient ion exchange behavior with short equilibrium time (<5 min), high adsorption capacity (139 mg/g for Eu, 147 mg/g for Tb, 126 mg/g for Nd), wide pH resistance (1.9-8.5), the largest distribution coefficient (Kd) value of 6.5 × 106 mL/g, good selectivity against Al3+, Fe3+, and Na+ ions, and high recovery rate (>99%) at low concentrations. Moreover, after ion-exchange, the REE in corresponding exchanged products could be easily recovered by elution. FJSM-SnS has superior capacity and faster absorption kinetics than other states of the artificial REE sorbents such as Al2O3/EG, clay minerals, zeolite, and activated carbon.

15.
Article in English | MEDLINE | ID: mdl-25960755

ABSTRACT

Deqi refers to the special sensation and reaction sensed mainly by both acupuncturist and patient when a needle was inserted into the acupoints and is considered to be vital to achieve acupuncture effect. For acupuncturist, it is important to judge and control Deqi in clinical practice. However, enough attention is paid to patients' feelings rather than acupuncturists' nowadays. We thus conducted this survey to determine acupuncturists' perspectives about Deqi and to further find the proper way to induce Deqi. A total of 250 questionnaires were sent out to acupuncturists and 202 (80.8%) were returned. According to the results, most acupuncturists believe that Deqi is vital to obtain preferable clinical effects. The reliability of acupuncturists' Deqi sensation ranks as sinking> tightening> astringent. The reliability of patients' Deqi sensations ranks as sourness> numbness> distention> heaviness> pain. The reliability of influential factors ranks as manipulation> specificity of acupoint> TCM constitution> disease status> patient's psychological condition> acupuncturists' psychological guidance> clinical environment. This study is believed to provide additional evidence to the qualitative and quantitative research of Deqi in the future.

16.
Int J Med Sci ; 12(1): 17-22, 2015.
Article in English | MEDLINE | ID: mdl-25552914

ABSTRACT

OBJECTIVE: The aim of this study was to quantify the copies of circulating nucleophosmin (NPM) mutations DNA in the plasma of patients with acute myeloid leukemia (AML) and to explore the association of circulating NPM mutation levels with clinical characteristics. DESIGN AND METHODS: The presence of NPM mutations in 100 Chinese patients newly diagnosed with AML were identified by RT-PCR and sequencing analysis. Copies of circulating NPM mutation A (NPM mut.A) DNA in the plasma of mutation-positive cases were quantified by real-time quantitative PCR (qRT-PCR). Furthermore, the association of circulating NPM mutation levels and clinical characteristics was analyzed. RESULTS: NPM mutations were identified in 37 of the 100 patients and all cases were NPM mut.A. The circulating NPM mut.A levels ranged from 0.35×10(8) copies/ml to 6.0×10(8) copies/ml in the 37 mutation-positive cases. The medium and quartile M (P25, P75) of the circulating NPM mut.A levels in patients classified as M2, M4 and M5 morphological subtypes were 1.35×10(8) (0.76×10(8), 1.91×10(8)) copies/ml, 1.81×10(8) (1.47×10(8), 2.2×10(8)) copies/ml and 2.50×10(8) (2.42×10(8), 3.05×10(8)) copies/ml, respectively. Circulating NPM mut.A levels were significantly higher in patients with the M5 subtype of AML compared to patients with the M2 and M4 subtypes (p=0.000, p=0.046). In addition, circulating NPM mut.A copies were significantly associated with a higher white blood cell count, platelet count and bone marrow blast percentage (p<0.05). CONCLUSION: Our results suggest that circulating NPM mutations DNA assay serves as a complementary to the routine investigative protocol of NPM-mutated leukemia.


Subject(s)
Leukemia, Myeloid, Acute/genetics , Mutation , Nuclear Proteins/genetics , Adolescent , Adult , DNA/blood , DNA Mutational Analysis/methods , Female , Humans , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/pathology , Leukocyte Count , Male , Middle Aged , Nuclear Proteins/blood , Nucleophosmin , Platelet Count , Real-Time Polymerase Chain Reaction/methods , Young Adult
17.
Int J Med Sci ; 8(4): 309-14, 2011.
Article in English | MEDLINE | ID: mdl-21611112

ABSTRACT

Nucleophosmin (NPM1) gene mutations resulting in cytoplasmic delocalization of Nucleophosmin (NPMc+) are the most common genetic alteration in acute myeloid leukemia (AML). Here, we attempted to prepare monoclonal antibodies (mAbs) against NPM1 mutation A (NPM-mA) and investigated the mAbs' clinical utility in immunohistochemical detection of NPMc+AML. The pET-32a-NPM-mA vector with the whole open reading frame of the NPM-mA gene was constructed. E.coli BL21 transformed with the vector were induced to express the NPM-mA recombinant protein. BALB/c mice were immunized with the recombinant NPM-mA. Positive clones were selected by indirect ELISA and the mAbs were obtained. Immunohistochemistry was performed to detect the NPMc+ in bone marrow smears from 10 AML patients with NPM-mA. The results showed that the pET-32a-NPM-mA vector was successfully constructed and the NPM-mA recombinant protein was used to immunize the mice. Two positive clones (2G3 and 3F9) were selected. The mAbs against NPM-mA were raised, but did cross-react with wild type NPM1. The mAbs can be used to detect the cytoplasmic dislocation of NPM1 in all AMLs carrying NPM-mA. Our results show that anti-NPM-mA mAbs were produced. Though they would cross-react with wild type NPM1, the mAbs may still have potential in the detection of NPMc+AMLs.


Subject(s)
Antibodies, Monoclonal/immunology , Immunohistochemistry/methods , Leukemia, Myeloid, Acute/diagnosis , Nuclear Proteins/analysis , Animals , Antibodies, Monoclonal/genetics , Female , Humans , Leukemia, Myeloid, Acute/genetics , Mice , Mice, Inbred BALB C , Mutation , Nuclear Proteins/genetics , Nuclear Proteins/immunology , Nucleophosmin , Recombinant Proteins/genetics , Recombinant Proteins/immunology
18.
Exp Mol Pathol ; 90(1): 38-44, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21122805

ABSTRACT

Nucleophosmin (NPM1) plays key roles in ribosome biogenesis, centrosome duplication, and maintenance of genomic integrity. NPM1 mutations have been recently identified as the most frequent genetic alteration in acute myeloid leukemia and are related to leukemogenesis. NPM1 mutations are involved in the regulation of cell proliferation, cell cycle, and apoptosis. However, the oncogenic potential of NPM1 mutations is not fully understood. Here, we investigated the change of cell migration and invasion in vitro and the role of NPM1 mutations in this process. In our study, NIH3T3 cells were transfected with plasmids encoding NPM1 mutation A (NPM1 mA), and the cell chemotactic response in vitro was evaluated by cell migration and invasion assays. In addition, the expression levels of MMP-2, MMP-9 and CXCR4 were assayed by quantitative real-time PCR and western blotting. Our findings suggested that the migration and invasion of NIH3T3 cells were significantly enhanced after transfection with NPM1 mA (p<0.01). Furthermore, there was greater expression of MMP-9 and CXCR4 (p<0.01), but a lower expression of MMP-2 in the NPM1 mA group. These results demonstrate that NPM1 mutations may promote cell migration and invasion in vitro, and MMP-9 and CXCR4 may be involved in the regulation of cell invasion. Thus, this study sheds new light on the effect of NPM1 mutations on leukemogenesis.


Subject(s)
Cell Movement/genetics , Matrix Metalloproteinases/metabolism , Mutation , Nuclear Proteins/genetics , Receptors, CXCR4/physiology , Animals , Cell Proliferation , Matrix Metalloproteinases/genetics , Mice , NIH 3T3 Cells , Neoplasm Invasiveness/genetics , Nucleophosmin , Plasmids/genetics , Receptors, CXCR4/genetics , Transfection/methods
19.
Clin Chem Lab Med ; 48(11): 1651-6, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20831457

ABSTRACT

BACKGROUND: Increased cell-free DNA (cf-DNA) and the integrity of cf-DNA in plasma of patients with cancer has been described. We investigated the clinical utility of cf-DNA in the detection and monitoring of progression of leukemia. METHODS: Plasma samples from 60 patients with acute leukemia were analyzed in comparison to plasma from 30 healthy controls. Plasma DNA was determined by quantitative PCR (qPCR) by amplifying the ß-actin gene (ACTB). The DNA integrity index was calculated as the ratio of qPCR results (ACTB384/106). Paired diagnostic/complete remission (CR)/relapse samples from eight of 60 patients were analyzed, and the minimum residual disease (MRD) situations were monitored. RESULTS: DNA concentrations (median: 8.80 ng/mL, p=0.004) and DNA integrity (median: 0.51, p<0.001) in cancer patients were significantly higher. Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve of DNA and DNA integrity were 0.79 and 0.88, respectively. DNA integrity at CR had a distinct reduction and then an increase at relapse. DNA integrity in CR cases was higher than that observed in healthy controls. CONCLUSIONS: Our preliminary data suggest that plasma DNA integrity is increased in acute leukemia and may be a potential biomarker for monitoring MRD. However, more work is needed.


Subject(s)
DNA/blood , Leukemia/blood , Adult , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Case-Control Studies , Cell-Free System , DNA/genetics , Disease Progression , Humans , Leukemia/diagnosis , Middle Aged , Polymerase Chain Reaction , Prognosis , Young Adult
20.
Int J Biol Sci ; 6(5): 419-27, 2010 Aug 03.
Article in English | MEDLINE | ID: mdl-20714440

ABSTRACT

Recent studies have reported that cancer stem cells (CSCs) could be isolated from solid cancer cell lines, in which the purity of CSCs was higher than that from tumor tissues. Separation of CSCs from leukemic cell lines was rarely reported. In this study, CD34(+)CD38(-)stem-like cell subsets in human KG-1a leukemic cell line were enriched by cytotoxic agent 5-fluorouracil (5-FU). After 4 days incubation of KG-1a cell line with 5-FU (50 microg/ml), the CD34(+)CD38(-) subpopulation of cell lines was enriched more than 10 times. The enriched cells had proliferate potential in vitro, low level of RNA transcription and Hoechst 33342 dye efflux ability, accompanied by high expression of ATP-binding cassette transporter protein ABCG2. Our findings suggest that treatment with 5-FU offers an easy method to isolate leukemic stem-like subpopulation. It can facilitate studies of leukemic stem cell biology and the development of new therapeutic strategies.


Subject(s)
Cell Culture Techniques , Fluorouracil/pharmacology , Leukemia/pathology , Neoplastic Stem Cells/drug effects , ADP-ribosyl Cyclase 1/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters/metabolism , Antigens, CD34/metabolism , Benzimidazoles/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , DNA/metabolism , Humans , Leukemia/genetics , Leukemia/metabolism , Neoplasm Proteins/metabolism , RNA/metabolism , Transcription, Genetic/drug effects
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