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OBJECTIVE: To observe the effects of moxibustion on "Shenshu" and "Zusanli" on macrophage polarization and IL-4/STAT6 signaling pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA. METHODS: The rats' right hind paws were injected with freund's complete adjuvant (FCA) to establish the model of RA. Seven days after the injection of FCA, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. The researchers measured the thickness of the foot pad. ELISA and Histological Analysis were performed to observe the anti-inflammatory effect of moxibustion. Then researchers detected the expression of macrophage phenotype and the expression of IL-4/STAT6 signaling pathway related molecules. RESULTS: It was observed that after the injection of FCA, the rats' feet showed obvious symptoms of redness and swelling. But the symptoms were significantly improved when moxibustion was employed. The study found lower IL-23 and higher IL-4 level in the serum of FCA-injected rats after moxibustion treatment. HE staining showed that the synovium of the RA group was hyperemia and edema, with a large number of inflammatory cells infiltration and vascular dilatation. In the moxibustion group, the degree of synovial hyperemia and edema was improved, and the infiltration of inflammatory cells and vascular dilation were reduced. The study also found that there wer differences among the expressions of macrophage phenotypes in RA, and this was shown by the high expression of CD86 and low expression of CD206. However, the polarization of macrophages in the moxibustion group changed, and that was manifested by enhanced M2-polarized Mφs and inhibited M1-polarized Mφs. Meanwhile, moxibustion suppressed the activation of JAK1, JAK3 and STAT6 in the IL-4/STAT6 signaling pathway, which contributed to the polarization of M2 . CONCLUSION: The results demonstrate that moxibustion not only suppresses the polarization of M1, but also promotes the polarization of M1. The anti-inflammatory effect of moxibustion may be related to the regulation of macrophage polarization through IL-4/STAT6 signaling pathway.
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Artrite Reumatoide , Interleucina-4 , Macrófagos , Moxibustão , Fator de Transcrição STAT6 , Animais , Anti-Inflamatórios , Artrite Reumatoide/genética , Artrite Reumatoide/terapia , Polaridade Celular/genética , Polaridade Celular/fisiologia , Hiperemia , Interleucina-4/metabolismo , Macrófagos/metabolismo , Ratos , Fator de Transcrição STAT6/metabolismoRESUMO
Obesity is a growing chronic health problem worldwide. Studies about acupuncture for obesity treatment are many. But there are some doubts about the effectiveness of acupuncture versus sham acupuncture in treating obesity due to its lack of medical evidence. Therefore, the aim of this study is to assess the efficacy of acupuncture for obesity treatment and provide clinic evidence. Four English databases (PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials) and four Chinese databases (China National Knowledge Infrastructure, Chinese BioMedical Database, Chinese Scientific Journal Database and Wan-Fang Data) were searched from their receptions to August 2019. Randomized controlled trials (RCTs) using the comparison between acupuncture and sham acupuncture to treat simple obesity were included. The primary outcome of body mass index (BMI) would be used to measure the effect of acupuncture on obesity. According to the trial data extraction form based on the Cochrane Handbook, two reviewers separately extracted the data. Risk of bias of the RCTs was assessed by the Cochrane Risk of Bias Tool. The study included 8 RCTs with 403 patients. When compared with sham acupuncture, acupuncture showed obviously effect in BMI reduction (MD=1.0kg/m2, 95% CI=0.6 to 1.4, P<0.001). There was also significant reduction in body weight (MD=1.85kg, 95%CI=0.82 to 2.88, p<0.001), WC (MD=0.97cm, 95%CI=0.24 to 1.71, p=0.01) and body fat mass percentage (MD=1.01, 95%CI=0.25 to 1.77, p<0.05). However, WHR (MD=0.01, 95%CI=0 to 0.03, p>0.05) was not statistically and significantly different between the acupuncture and control groups. Adverse effects were reported in 3 studies. The review suggests that acupuncture is an effective therapy for simple obesity rather than a placebo effect. This potential benefit needs to be further evaluated by longer-term and more rigorous RCTs.
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Terapia por Acupuntura/métodos , Obesidade , Placebos , Índice de Massa Corporal , Humanos , Obesidade/psicologia , Obesidade/terapia , Resultado do TratamentoRESUMO
A one-pot novel strategy is described for the construction of various oxazolo[4,5-c]quinoline derivatives starting from the isocyano(triphenylphosphoranylidene)acetates, aldehydes, amines, and 2-azidobenzoic acids. The reactions generated the target products directly in moderate to good yields via a sequential Ugi/Wittig/aza-Wittig cyclization process. The salient features of the method are that all three groups of the multifunctional isocyanides were involved in the reaction with broad substituent scopes and mild reaction conditions, making the protocol a useful contribution to the synthesis of oxazolo[4,5-c]quinoline heterocycles.
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A robust ligand-free palladium-catalyzed cascade reaction for the synthesis of diversely substituted iminoisoindolinones has been developed. The cascade reaction involves isocyanide insertion into Ugi-3CR adducts, accompanied by unexpected hydroxylation and rearrangement.
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Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The ß of bendamustine-related AEs suggested risk reduction over time. Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.
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The past decade of studies showed that parenting behaviors (e.g., warmth, autonomy, and control) were associated with children's executive functions (EF) in the early years. However, different measurement methods had been used across studies, making it hard to compare the effects of parenting on EF across studies. Therefore, the present study aimed to examine the effect of the measurement methods on the relationship between maternal parenting behaviors and children's EF among a group of Chinese preschoolers. One hundred and twenty-six children (62 boys; Mage = 48.65 months) were assessed with direct measures on children's EF (inhibition and working memory tasks), and parenting behaviors of their mothers during interaction with children were observed and coded. Mothers also reported their parenting practices and children's difficulties in executive functions. The results of structural equation modeling showed that the latent performance-based EF was uniquely predicted by maternal positive control and negative control in mother-child interaction, while children's EF difficulties reported by mothers were predicted by mother-reported warmth and support, and autonomy granting. Overall, the results suggest that the relationship between maternal parenting and children's EF depends on the measurement methods of parenting and executive functions.
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OBJECTIVE: This study aimed to investigate the long-term effects of early stress by Tangshan earthquake on symptoms of depression in adulthood. METHOD: A total of 1534 volunteers born and raised in Tangshan were investigated; finally, 1328 subjects were enrolled in the study. They were divided into three groups according to their birth dates: infant exposure, prenatal exposure, and non-exposure. The questionnaires and psychological evaluation of all subjects were completed using a one-on-one psychological test. RESULTS: The rate of depressive symptoms in the prenatal exposure group was the highest, and the lowest in the non-exposure group, with statistical differences among the three groups (P = 0.002). Moreover, the incidences of depressed mood, suicide ideation and work and loss of interest in the prenatal exposure group were significantly higher than those in the infant exposure group and the non-exposure group (P = 0.008, P = 0.001, P = 0.038, respectively). Multiple logistic regression analysis showed that male could be a protective factor for symptoms of depression in adulthood, and earthquake exposure was an important predictor of the incidence of depression symptoms. CONCLUSIONS: Fetal or infancy exposure to earthquake might correlate to depression symptoms in adulthood.
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Terremotos , Efeitos Tardios da Exposição Pré-Natal , Transtornos de Estresse Pós-Traumáticos , Gravidez , Feminino , Humanos , Masculino , Adulto , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , China/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: In China, the identification rate and treatment rate of mental disorders are low, and there are few surveys on the prevalence of mental disorders among college students using diagnostic tools such as Mini-International Neuropsychiatric Interview (MINI), so the prevalence and treatment of mental disorders among college students are unclear. AIM: To estimate prevalence of mental disorders among medical students in Hebei Province, and provide guidance for improving their mental health. METHODS: This was a cross-sectional study based on an Internet-based survey. Three levels of medical students in Hebei Province were randomly selected (by cluster sampling) for screening. Using the information network assessment system, the subjects scanned the 2D code with their mobile phones, clicked to sign the informed consent, and answered a scale. A self-designed general status questionnaire was used to collect information about age, gender, ethnicity, grade, and origin of students. The MINI 5.0. was used to investigate mental disorders. Data analysis was performed with SPSS software. Statistically significant findings were determined using a two-tailed P value of 0.05. RESULTS: A total of 7117 subjects completed the survey between October 11 and November 7, 2021. The estimated prevalence of any mental disorders within 12 mo was 7.4%. Mood disorders were the most common category (4.3%), followed by anxiety disorders (3.9%); 15.0% had been to psychological counseling, while only 5.7% had been to a psychiatric consultation, and only 10% had received drug therapy in the past 12 mo. CONCLUSION: Although the estimated prevalence of mental disorders in medical students is lower than in the general population, the rate of adequate treatment is low. We determined that improving the mental health of medical students is an urgent matter.
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BACKGROUND: The critical diagnostic criteria for esophagogastric junction outflow obstruction (EGJOO) were published in the latest Chicago Classification version 4.0 (CCv4.0). In addition to the previous criterion [elevated integrated relaxation pressure (IRP) in supine position], manometric diagnosis of EGJOO requires meeting the criteria of elevated median-IRP during upright wet swallows and elevated intrabolus pressure. However, with the diagnostic criteria modification, the change in manometric features of EGJOO remained unclear. AIM: To evaluate the esophageal motility characteristics of patients with EGJOO and select valuable parameters for confirming the diagnosis of EGJOO. METHODS: We performed a retrospective analysis of 370 patients who underwent high-resolution manometry with 5 mL water swallows × 10 in supine, × 5 in upright position and the rapid drink challenge (RDC) with 200 mL water from November 2016 to November 2021 at Peking University First Hospital. Fifty-one patients with elevated integrated supine IRP and evidence of peristalsis were enrolled, with 24 patients meeting the updated manometric EGJOO diagnosis (CCv4.0) as the EGJOO group and 27 patients not meeting the updated EGJOO criteria as the isolated supine IRP elevated group (either normal median IRP in upright position or less than 20% of supine swallows with elevated IBP). Forty-six patients with normal manometric features were collected as the normal high-resolution manometry (HRM) group. Upper esophageal sphincter (UES), esophageal body, and lower esophageal sphincter (LES) parameters were compared between groups. RESULTS: Compared with the normal HRM group, patients with EGJOO (CCv4.0) had significantly lower proximal esophageal contractile integral (PECI) and proximal esophageal length (PEL), with elevated IRP on RDC (P < 0.05 for each comparison), while isolated supine IRP elevated patients had no such feature. Patients with EGJOO also had more significant abnormalities in the esophagogastric junction than isolated supine IRP elevated patients, including higher LES resting pressure (LESP), intrabolus pressure, median supine IRP, median upright IRP, and IRP on RDC (P < 0.05 for each comparison). Patients with dysphagia had significantly lower PECI and PEL than patients without dysphagia among the fifty-one with elevated supine IRP. Further multivariate analysis revealed that PEL, LESP, and IRP on RDC are factors associated with EGJOO. The receiver-operating characteristic analysis showed UES nadir pressure, PEL, PECI, LESP, and IRP on RDC are parameters supportive for confirming the diagnosis of EGJOO. CONCLUSION: Based on CCv4.0, patients with EGJOO have more severe esophagogastric junction dysfunction and are implicated in the proximal esophagus. Additionally, several parameters are supportive for confirming the diagnosis of EGJOO.
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Transtornos de Deglutição , Transtornos da Motilidade Esofágica , Gastropatias , Transtornos da Motilidade Esofágica/complicações , Esfíncter Esofágico Inferior , Junção Esofagogástrica , Humanos , Manometria , Estudos Retrospectivos , Gastropatias/complicações , ÁguaRESUMO
BACKGROUND: This study aims to systematically evaluate the effect of moxibustion on the level of inflammatory cytokines in animal models with rheumatoid arthritis (RA) and to provide evidence for the clinical application of moxibustion to the treatment of RA and related basic researches. METHODS: The databases employed in this study include PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), SinoMed, and Wanfang Data Information Site. The retrieval time was from the establishment of these databases to March 2020. The reviewers made use of the CAMARADES 10-item checklist to evaluate the quality of each included study. The inflammatory cytokines were considered as the outcome measure. The Revman 5.3 software was used to conduct meta-analysis on the outcome indicators of the studies included. RESULTS: A total of 648 articles were retrieved and 18 animal experiments were included in this study. The quality scores of the studies ranged from two to eight with a mean of 5.8. Compared with the effect of the control group, moxibustion reduced the expression of TNF-α (SMD 2.95, 95% CI: 1.99-3.92, P < 0.00001), IL-1ß (SMD 4.10, 95% CI: 2.37-5.84, P < 0.00001), IFN-γ (MD 25, 95% CI: 16.17-33.82, P < 0.00001), IL-6 (MD 11.83, 95% CI: 6.22-17.44, P < 0.0001), and IL-17 (MD 99.3, 95% CI: 86.83-111.76, P < 0.00001). At the same time, the level of IL-2 (SMD 8.89, 95% CI: 0.93-16.86, P=0.03), IL-4 (MD 1.79, 95% CI: 0.26-3.32, P=0.02), and IL-10 (MD 5.93, 95% CI: 1.37-10.49, P=0.01) increased after moxibustion treatment. Asymmetric funnel plots indicated that there was publication bias. CONCLUSION: The findings of the present review indicate that moxibustion can protect the synovium of joint in animal models with RA by upregulation of the level of anti-inflammatory cytokines and downregulation of the level of proinflammatory cytokines. Moxibustion has the potential to relieve inflammation of RA.
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The objective of the current study was to determine whether exposure to earthquake stress during pregnancy and infancy impacted on the risk of chronic adult health problems. All subjects were divided into three groups: the infant exposure group, the fetus exposure group, and the non-exposure group. All subjects completed a standardized interview that included questions on demographic information, traumatic experiences during the earthquake, Anthropomorphic parameters such as body height, weight, and blood pressure were measured. Traumatic events in childhood and adulthood were assessed by the Childhood Trauma Questionnaire (CTQ) and Life Event Scale (LES), respectively. Totally1325 subjects were included; 399 subjects experienced the earthquake as fetuses, 374 subjects who experienced the earthquake as infants and 552 subjects did not experience the earthquake. The three groups were comparable in sociodemographic and baseline characteristics except age (Infant exposure vs Prenatal exposure vs No exposure = 39.5 ± 0.6 vs 38.5 ± 0.8 vs 37.5 ± 0.9, p < .001). Fetal and infant exposure to earthquakes was associated with elevated systolic blood pressure (both were + 3 mm Hg, p < .001). After adjustment for covariates, earthquake exposure in infants (odds ratio [OR] = 2.010, 95% confidence interval [CI] = 1.216 ~ 3.322) and fetuses (OR = 1.509, 95% CI = 1.014 ~ 2.248) was a significant and independent risk factor for hypertension. Earthquake expose in fetuses was a significant and independent risk factor for diabetes (OR = 2.307, 95% CI = 1.136 ~ 4.686). Earthquake exposure in infants and fetuses is a significant and independent risk factor for hypertension. Earthquake exposure in fetuses is significant and independent risk factor for diabetes.
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Diabetes Mellitus , Terremotos , Hipertensão , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Gravidez , Fatores de RiscoRESUMO
OBJECTIVE: To systematically review the effects of moxibustion on serum cytokines in experimental animals with rheumatoid arthritis. METHODS: PubMed, Embase, Web of Science, The Cochrane Library, CNKI, VIP, Wanfang Data, and CBM were searched for animal experiments on moxibustion intervention for rheumatoid arthritis. Related data were extracted, and RevMan 5.3 was used to perform a meta-analysis of outcome measures, including serum tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), interleukin-17 (IL-17), interleukin-2 (IL-2), interferon-γ (IFN-γ), receptor activator of nuclear factor-kappa B ligand (RANKL), transforming growth factor-ß (TGF-ß), and degree of swelling of diseased joint. RESULTS: A total of 18 studies were included. The detection methods included radioimmunoassay and ELISA and the experimental animal species included rats and rabbits. The studies on serum TNF-α and degree of swelling of diseased joint had publication bias. Meta-analysis showed that the moxibustion group had significant reductions in the serum levels of TNF-α, IL-1, IL-2, IL-6, VEGF, IL-17, and RANKL, significant increases in the serum levels of TGF-ß and IFN-γ, and a significant reduction in the degree of swelling of diseased joints in model animals. CONCLUSION: Moxibustion can effectively regulate levels of the serum cytokines in experimental animals of rheumatoid arthritis and thus reduce inflammatory response and alleviate the swelling of diseased joints.
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Artrite Experimental , Artrite Reumatoide , Moxibustão , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/terapia , Citocinas/genética , Coelhos , Ratos , Fator de Necrose Tumoral alfa , Fator A de Crescimento do Endotélio VascularRESUMO
Low expression levels of CREBbinding protein (CREBBP) have been demonstrated to be associated with high minimal residual disease at the end of induction therapy and adverse longterm outcomes in pediatric patients with acute lymphoblastic leukemia (ALL). However, the effect of low CREBBP expression on the prognosis of ALL has not yet been investigated. In the present study, CREBBP was downregulated and overexpressed in ALL cell lines (Jurkat and Reh). Sensitivity to chemotherapy and cell proliferation activity was determined via a Cell Counting Kit8 assay. Cell cycle analysis was performed using flow cytometry. Immunofluorescence confocal microscopy and coimmunoprecipitation (CoIP) assays were performed to determine the interaction between CREBBP and E2F transcription factor 3a (E2F3a). The binding of CREBBP to downstream gene caspase 8 associated protein 2 (CASP8AP2) promoters was assessed using a chromatin immunoprecipitation assay, and mRNA expression levels were detected via reverse transcriptionquantitative PCR. Western blot analysis was performed to detect protein expression of CREBBP, E2F3a and CASP8AP2. Downregulation of CREBBP increased the IC50 value of daunorubicin; however, no significant affects were observed on the IC50 values of vincristine and Lasparaginase. Furthermore, downregulation of CREBBP notably inhibited leukemia cell proliferation, accumulated cells in the G0/G1 phase and decreased cell proportions in the S and G2/M phases. CoIP analysis demonstrated that CREBBP interacted with E2F3a, a transcription factor involved in G1/S transition. Immunofluorescence confocal microscopy indicated colocalization of CREBBP and E2F3a at the cell nucleus. Furthermore, E2F3a protein expression decreased in CREBBP RNA interference treated Jurkat and Reh cells. CASP8AP2, a target gene of E2F3a, was also identified to be a downstream gene of CREBBP. In addition, decreased IC50 value and cell proportions in the G0/G1 phase, accelerated cell proliferation and upregulated E2F3a and CASP8AP2 expression were exhibited in CREBBP overexpressed cells. Taken together, the results of the present study suggested that CREBBP downregulation affects proliferation and cell cycle progression in leukemia cells, potentially via the interaction and regulation of E2F3a, resulting in chemotherapy resistance. Thus, targeting CREBBP may be a therapeutic strategy for treating pediatric patients with ALL.
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Antibióticos Antineoplásicos/farmacologia , Proteína de Ligação a CREB/metabolismo , Pontos de Checagem do Ciclo Celular/genética , Proliferação de Células/genética , Daunorrubicina/farmacologia , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteína de Ligação a CREB/genética , Proteínas de Ligação ao Cálcio/metabolismo , Núcleo Celular/metabolismo , Fator de Transcrição E2F3/metabolismo , Humanos , Concentração Inibidora 50 , Células Jurkat , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Interferência de RNA , Transdução de Sinais/genética , TransfecçãoRESUMO
BACKGROUND: Obesity is a growing chronic health problem worldwide. Studies about acupuncture for obesity treatment are many. But there are some doubts about the effectiveness of acupuncture vs sham acupuncture in treating obesity due to its lack of an evidence-based medical proof. Therefore, the aim of this study is to assess the efficacy of acupuncture for obesity treatment and provide clinic evidence. METHODS: This protocol was based on the previous reporting items for systematic review and meta-analysis agreements. Four English databases (PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials) and 4 Chinese databases (China National Knowledge Infrastructure, Chinese BioMedical Database, Chinese Scientific Journal Database, Wan-Fang Data) will be searched from their receptions to August 2019. Randomized controlled trials (RCTs) using acupuncture compared sham acupuncture (or no treatment) to treat simple obesity will be included. The primary outcome of body mass index (BMI) and body weight (BW) will be used to measure the effect of acupuncture on obesity. According to the trial data extraction form based on the Cochrane Handbook, 2 reviewers will separately extract the data. Risk of bias of the RCTs will be assessed by the Cochrane Risk of Bias Tool. Publication bias will be assessed with funnel plots. RESULTS: This study will be to evaluate whether acupuncture is an effective intervention for simple obesity when compared with sham acupuncture. CONCLUSION: The conclusion of this study will help clinicians provide effective treatment options for obese patients. ETHICS AND DISSEMINATION: Ethical approval is not required for systematic review and meta- analysis. The results of this review will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019129825.
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Terapia por Acupuntura/métodos , Obesidade/terapia , Humanos , Resultado do Tratamento , Metanálise como AssuntoRESUMO
OBJECTIVE: To explore the effects of TBLR1-RARα on the differentiation induction of leukemia cell line K562 cells into erythroid lineage and to investigate its related mechanisms. METHODS: Tet-Off inducible system was used to construct the conditional expression vector of TBLR1-RARα fusion gene by cloning the TBLR1-RARα fragment into lentivirus vector pLVX-Tight-Puro, the expression of TBLR1-RARα fusion gene was induced by doxycycline (Dox). Then, K562 cells were transfected with lentivirus pLVX-Tight-Puro-TBLR1-RARα-flag, and the expression of fusion proteins was verified by Western blot. After treatment of K562 with all-trans retinoid acid (ATRA), real time RT-PCR was performed to test the expression of erythroid differentiation-related CD71 and α, ε, γ-globins gene. Flow cytometry was used also to analyze the expression of erythroid differentiation markers CD71 and CD235a. Benzidine staining was used to detect the production of hemoglobin in K562 cells. RESULTS: qRT-RCR showed that ATRA could increase the expression level of CD71 and α, ε, γ-globin genes when TBLR1-RARα was expressed. After treatment of ATRA, the proportion of CD71(+) cells detected by the flow cytometry also increased. Benzidine staining showed that ATRA could induce hemoglobin production in K562 cells with TBLR1-RARα fusion gene expression. CONCLUSION: The expression of TBLR1-RARα fusion gene contribute to ATRA-inducing differentiation of K562 cells into erythroid lineage.
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Diferenciação Celular , Eritrócitos , Hemoglobinas , Humanos , Células K562 , Proteínas Nucleares , Receptores Citoplasmáticos e Nucleares , Receptores do Ácido Retinoico , Proteínas Repressoras , Receptor alfa de Ácido Retinoico , gama-GlobinasRESUMO
Baicalin, a flavonoid monomer derived from Scutellaria baicalensis called Huangqin in mandarin, is the main active ingredient contributing to S. baicalensis' efficacy. It is known in China that baicalin has potential therapeutic effects on inflammatory diseases. However, its anti-inflammatory mechanism has still not been fully interpreted. We aim to investigate the anti-inflammatory effect of baicalin on lipopolysaccharide (LPS)-induced inflammation in HBE16 airway epithelial cells and also to explore the underlying signaling mechanisms. The anti-inflammatory action of baicalin was evaluated in human airway epithelial cells HBE16 treated with LPS. Airway epithelial cells HBE16 were pretreated with a range of concentrations of baicalin for 30 min and then stimulated with 10 µg/ml LPS. The secretions of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in cell culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of IL-6, IL-8, and TNF-α were tested by quantitative real-time polymerase chain reaction (real-time RT-PCR). Furthermore, Western blotting was used to determine whether the signaling pathway NF-κB was involved in the anti-inflammatory action of baicalin. The inflammatory cell model was successfully built with 10 µg/ml LPS for 24 h in our in vitro experiments. Both the secretions and the mRNA expressions of IL-6, IL-8, and TNF-α were significantly inhibited by baicalin. Moreover, the expression levels of phospho-IKKα/ß and phospho-NF-κB p65 were downregulated, and the phospho-IκB-α level was upregulated by baicalin. These findings suggest that the anti-inflammatory properties of baicalin may be resulted from the inhibition of IL-6, IL-8, and TNF-α expression via preventing signaling NF-κB pathway in HBE16 airway epithelial cells. In addition, this study provides evidence to understand the therapeutic effects of baicalin on inflammatory diseases in clinical practice.
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Flavonoides/farmacologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Mucosa Respiratória/metabolismo , Scutellaria , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/prevenção & controle , Mediadores da Inflamação/antagonistas & inibidores , Lipopolissacarídeos/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Mucosa Respiratória/citologia , Mucosa Respiratória/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
A facile synthesis of highly substituted 4-sulfonyl-1H-pyrazoles from N-propargylic sulfonylhydrazone derivatives has been developed. Allenic sulfonamide formation and 1,3-sulfonyl shift were established to be the critical steps of this transformation.
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Hidrazonas/química , Bases de Lewis/química , Pirazóis/síntese química , Catálise , Estrutura Molecular , Pirazóis/químicaRESUMO
OBJECTIVE: It is necessary to compensate the system latencies in real-time tumor-tracking radiotherapy by prediction. However, due to the irregularities of respiratory motions, the results obtained with traditional methods were not acceptable. The purpose of this study is to evaluate the value of nonparametric regression model in respiratory motion prediction. METHODS: The data of respiratory trajectory of 11 volunteers were obtained and predicted based on nonparametric regression method. The results were compared with those of autoregressive model and back propagation neural network. An improved method was proposed to deal with the abnormal state in respiration. We combined the prediction method with the tracking system to test its performance in practical application. RESULTS: The results indicated that the proposed method could predict the motion accurately in real-time for different latencies. This method decreased the error of the abnormal state substantially and also allowed effective prediction of respiration motion when combined with the tracking system. CONCLUSION: The nonparametric regression model can predict the respiratory motion accurately in real-time and therefore meets the requirement of real-time tumor-tracking radiotherapy.
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Modelos Teóricos , Radioterapia Assistida por Computador/métodos , Respiração , Previsões , Humanos , Movimento , Neoplasias/radioterapia , Análise de RegressãoRESUMO
OBJECTIVE: To validate the efficiency and accuracy of an improved Demons deformable registration algorithm and evaluate its application in contour recontouring in 4D-CT. METHODS: To increase the additional Demons force and reallocate the bilateral forces to accelerate convergent speed, we propose a novel energy function as the similarity measure, and utilize a BFGS method for optimization to avoid specifying the numbers of iteration. Mathematical transformed deformable CT images and home-made deformable phantom were used to validate the accuracy of the improved algorithm, and its effectiveness for contour recontouring was tested. RESULTS: The improved algorithm showed a relatively high registration accuracy and speed when compared with the classic Demons algorithm and optical flow based method. Visual inspection of the positions and shapes of the deformed contours agreed well with the physician-drawn contours. CONCLUSION: Deformable registration is a key technique in 4D-CT, and this improved Demons algorithm for contour recontouring can significantly reduce the workload of the physicians. The registration accuracy of this method proves to be sufficient for clinical needs.