RESUMO
Increased macrophage phagocytosis of antibody-coated platelets, as well as decreased numbers and/or impaired function of CD4+CD25+Foxp3+ regulatory T (Treg) cells, has been shown to participate in the pathogenesis of immune thrombocytopenia (ITP). Low-dose histone deacetylase inhibitors (HDACi's) are anti-inflammatory and immunomodulatory agents that can enhance immunosuppression in graft-versus-host disease by increasing the number and function of Foxp3+ Treg cells, but it is unclear whether they have the potential to promote immune tolerance and platelet release in ITP. In this study, we performed in vitro and in vivo experiments and found that a low-dose HDACi (chidamide) alleviated thrombocytopenia in passive and active murine models of ITP. Further, low-dose HDACi's attenuated macrophage phagocytosis of antibody-coated platelets, stimulated the production of natural Foxp3+ Treg cells, promoted the peripheral conversion of T cells into Treg cells, and restored Treg cell suppression in vivo and in vitro. Finally, we confirmed that low-dose HDACi's could regulate CTLA4 expression in peripheral blood mononuclear cells through modulation of histone H3K27 acetylation. Low-dose HDACi treatment in ITP could be offset by blocking the effect of CTLA4. Therefore, we propose that low-dose chidamide administration has potential as a novel treatment for ITP in the clinic.
Assuntos
Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Tolerância Imunológica/imunologia , Leucócitos Mononucleares/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , Linfócitos T Reguladores/imunologia , Acetilação , Adulto , Idoso , Animais , Antígeno CTLA-4/metabolismo , Relação Dose-Resposta a Droga , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Tolerância Imunológica/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Prognóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Adulto JovemRESUMO
This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P = .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P < .01). There was no difference between these 2 groups in terms of the long-term response (P = .12). Our findings demonstrated that the combination of RTX and rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836.
Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/terapia , Trombopoetina/administração & dosagem , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Autoanticorpos/sangue , Criança , Terapia Combinada , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Recidiva , Rituximab , Trombopoetina/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To analyze the DTA (DNMT3A, TET2, ASXL1) mutations in patients with myeloproliferative neoplasms (MPN), and preliminarily explore their correlation with thromboembolism. METHODS: Clinical characteristics of 62 patients diagnosed de novo MPN at Central Hospital Affiliated to Shandong First Medical University from September 2016 to September 2022 were retrospectively analyzed. Next-generation sequencing was used to detect 35 MPN-related genes, and the DTA mutations in MPN patients and their relationship with thromboembolic events were analyzed. RESULTS: 75.8% (47/62) of the patients presented pathogenic non-driver mutations, and the mean number of pathogenic non-driver mutations per patient was 1.08. Among them, the most frequently mutated non-driver genes were TET2 (38.7%, 24/62), DNMT3A (9.7%, 6/62) and ASXL1 (6.5%, 4/62). The presence of DTA gene mutations was 50% (31/62) in the total MPN patients, and mainly accompanied by driver mutations. The mutation rate of DTA in patients aged ≥60 years was significantly higher than that in patients <60 years old (P =0.039). The incidence of thromboembolism in patients with DTA mutation was 58.1% (18/31), which was significantly higher than that in patients without DTA mutation (19.4%, 6/31) (P =0.002). The TET2 gene mutation rate in MPN patients with thromboembolism was 66.7% (16/24), which was significantly higher than that in patients without thromboembolism (21.1%, 8/38) (P =0.00). CONCLUSION: Patients with MPN have a higher incidence of DTA mutations, which are mainly accompanied by driver gene mutations. The incidence of thromboembolism in MPN patients with DTA mutations is higher than that in patients without DTA mutations. Especially, the elderly (≥60 years) essential thrombocythemia(ET) and polycythemia vera(PV) patients with TET2 mutation should be vigilant for thromboembolic events.
Assuntos
DNA Metiltransferase 3A , Proteínas de Ligação a DNA , Dioxigenases , Mutação , Transtornos Mieloproliferativos , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Tromboembolia , Humanos , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/complicações , Tromboembolia/genética , Estudos Retrospectivos , Proteínas Proto-Oncogênicas/genética , Proteínas de Ligação a DNA/genética , Proteínas Repressoras/genética , DNA (Citosina-5-)-Metiltransferases/genética , Masculino , Feminino , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
BACKGROUND: Insect chitinases play vital roles in postembryonic development, especially during the molting process, and are potential targets for the RNA interference (RNAi)-based insecticidal strategy. Systematic functional analyses of chitinase genes have already been conducted on numerous insect pests, but similar analyses have not been carried out on Diaphorina citri. RESULTS: Eleven chitinase/chitinase-like genes and one endo-ß-N-acetylglucosaminidase (ENGase) gene were identified in the Diaphorina citri genome using various bioinformatic tools. Transcriptomes of the integument and midgut from fifth-instar nymphs and freshly-emerged adults of Diaphorina citri were generated and sequenced. Potential functions of 12 chitinase/chitinase-like genes were examined during nymph-adult transitions. Four chitinase genes, including DcCht5, DcCht7, DcCht10-1 and DcCht10-2, were mainly expressed in the integument of fifth-instar nymphs. These four genes were also up-regulated significantly under 20-hydroxyecdysone (20E) treatments. RNAi-mediated knockdown of these four genes suggests that they are essential for nymph-adult transition. CONCLUSION: Our results demonstrated essential roles of the chitinase/chitinase-like genes during the nymph-adult transition in Diaphorina citri, which are potentially useful targets for controlling the Diaphorina citri pest. © 2022 Society of Chemical Industry.
Assuntos
Quitinases , Hemípteros , Animais , Quitinases/genética , Muda/genética , Ninfa/genética , Interferência de RNARESUMO
The objective of this study was to investigate the variation of HSP70 mRNA level in dairy cows and relationships of its closely linked microsatellite loci with heat tolerance traits. Blood samples were collected from ten healthy Holstein cows with the same age and milking stage at different temperatures-humid-index (THI) (86.2, high temperature; 70.9, critical high temperature, and 56.8, optimum temperature). The mRNA levels of HSP70 of lymphocytes in peripheral blood were analyzed using real-time RT-PCR. The mRNA level of HSP70 was increased with the THI; the mRNA level of HSP70 at high temperature was higher than others (P<0.01). This indicated that the bovine HSP70 gene may act as a potential can-didate gene for response to heat shock. Genetic variation of three microsatellite loci BMS468, BM1258, and BM1815, which were closely linked to HSP70 gene on chromosome 23, was analyzed in 160 Holstein cows with non-denaturing poly-acrylamide gel electrophoresis. The association between these microsatellite loci and heat tolerance traits were analyzed by least square linear model. The results showed that 134 bp/128 bp at BMS468 and 186 bp/148 bp at BM1815 were the most favorable genotypes for HTC, red cell potassium, and decrement rate of milk yield in high temperature (P<0.05); 101 bp/99 bp at BM1258 was the most favorable genotype for decrement rate of milk yield in high temperature (P<0.05).
Assuntos
Proteínas de Choque Térmico HSP70/genética , Temperatura Alta , Repetições de Microssatélites/genética , Leite/metabolismo , RNA Mensageiro/fisiologia , Animais , Bovinos , Feminino , Linfócitos/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TemperaturaRESUMO
Genetic variation of three microsatellite loci BMS2258, SOD1, and BM723, which were closely correlated with GSH-Px, SOD, and Na+/K+-ATPase genes, was analyzed in 130 Holstein cows by PCR and nondenaturing polyacrylamide gel-electrophoresis. Polymorphic information content, effective number of alleles and heterozygosity of these microsatellite loci were determined. Relationships of the three microsatellite loci with enzyme activities and daily milk yields in Holstein cows were analyzed by least squares linear model. The results showed significant correlations of the three microsatellite loci with their corresponding enzyme activities and daily milk yield in summer and fall (Plt;0.05). The least square means of GSH-Px activities and daily milk yields for BMS2258 (182 bp/164 bp), SOD activities for SOD1 (148 bp/148 bp), and daily milk yields for SOD1 (148 bp/146 bp), Na+/K+-ATPase activities and daily milk yields for BM723 (161 bp/111 bp) were relatively higher. These genotypes were the most favorable genotypes for enzyme activity and daily milk yields in summer and fall, which could be references for marker assisted selection in heat resistance traits in dairy cattle.
Assuntos
Bovinos/genética , Bovinos/metabolismo , Enzimas/genética , Enzimas/metabolismo , Repetições de Microssatélites/genética , Leite/metabolismo , Estações do Ano , Animais , Cromossomos/genética , Feminino , Genótipo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Reação em Cadeia da Polimerase , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of antipsychotics to augment serotonin reuptake inhibitors (SRIs) for treatment-resistant obsessive-compulsive disorder (OCD) in adults. PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched on September 8, 2018. Randomized controlled trials investigating antipsychotics as augmentation agents were included. Network meta-analyses were performed using frequentist methods. Efficacy was measured by the Yale-Brown Obsessive-Compulsive Scale. Tolerability was measured by side-effect discontinuations. Mean differences (MDs) and odds ratios (ORs) were reported with 95% confidence intervals (CIs). Twenty articles with 790 patients were included. Our analyses showed that there was no significant difference in efficacy between antipsychotic agents. The order of efficacy rankings was inconsistent between primary analysis and sensitivity analyses. We found that there was considerable heterogeneity between studies. Comorbid tics was identified as a significant moderator. All antipsychotics except paliperidone were significantly superior to placebo in the subgroup without comorbid tics, while no antipsychotics was significantly superior to placebo in the comorbid tics subgroup. With respect to tolerability, quetiapine (OR, 3.45; 95% CI, 1.04-11.11) and paliperidone (20.00; 1.01->100) were significantly less tolerable than placebo. Based on this network meta-analysis, antipsychotic agents as augmentations to SRIs might be more effective in treatment-resistant OCD patients without comorbid tics. Definitive determination of which drug is optimal cannot be drawn currently because of the limited numbers of studies and heterogeneity across studies.
Assuntos
Antipsicóticos/farmacologia , Pesquisa Comparativa da Efetividade , Sinergismo Farmacológico , Metanálise em Rede , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Antipsicóticos/administração & dosagem , Quimioterapia Combinada , Humanos , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagemRESUMO
BACKGROUND: Various agents for augmentation of serotonin reuptake inhibitors have been investigated for treatment-resistant obsessive-compulsive disorder (OCD). We aimed to comprehensively compare different augmentation agents for treatment-resistant OCD in adults. METHODS: PubMed, Embase, Web of Science, CENTRAL, the WHO's ICTRP, and ClinicalTrials.gov were searched on February 20, 2018. Pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcome was efficacy measured by the Yale-Brown Obsessive Compulsive Scale. The secondary outcomes were tolerability (side-effect discontinuation) and acceptability (all cause discontinuation). Mean differences (MDs) and odds ratios (ORs) were reported with 95% confidence intervals (CIs). RESULTS: Thirty-three articles with 34 trials (1216 patients) were included. Memantine (MD, -8.94; 95% CI, -14.42 to -3.42), risperidone (-4.47, -8.75 to -0.17), topiramate (-6.05, -10.89 to -1.20), lamotrigine (-6.07, -11.61 to -0.50), and aripiprazole (-5.14, -9.95 to -0.28) were significantly superior to placebo. Antipsychotic (-4.09, -6.22 to -1.93) and glutamatergic (-5.22, -7.53 to -2.84) agents were significantly superior to placebo. Considerable heterogeneity was found across studies, and baseline symptom severity was identified as a significant moderator. After baseline severity adjustment, quetiapine (-5.00, -8.59 to -1.29) and olanzapine (-8.28, -15.34 to -1.13) became significantly superior to placebo. CONCLUSIONS: Our study supports the use of antipsychotic or glutamatergic agents as augmentation agents for treatment-resistant OCD. Topiramate, lamotrigine, aripiprazole, olanzapine, risperidone, memantine, and quetiapine are alternative augmentation drugs; however, a definitive conclusion of the best drug remains undetermined because of the considerable heterogeneity and limited numbers of studies and patients for each agent.
Assuntos
Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Psicotrópicos/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resistência a Medicamentos , Quimioterapia Combinada , Humanos , Metanálise em RedeRESUMO
In Locusta migratoria, we found that two chitin biosynthesis genes, UDP N-acetylglucosamine pyrophosphorylase gene LmUAP1 and chitin synthase gene LmCHS1, are expressed mainly in the integument and are responsible for cuticle formation. However, whether these genes are regulated by 20-hydroxyecdysone (20E) is still largely unclear. Here, we showed the developmental expression pattern of LmUAP1, LmCHS1 and the corresponding 20E titer during the last instar nymph stage of locust. RNA interference (RNAi) directed toward a common region of the two isoforms of LmEcR (LmEcRcom) reduced the expression level of LmUAP1, while there was no difference in the expression of LmCHS1. Meantime, injection of 20E in vivo induced the expression of LmUAP1 but not LmCHS1. Further, we found injection-based RNAi of LmEcRcom resulted in 100% mortality. The locusts failed to molt with no apolysis, and maintained in the nymph stage until death. In conclusion, our preliminary results indicated that LmUAP1 in the chitin biosynthesis pathway is a 20E late-response gene and LmEcR plays an essential role in locust growth and development, which could be a good potential target for RNAi-based pest control.
Assuntos
Quitina Sintase/metabolismo , Ecdisterona/metabolismo , Regulação da Expressão Gênica , Locusta migratoria/metabolismo , Nucleotidiltransferases/metabolismo , Animais , Quitina/biossíntese , Quitina Sintase/genética , Feminino , Hemolinfa/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Locusta migratoria/genética , Locusta migratoria/crescimento & desenvolvimento , Masculino , Nucleotidiltransferases/genética , Ninfa/enzimologiaRESUMO
BACKGROUND: This study was conducted to evaluate the short-term therapeutic effects of using repeated transcranial magnetic stimulation (rTMS) to treat obsessive-compulsive disorder (OCD) and to examine potential influencing factors. METHOD: We searched the PubMed, EMBASE, CENTRAL, Wanfang, CNKI, and Sinomed databases on September 18, 2016 and reviewed the references of previous meta-analyses. Sham-controlled, randomized clinical trials using rTMS to treat OCD were included. Hedge's g was calculated for the effect size. Subgroup analyses and univariate meta-regressions were conducted. RESULTS: Twenty studies with 791 patients were included. A large effect size (g=0.71; 95%CI, 0.55-0.87; P<0.001) was found for the therapeutic effect. Targeting the supplementary motor area (SMA) (g=0.56; 95%CI, 0.12-1.01; P<0.001), left dorsolateral prefrontal cortex (DLPFC) (g=0.47; 95%CI, 0.02-0.93; P=0.02), bilateral DLPFC (g=0.65; 95%CI, 0.38-0.92; P<0.001) and right DLPFC (g=0.93; 95%CI, 0.70-1.15; P<0.001), excluding the orbitofrontal cortex (OFC) (g=0.56; 95%CI, -0.05-1.18; P=0.07), showed significant improvements over sham treatments. Both low-frequency (g=0.73; 95%CI, 0.50-0.96; P<0.001) and high-frequency (g=0.70; 95%CI, 0.51-0.89; P<0.001) treatments were significantly better than sham treatments, with no significant differences between the effects of the two frequencies. The subgroup analyses indicated that patients who were non-treatment resistant, lacked concurrent major depressive disorder (MDD) and received threshold-intensity rTMS showed larger therapeutic effects than the corresponding subgroups. The subgroup analysis according to sham strategy showed that tilted coils yielded larger effects than sham coils. Meta-regression analyses revealed that none of the continuous variables were significantly associated with the therapeutic effects. LIMITATIONS: Only short-term therapeutic effects were assessed in this study. CONCLUSIONS: Based on this study, the short-term therapeutic effects of rTMS are superior to those of sham treatments. The site of stimulation, stimulation frequency and intensity and sham condition were identified as potential factors modulating short-term therapeutic effects. The findings of this study may inspire future research.
Assuntos
Transtorno Obsessivo-Compulsivo/terapia , Estimulação Magnética Transcraniana , Humanos , Córtex Pré-FrontalRESUMO
OBJECTIVE: To analyse the relationship of T lymphocyte and granulocyte chimerism following allogeneic peripheral blood cell transplantation and the occurrence of relapse, graft failure and graft versus host disease. METHODS: 21 patients underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Fluorescence-activated cell sorter (FACS) sorted CD3+ T lymphocytes and CD15+ granulocyte from peripheral blood of all the patients were analyzed for short tandem repeats in 7 days interval for 1 month starting from the day of PBSCT, then 1 month interval for 6 months, and then 3 months interval to the end of one year. RESULTS: Chimerism of granulocyte was higher than T lymphocyte on day 7 posttransplant in 4 patients given myeloablative conditioning. The median donor chimerism of granulocyte and T lymphocyte was 95% and 55% respectively. The other 17 patients had higher chimerism of T lymphocyte than granulocyte on day 7, which was 60% (15%-76%) and 0% (0%-40%) respectively. 20 patients reached complete donor chimerism (CDC) on day 21 (14-102 days) for T lymphocyte and on day 14 for granulocyte, except one relapsed on day 28. Seven patients had decreasing mixed chimerism when disease relapsed or graft failure occurred. T cell donor chimerism decreased earlier than myeloid cells, however, bone marrow sample and granulocyte still remained in complete donor chimerism or stable mixed chimerism, bone marrow smear showed normal at the same time. CONCLUSION: Blood leukocyte subset chimerism analysis, especially T cell chimerism analysis may provide earlier information of engraftment, relapse and graft failure than blood and bone marrow samples, therefore immunomodulatory therapies may be given to recipients earlier and overall survival may be improved.
Assuntos
Transplante de Células-Tronco de Sangue Periférico , Subpopulações de Linfócitos T/imunologia , Quimeras de Transplante/imunologia , Adulto , Feminino , Citometria de Fluxo , Seguimentos , Rejeição de Enxerto/etiologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante HomólogoRESUMO
Insect chitinases are involved in degradation of chitin from the exoskeleton or peritrophic metrix of midgut. In Locusta migratoria, two duplicated Cht5s (LmCht5-1 and LmCht5-2) have been shown to have distinct molecular characteristics and biological roles. To explore the protein properties of the two LmCht5s, we heterologously expressed both enzymes using baculovirus expression system in SF9 cells, and characterized kinetic and carbohydrate-binding properties of purified enzymes. LmCht5-1 and LmCht5-2 exhibited similar pH and temperature optimums. LmCht5-1 has lower Km value for the oligomeric substrate (4MU-(GlcNAc)3 ), and higher Km value for the longer substrate (CM-Chitin-RBV) compared with LmCht5-2. A comparison of amino acids and homology modeling of catalytic domain presented similar TIM barrel structures and differentiated amino acids between two proteins. LmCht5-1 has a chitin-binding domain (CBD) tightly bound to colloidal chitin, but LmCht5-2 does not have a CBD for binding to colloidal chitin. Our results suggested both LmCht5-1 and LmCht5-2, which have the critical glutamate residue in region II of catalytic domain, exhibited chitinolytic activity cleaving both polymeric and oligomeric substrates. LmCht5-1 had relatively higher activity against the oligomeric substrate, 4MU-(GlcNAc)3 , whereas LmCht5-2 exhibited higher activity toward the longer substrate, CM-Chitin-RBV. These findings are helpful for further research to clarify their different roles in insect growth and development.
Assuntos
Quitinases/metabolismo , Proteínas de Insetos/metabolismo , Locusta migratoria/enzimologia , Animais , Quitina/química , Quitinases/química , Quitinases/genética , Proteínas de Insetos/química , Proteínas de Insetos/genética , Cinética , Ligação Proteica , Células Sf9RESUMO
OBJECTIVE: To investigate the IL-32 mRNA expression of bone marrow stromal cells and its correlation with apoptosis of bone marrow mononuclear cells in patients with myelodysplastic syndrome (MDS). METHODS: Bone marrow samples from 26 MDS patients and 10 iron deficiency anemia (IDA, as control) patients were collected, RT-PCR was used to detect the IL-32 mRNA expression of bone marrow stromal cells, and the apoptosis of bone marrow mononuclear cells was detected by flow cytometry with Annexin V-FITC/PI dowble staining. The born marrow lymphocytes and NK cells were detected by means of direct immunofluorescence labeling whole blood hemolysis and flow cytometry. RESULTS: IL-32 mRNA expression of bone marrow stromal cells in the MDS patients was significantly higher than that of control group, the IL-32 mRNA expression of bone marrow stromal cells in patients with RA, RAS and RCMD was significantly higher than that in patients with RAEB. There was no obvious difference between RAEB and the control groups. The apoptosis of bone marrow mononuclear cells in MDS group was significantly higher than that in the control group, the apoptosis of bone marrow mononuclear cells in patients with RA, RAS and RCMD was significantly higher than that in RAEB. There was no significant difference between RAEB group and control group. The IL-32 mRNA expression in bone marrow stromal cells significantly correlated with the apoptosis of bone marrow mononuclear cells in MDS patients. The NK cell number in born marrow of MDS patients and the control group had no significant difference. CONCLUSION: The expression of IL-32 mRNA in bone marrow stromal cells significantly relates with the apoptosis of MDS cells, and the secretion of IL-32 by bone marrow stromal cells may be one of the reasons for the apoptosis of MDS bone marrow cells. It is speculated that the abnormal MDS bone marrow microenvironment is involved in the apoptosis of bone marrow cells.
Assuntos
Apoptose , Interleucinas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Síndromes Mielodisplásicas/patologia , Células da Medula Óssea/metabolismo , Citometria de Fluxo , Humanos , RNA Mensageiro/metabolismoRESUMO
ß-N-acetylglucosaminidases are crucial enzymes involved in chitin degradation in insects. We identified a ß-N-acetylglucosaminidase gene (LmNAG1) from Locusta migratoria. The full-length complementary DNA (cDNA) of LmNAG1 consists of 2 667 nucleotides, including an open reading frame (ORF) of 1 845 nucleotides encoding 614 amino acid residues, and 233- and 589-nucleotide non-coding regions at the 5'- and 3'-ends, respectively. Phylogenetic analysis grouped the cDNA-deduced LmNAG1 protein with the enzymatically characterized ß-N-acetylglucosaminidases in group I. Analyses of stage- and tissue-dependent expression patterns of LmNAG1 were carried out by real-time quantitative polymerase chain reaction. Our results showed that LmNAG1 transcript level in the integument was significantly high in the last 2 days of the fourth and fifth instar nymphs. LmNAG1 was highly expressed in foregut and hindgut. RNA interference of LmNAG1 resulted in an effective silence of the gene and a significantly reduced total LmNAG enzyme activity at 48 and 72 h after the injection of LmNAG1 double-stranded RNA (dsRNA). As compared with the control nymphs injected with GFP dsRNA, 50% of the dsLmNAG1-injected nymphs were not able to molt successfully and eventually died. Our results suggest that LmNAG1 plays an essential role in molting process of L. migratoria.
Assuntos
Acetilglucosaminidase/genética , Proteínas de Insetos/genética , Locusta migratoria/enzimologia , Muda , Interferência de RNA , Acetilglucosaminidase/metabolismo , Animais , Sequência de Bases , Proteínas de Insetos/metabolismo , Locusta migratoria/classificação , Locusta migratoria/genética , Locusta migratoria/crescimento & desenvolvimento , Dados de Sequência Molecular , FilogeniaRESUMO
This study was aimed to detect the mutations and microsatellite instability (mtMSI) in mitochondrial DNA (mtDNA) D-loop region in bone marrow cells of acute leukemia (AL) patients, and to analyze their relationship with the pathogenesis of AL. 19 cases of newly diagnosed AL were enrolled in this study. Through extracting mtDNA, the D-loop region was amplified by polymerase chain reaction (PCR), the sequences of PCR products were detected by the pros- and cons-direct sequencing methods. The sequencing results were compared with the revised Cambridge reference sequence (rCRS) and the relevant database (MITOMAP database, GenBank database, mtDB database). The results showed that the mutation rate of mtDNA D-loop region in AL was 79% (15/19). 215 variations (35 mutations, 180 SNP) and a kind of mtMSI in the D-loop region were detected. A new type of mutation nt150 C-CT was found. Also, there was no significant difference in the number of mutations between patients with different ages and different types of AL (AML, B-ALL). It is concluded that there is high frequency of mutations in the mtDNA D-loop, and the mutations may be associated with the pathogenesis of AL.
Assuntos
DNA Mitocondrial/genética , Leucemia/genética , Mutação , Adolescente , Adulto , Idoso , Células da Medula Óssea , Criança , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To describe the prevalence and risk factors for suicide ideation among college students in Chongqing city. METHODS: Data on suicide ideation and related factors were collected from 9808 college students at 11 colleges randomly selected in Chongqing. A multiple logistic regression model was used to identify risk factors for suicide ideation. RESULTS: 1279 (13.0%) of the 9808 students reported suicide ideation and the constituent ratio of boys and girls was 3:4 while risk factors for suicide ideation were ranked as follows: high frequency of feeling hopeless in prior year (OR = 5.07, 95%CI: 4.27 - 6.02); having psychological problems in recent 1 month that affecting daily lives and learning (2.07, 1.79 - 2.38); relatives having suicide behavior (1.77, 1.52 - 2.08); having had sexual experience (1.95, 1.65 - 2.30); being female (1.66, 1.45 - 1.90) and friends who had had suicide attempts (1.46, 1.28 - 1.67); having diseases in the last 1 month that affecting daily lives and learning (1.29, 1.08 - 1.52). CONCLUSION: The prevalence of suicide ideation among these college students was high that calls the development, implementation and assessment of suicide prevention plans for college students that focusing on the risk factors identified for suicide ideation.
Assuntos
Estudantes/psicologia , Ideação Suicida , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Fatores de Risco , Tentativa de Suicídio/psicologia , Inquéritos e Questionários , UniversidadesRESUMO
The study was purposed to explore the expressions of pituitary tumor transforming gene and c-myc gene in patients with multiple myeloma (MM) and its relationship with pathogenesis of MM. Expressions of pituitary tumor transforming gene and c-myc gene mRNA in BMMNC from 33 patients with MM and 10 normal controls were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the expressions of pituitary tumor transforming gene and c-myc gene mRNA were significantly higher in MM patients those that in normal controls (p<0.05). The expression of pituitary tumor transforming gene mRNA was significantly correlated with the expression of c-myc gene (r=0.801, p<0.05). In conclusion, the overexpressions of pituitary tumor transforming gene and c-myc gene may be related to the pathogenesis and progression of MM.
Assuntos
Mieloma Múltiplo/genética , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Securina , Adulto JovemRESUMO
OBJECTIVE: To investigated the related factors which affecting the severity degrees of post-traumatic stress disorder (PTSD) in transferred casualty after Wenchuan Earthquake. METHODS: Taking PTSD symptoms self-assessment scale (PCL-C) to involve 386 wounded who suffered 40 days after the earthquake disaster, from 11 hospitals and were transferred to Chongqing city. Multi-stage cluster sampling method was used. 354 valid questionnaires were recovered to explore the relevant factors affecting the severity on the symptoms of PTSD. RESULTS: This survey contains 354 subjects, with male 154 (43.6%), female 200 (56.4%), age 43.76 +/- 21.22, nation alities: Han people 236 (66.7%), Qiang people 114 (32.2%), others 4 (1.1%), and marriage status as unmarried 92 (26.1%), married 253 (71.7%), others 9 (2.2%). The wounded women PTSD have more serious symptoms than men, and there were differences between them in repeated and disturbing dreams of this stressful experience (t = 2.46, P = 0.014), a strong sense of psychological suffering annoyance (t = 2.02, P = 0.044), having difficulty concentrating (t = 2.04, P = 0.042), being "super-alert" (t = 2.465, P = 0.014) etc, also in the total scores (t = 2.489, P = 0.013) (P < 0.05). The PTSD symptoms of wounded degree in who had been buried in Earthquake were more serious than those not been buried. There were significant differences between them in the items as: avoid thinking about or talking about a stressful experience (t = 2.661, P = 0.008), avoid activities or situations that could recall the stressful experience (t = 2.705, P = 0.007), trouble remembering important parts of a stressful experience (t = 2.775, P = 0.006), feeling emotionally numb or being unable to have loving feelings for those close to you (t = 3.017, P = 0.003), feeling as if your future will somehow be cut short (t = 2.979, P = 0.003) and total scores (t = 3.175, P = 0.002). The wounded that witnessed someone be buried or died in earthquake, in PTSD symptoms, were more serious than those without. In the items of feeling distant or cut off from other people, feeling emotionally numb or being unable to have loving feelings for those close to you, feeling irritable or having angry outbursts, there were significant difference (P < 0.05 - 0.01). There were significant differences among the average score of the three core symptoms (F = 3.350, P < 0.001), among the three core symptoms as well as between the three core symptoms and total score respectively. CONCLUSION: There were differences in the severity degrees of PTST in transferred casualty under different exposed conditions. Correlations were also found between each of the symptoms.