RESUMO
OBJECT: To evaluate the efficacy of dydrogesterone for the treatment of premenopausal patients with endometrial polyps (EPs). METHODS: A single-center, open-label, prospective, single-arm clinical treatment trial was conducted in patients of reproductive age with EP(s). Patients were prescribed dydrogesterone from day 15 to day 24 of the menstrual cycle over a period of 3 months. At the 3-month follow-up, the efficacy of dydrogesterone was evaluated based on changes in self-report symptoms and ultrasonographic characteristics. The predictive factors of efficacy as well as the predictive value of the significant factors were also assessed. RESULTS: A total of 60 patients were included. Improvements in both symptoms and ultrasound findings occurred in 31 patients, achieving an efficacy rate of 51.67%. Of 41 patients with clinical presentations, 39 (95.1%) reported improvements in symptoms. In terms of ultrasound findings, 33 (55%) of patients demonstrated improvements. Significant decreases were observed in the mean endometrial thickness (1.17 ± 0.33 cm vs 0.90 ± 0.35 cm, p < .001) and polyp size (1.10 ± 0.34 cm vs 0.74 ± 0.65 cm, p = .001) after the application of dydrogesterone. Age (p = .006), polyp size (p = .006), and blood flow within polyps (p = .035) were significant predictors of dydrogesterone efficacy. These factors, when combined, demonstrated a good predictive value ([area under the curve (AUC)=0.81]). CONCLUSION: Dydrogesterone is effective in the management of EPs in premenopausal patients. Age, polyp size and blood flow should be taken into consideration when prescribing dydrogesterone for this population of women.
Assuntos
Didrogesterona/uso terapêutico , Pólipos/tratamento farmacológico , Progestinas/uso terapêutico , Doenças Uterinas/tratamento farmacológico , Adulto , Feminino , Humanos , Pré-Menopausa , Estudos Prospectivos , Ultrassonografia , Doenças Uterinas/diagnóstico por imagemRESUMO
BACKGROUND: Arthroscopic repair is recommended for young patients with full-thickness rotator cuff tears (RCTs), but the healing rates have raised concerns. The Southern California Orthopedic Institute (SCOI) row method has been developed based on greater than 3 decades of experience with excellent clinical outcomes; however, studies with a focus on the younger patient population are limited in number. The current study assessed the short-term clinical outcome and the initial tendon-to-bone healing in a young cohort after repair of a full-thickness RCT using the SCOI row method. METHODS: A retrospective cohort study was performed. Patients < 55 years of age who had a full-thickness RCT and underwent an arthroscopic repair using the SCOI row method were reviewed. Clinical outcomes were assessed at baseline, and 3 and 6 months post-operatively. The visual analog scale (VAS), University of California at Los Angeles (UCLA) scale, and Constant-Murley score were completed to assess pain and function. Active range of motion was also examined, including abduction and flexion of the involved shoulder. A preoperative MRI was obtained to assess the condition of the torn tendon, while 3- and 6-month postoperative MRIs were obtained to assess tendon-to-bone healing. Repeated measurement ANOVA and chi-square tests were used as indicated. RESULTS: Eighty-nine patients (57 males and 32 females) with a mean age of 44.1 ± 8.6 years who met the criteria were included in the study. Compared with baseline, clinical outcomes were significantly improved 3 and 6 months postoperatively based on improvement in the VAS, UCLA score, and Constant-Murley score, as well as range of motion. Greater improvement was also noted at the 6-month postoperative assessment compared to the 3-month postoperative assessment. Three- and six-month postoperative MRIs demonstrated intact repairs in all shoulders and footprint regeneration, which supported satisfactory tendon-to-bone healing. The mean thickness of regeneration tissue was 7.35 ± 0.76 and 7.75 ± 0.79 mm as measured from the 3- and 6-month MRI (P = 0.002). The total satisfactory rate was 93.3 %. CONCLUSIONS: Arthroscopic primary rotator cuff repair of a full-thickness RCT using the SCOI row method in patients < 55 years of age yields favorable clinical outcomes and early footprint regeneration.
Assuntos
Lesões do Manguito Rotador , Adulto , Artroscopia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Tendões , Resultado do TratamentoRESUMO
OBJECTIVES: Since other genital infections enhance HIV susceptibility by inducing inflammation and evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of high-risk human papillomavirus (HPV) infections, we investigated the relationship between the composition of the vaginal microbiota and the risk of high-risk HPV infection. METHODS: The study included 151 healthy women (65 HPV-positive and 86 HPV-negative) aged 20-65 at enrollment. Total genome DNA from samples was extracted using the hexadecyltrimethylammonium bromide (CTAB) CTAB method. The vaginal microbiota composition was determined by sequencing barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. RESULTS: Of the 30 most abundant bacteria at the genus level, we found only six bacteria with a statistical difference between HPV-positive and HPV-negative women: Bacteroides, Acinetobacter, Faecalibacterium, Streptococcus, Finegoldia, and Moryella. Lactobacillus was the predominant genus and was detected in all women, but there was no significant difference between the two groups for L. iners, L. jensenii, and L. gasseri. Furthermore, we found 26 types of bacteria with a statistical difference at the species level between the two groups. Anaerobic bacteria such as Bacteroides plebeius, Acinetobacter lwoffii, and Prevotella buccae were found significantly more frequently in HPV-positive women, which is the most important finding of our study. CONCLUSION: Our findings suggest a possible role for the composition of the vaginal microbiota as a modifier of high-risk HPV infection, and specific microbiota species may serve as sensors for changes in the cervical microenvironment associated with high-risk HPV infection. The exact molecular mechanism of the vaginal microbiota in the course of high-risk HPV infection and cervical neoplasia should be further explored. Future research should include intervention in the composition of the vaginal microbiota to reverse the course of high-risk HPV infection and the natural history of cervical neoplasia.
Assuntos
Bactérias/classificação , Bactérias/isolamento & purificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/microbiologia , Vagina/microbiologia , Vagina/virologia , Adulto , Bactérias/genética , China/epidemiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Prognóstico , Fatores de Risco , Microambiente Tumoral , Adulto JovemRESUMO
In order to research how does hypomethylating agents ameliorate iron metabolism in myelodysplastic syndrome (MDS), we performed methylation-specific, polymerase chain reaction (MSP), bisulfate genomic sequencing polymerase chain reaction (BSP), quantitative real-time PCR and western blot of hemojuvelin (HJV) and ELISA assay for hepcidin before and after demethylating therapy (decitabine) to determine whether the change of HJV methylation status would have an influence on hepcidin expression. Eleven of 22 MDS patients achieved CR or PR according to IWG criteria (50%). HJV mRNA was induced in decitabine responders (p = .006 comparing pre/post decitabine treatment) but not in non-responders (p = .121). Similarly, hepcidin serum expression increased from 320.77 ± 34.8 µg/L to 366.77 ± 21.90 µg/L (p = .012) in responders but did not significantly change in non-responders (p = .058), while no difference of adjusted serum ferritin (ASF) was found. In conclusion, hypermethylation of HJV promoter region could silence the gene expression and demethylating therapy might ameliorate iron-overload through HJV demethylation.
Assuntos
Azacitidina/análogos & derivados , Metilases de Modificação do DNA/antagonistas & inibidores , Sobrecarga de Ferro/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Azacitidina/uso terapêutico , Proteína Morfogenética Óssea 2/fisiologia , Metilação de DNA , Decitabina , Feminino , Ferritinas/sangue , Proteínas Ligadas por GPI/genética , Proteína da Hemocromatose , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/metabolismoRESUMO
Our previous studies showed that atractylenolide II (AT-II) has antimelanoma effects in B16 melanoma cells. In this study, we investigated the involvement of STAT3 signalling in the antimelanoma action of AT-II. Daily administration of AT-II (12.5, 25 mg/kg, i.g.) for 14 days significantly inhibited tumor growth in a B16 xenograft mouse model and inhibited the activation/phosphorylation of STAT3 and Src in the xenografts. In B16 and A375 cells, AT-II (20, 40 µm) treatment for 48 h dose-dependently reduced protein expression levels of phospho-STAT3, phospho-Src, as well as STAT3-regulated Mcl-1 and Bcl-xL. Overexpression of a constitutively active variant of STAT3, STAT3C in A375 cells diminished the antiproliferative and apoptotic effects of AT-II. These data suggest that inhibition of STAT3 signalling contributes to the antimelanoma action of AT-II. Our findings shed new light on the mechanism of action underlying the antimelanoma effects of AT-II and provide further pharmacological basis for developing AT-II as a novel melanoma chemopreventive/chemotherapeutic agent.
Assuntos
Lactonas/química , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Fator de Transcrição STAT3/metabolismo , Sesquiterpenos/química , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Animais , Anticarcinógenos/química , Apoptose , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Melanoma Experimental , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/antagonistas & inibidores , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Masking the miRNA binding site: Crosslink-forming oligonucleotide (CFO) was used for target gene-specific inhibition of microRNA (miRNA) functions. This method can interfere with specific miRNA-mRNA interactions by recognizing sequences unique to the 3'-UTR that are inherent in each mRNA.
Assuntos
Reagentes de Ligações Cruzadas/farmacologia , Inativação Gênica/efeitos dos fármacos , MicroRNAs , Oligodesoxirribonucleotídeos/farmacologia , Purinas , RNA Mensageiro/química , Compostos de Vinila , Animais , Sequência de Bases , Sítios de Ligação/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Vaga-Lumes , Células HeLa , Humanos , Luciferases/química , Luciferases/genética , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos/química , RNA Mensageiro/metabolismoRESUMO
AIM: Epstein-Barr virus-associated intrahepatic cholangiocarcinoma (EBVaICC) has a distinct genomic profile and increased CD3+ and CD8+ T cells infiltration. However, the efficacy of immunotherapy in EBVaICC remains largely unknown. This study aimed to assess the efficacy of programmed cell death protein 1 (PD-1) antibody therapy in EBVaICC. METHODS: Patients with metastatic biliary tract cancer (BTC) diagnosed at Sun Yat-sen University Cancer Center from January 2016 to December 2021 were identified. In situ hybridisation was performed to detect EBV. Overall survival (OS) and progression-free survival (PFS) were measured. RESULTS: A total of 698 patients with metastatic BTC were identified, of whom 39 (5.6%) had EBVaICC. Among the 136 patients who were not administered PD-1 antibody, the OS was similar between patients with EBVaICC and EBV-negative ICC (median OS 12.5 versus 9.5 months, respectively; P = 0.692). For the 205 patients who were administered PD-1 antibody, patients with EBVaICC had significantly longer OS than patients with EBV-negative ICC (median OS 24.9 versus 11.9 months, respectively; P = 0.004). Seventeen patients with EBVaICC were administered PD-1 antibody. Eight patients (47%) achieved a partial response, and 17 patients achieved disease control. The median PFS was 17.5 months. CONCLUSIONS: This study identified a clinically actionable subset of patients with EBVaICC with a promising response to the PD-1 antibody.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Infecções por Vírus Epstein-Barr , Humanos , Herpesvirus Humano 4 , Infecções por Vírus Epstein-Barr/complicações , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Colangiocarcinoma/patologia , Neoplasias dos Ductos Biliares/patologia , Imunoglobulinas , Ductos Biliares Intra-Hepáticos/patologiaRESUMO
The development of convenient methods for controlling the protein expression is an important challenge in the postgenomic era. We applied the crosslink forming oligonucleotide (CFO) as a terminator of the ribosomal translation. In this study, we demonstrated that the improved reactivity of our CFO under physiological conditions enabled the sequence-specific introduction of a steric block for a ribosome on mRNAs. In vitro and in cell translation experiments revealed that the crosslinked mRNA can produce the truncated proteins in which the translation terminates at the desired position.
Assuntos
Oligorribonucleotídeos/genética , Terminação Traducional da Cadeia Peptídica/genética , Biossíntese de Proteínas , Purinas/metabolismo , RNA Mensageiro/genética , Compostos de Vinila/metabolismo , Sequência de Bases , Dados de Sequência Molecular , Oligorribonucleotídeos/metabolismo , Engenharia de Proteínas , Purinas/química , RNA Mensageiro/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Compostos de Vinila/químicaRESUMO
BACKGROUND: Although excellent clinical outcomes of supercapsular percutaneously assisted total hip arthroplasty (SuperPath) have been reported, the peri-operative blood loss has rarely been reported. The current study determined the blood loss during SuperPath and compared the blood loss with conventional posterolateral total hip arthroplasty (PLTH). METHODS: This retrospective study enrolled patients who underwent unilateral primary THA between January 2017 and December 2019. The demographic data, diagnoses, affected side, radiographic findings, hemoglobin concentration, hematocrit, operative time, transfusion requirements, and intra-operative blood loss were recorded. The peri-operative blood loss was calculated using the OSTHEO formula. Blood loss on the 1st, 3rd, and 5th post-operative days was calculated. Hidden blood loss (HBL) was determined by subtracting the intra-operative blood loss from the total blood loss. RESULTS: Two hundred sixty-three patients were included in the study, 85 of whom were in the SuperPath group and 178 in the posterolateral total hip arthroplasty (PLTH) group. Patient demographics, diagnoses, affected side, operative times, and pre-operative hemoglobin concentrations did not differ significantly between the two groups (all P > 0.05). Compared to the PLTH group, the SuperPath group had less blood loss, including intra-operative blood loss, 1st, 3rd, and 5th post-operative days blood loss, and HBL (all P < 0.05). Total blood loss and HBL was 790.07 ± 233.37 and 560.67 ± 195.54 mL for the SuperPath group, respectively, and 1141.26 ± 482.52 and 783.45 ± 379.24 mL for the PLTH group. PLTH led to a greater reduction in the post-operative hematocrit than SuperPath (P < 0.001). A much lower transfusion rate (P = 0.028) and transfusion volume (P = 0.019) was also noted in the SuperPath group. CONCLUSION: SuperPath resulted in less perioperative blood loss and a lower transfusion rate than conventional PLTH.
Assuntos
Artroplastia de Quadril/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Transfusão de Sangue/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Glutamate is an excitatory neurotransmitter that plays a major role in the pathogenesis of ischemia brain injury. The regulation of glutamate neurotransmission is carried out by excitatory amino acid transporters (EAATs) that act through reuptake of glutamate into cells. EAATs may also release glutamate into the extracellular space in a calcium-independent manner during ischemia and dysfunction of EAATs is specifically implicated in the pathology of cerebral ischemia. Recent studies show that up-regulation of EAAT2 provides neuroprotection during ischemic insult. This review summarizes current knowledge regarding the role of EAATs in cerebral ischemia.
Assuntos
Isquemia Encefálica/metabolismo , Proteínas de Transporte de Glutamato da Membrana Plasmática/fisiologia , Animais , Regulação da Expressão Gênica , Proteínas de Transporte de Glutamato da Membrana Plasmática/biossíntese , HumanosRESUMO
OBJECTIVE: To explore the risk factors for the recurrence of endometrioma and the risk factors for the recurrence of endometriosis-related pain after long-term follow-up. METHODS: This study retrospectively analyzed 358 women with endometriomas who had a minimum of 5-years follow up after laparoscopic endometrioma excision, which was performed at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into recurrence group and nonrecurrence group. Analysis was performed with regard to preoperative history, laboratory analysis, findings during surgery, and symptoms during follow-up, including improvement and recurrence. RESULTS: The cumulative incidence rates of recurrence from 5 to 10 years after surgery were 15.4, 16.8, 19.3, 22.5, 22.5, and 22.5%, respectively. Significant differences were found between two groups in terms of age at surgery (RR: 0.764, 95% CI: 0.615-0.949, p = 0.015), duration of dysmenorrhea (RR: 1.120, 95% CI: 1.054-1.190, p < 0.001), presence of adenomyosis (RR: 1.629, 95% CI: 1.008-2.630, p = 0.046), CA125 level (RR: 1.856, 95% CI: 1.072-3.214, p = 0.021) and severity of dysmenorrhea. The severity of dysmenorrhea (RR: 1.711, 95% CI: 1.175-2.493, p = 0.005) and postoperative pregnancy (RR: 0.649, 95% CI: 0.460-0.914, p = 0.013) were significantly correlated with endometrioma recurrence in the multivariate analysis. No significant associations were found between the recurrence rate and gravida, parity, body mass index, infertility, leiomyoma presence, the size of ovarian endometrioma, the presence of deep infiltrating endometriosis, disease stage or postoperative medication. CONCLUSIONS: The severity of dysmenorrhea and postoperative pregnancy were independent risk factors for the recurrence of ovarian endometriomas after surgery during the long-time follow up.
Assuntos
Endometriose/epidemiologia , Doenças Ovarianas/epidemiologia , Adulto , Dismenorreia/epidemiologia , Endometriose/cirurgia , Feminino , Seguimentos , Humanos , Doenças Ovarianas/cirurgia , Recidiva , Fatores de RiscoRESUMO
Methylene blue (MB) can ameliorate behavioral, neurochemical, and neuropathological impairments in animal models of acute and chronic neurodegenerative disorders, but the underlying mechanism remains unclear. Myocyte enhancer factor 2 (MEF2D) is known to promote neuronal survival in several models, and several survival and death signals converge on MEF2D and regulate its activity. Here, we investigated the role of MEF2D in the neuroprotective effect of MB against glutamate-induced toxicity in HT22 neuronal cells. Our results showed that MB, event at less than 100 nM, improved the viability of HT22 cells exposed to 2 mM glutamate. MB attenuated the mitochondrial impairment and quenches the reactive oxygen species (ROS) induced by glutamate. Surprisingly, MB at 50-200 nM did not affect the Nrf2/HO-1 pathway, an important endogenous anti-oxidative system. Further study showed that MB increased the transcription and translation of MEF2D. In addition, MB upregulated the expression of mitochondrial NADH dehydrogenase 6 (ND6) in a MEF2D-dependent manner. Knockdown of MEF2D abolished both MB-medicated increase of ND6 and MB-induced neuroprotection against glutamate-induced toxicity. Moreover, we showed that MB promoted Akt function activity, suppressed GSK-3ß activity, and increased MEF2D level in hippocampus of mice and HT22 cells. These findings for the first time demonstrate that MB protects HT22 neuronal cells against glutamate-induced cell death partially via the regulation of MEF2D-associated survival pathway.
Assuntos
Hipocampo/efeitos dos fármacos , Azul de Metileno/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologia , Hipocampo/metabolismo , Fatores de Transcrição MEF2/metabolismo , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Browning is the process of increasing the number of brite cells, which helps to increase energy expenditure and reduce obesity. Consumption of natural and non-toxic herbal extracts that possess the browning effect is an attractive anti-obesity strategy. In this study, we examined the browning effect of cinnamon extract. We found that cinnamon extract (CE) induced typical brown adipocyte multiocular phenotype in 3T3-L1 adipocytes. The treatment also increased brown adipocytes markers and reduced white adipocytes markers in the 3T3-L1 adipocytes. In ex vivo studies, we found that CE increased brown adipocytes markers in the subcutaneous adipocytes isolated from db/db mice and diet-induced obesity (DIO) mice. However, CE did not significantly affect UCP1 expression in the adipocytes isolated from perinephric adipose tissue and epididymal adipose tissue. ß3-adernergic receptor (ß3-AR) antagonist reduced the CE-enhanced UCP1 expression, suggesting an involvement of the ß3-AR activity. Oral administration of CE significantly increased UCP1 expression in the subcutaneous adipose tissue in vivo and reduced the body weight of the DIO mice. Taken together, our data suggest that CE has a browning effect in subcutaneous adipocytes. Our study suggests a natural non-toxic herbal remedy to reduce obesity.
Assuntos
Adipócitos Marrons/efeitos dos fármacos , Adipócitos Brancos/efeitos dos fármacos , Cinnamomum zeylanicum/química , Extratos Vegetais/farmacologia , Células 3T3-L1 , Adipócitos Marrons/metabolismo , Adipócitos Brancos/metabolismo , Animais , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/prevenção & controle , Gordura Subcutânea/citologia , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
Subcutaneous adipocytes in obese subjects have a lower sensitivity to catecholamine-induced lipolysis and a higher sensitivity to insulin anti-lipolytic effects compared to adipocytes in other adipose depots. Therefore, increasing lipolysis in subcutaneous adipocytes coupled with enhanced fatty acid oxidation may be an anti-obesity strategy. Schisandrin B (Sch B) is one of the most abundant active dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis which is a commonly prescribed Chinese medicinal herb. We found that Sch B reduced glycerolipid contents in 3T3-L1 adipocytes and subcutaneous adipocytes dissected from DIO mice. Sch B also activated hormone sensitive lipase (HSL) and increased lipolysis in these adipocyte in a protein kinase A-dependent manner. Interestingly, Sch B increased fatty acid oxidation gene expressions in these adipocytes, implying an increase in fatty acid oxidation after treatment. In in vivo model, we found that Sch B increased HSL phosphorylation, reduced glycerolipid levels and increased fatty acid oxidation gene expressions in the subcutaneous adipocytes in the DIO mice. More importantly, Sch B significantly reduced the subcutaneous adipocyte sizes, subcutaneous adipose tissue mass and body weight of the mice. Our study provides scientific evidence to suggest a potential therapeutic function of Sch B or Schisandra chinensis seed containing Sch B in reducing obesity.
Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Lignanas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Compostos Policíclicos/farmacologia , Gordura Subcutânea/metabolismo , Células 3T3-L1 , Animais , Peso Corporal , Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Glicólise/efeitos dos fármacos , Lignanas/química , Lipase/metabolismo , Metabolismo dos Lipídeos/genética , Lipólise/efeitos dos fármacos , Camundongos , Estrutura Molecular , Obesidade/genética , Obesidade/metabolismo , Oxirredução , Compostos Policíclicos/químicaRESUMO
Decitabine and CHG regimen (low-dose cytarabine and homoharringtonine with G-CSF) have been used for treating higher risk myelodysplastic syndrome (MDS). In this study, we retrospectively compared the efficacy and toxicity of the two regimens in 132 MDS patients. Complete remission (CR) was not significantly different between the groups (27.1% with decitabine vs. 30.6% with CHG, p = 0.657). The CR rate with decitabine (58.8%) was significantly higher than that with CHG (7.7%) (p = 0.007) among the patients with poor karyotypes. Five of 23 (21.7%) patients who failed to respond to decitabine achieved CR with CHG, while one of two patients achieved CR with decitabine after failure with CHG. Overall and relapse-free survival were not different between the groups. In conclusion, both decitabine and CHG regimen are effective for higher risk MDS; there is no cross resistance between the regimens. Decitabine might be a better choice for patients with poor karyotypes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/análogos & derivados , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Azacitidina/uso terapêutico , Citarabina/administração & dosagem , Decitabina , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Harringtoninas/administração & dosagem , Mepesuccinato de Omacetaxina , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Novel agents need to be developed to overcome the limitations of the current melanoma therapeutics. Atractylenolide I (AT-I) is a sesquiterpene compound isolated from atractylodis macrocephalae rhizoma. Previous findings demonstrated that AT-I exhibited cytotoxic action in melanoma cells. However, the molecular mechanisms of AT1's anti-melanoma properties remain to be elucidated. In the present study, the cell cycle-arrest and apoptosis-promoting effects as well as the ERK/GSK3ß signaling-related mechanism of action of AT-I were examined. B16 melanoma cells were treated with various concentrations of AT-1 (50, 75 and 100 µM) for 48 or 72 h. Cell cycle and apoptosis were analyzed by flow cytometry. Protein expression levels were detected by western blot analysis. AT-I treatment induced G1 phase arrest, which was accompanied by increased p21 and decreased CDK2 protein expression levels. Apoptosis was observed after AT-I treatment for 72 h, which was accompanied by activated caspase3 and 8. AT-I treatment significantly decreased phospho-ERK, phospho-GSK3ß, c-Jun and increased p53 protein expression levels. Lithium chloride (LiCl, 5 mM), a GSK3ß inhibitor, treatment alone did not increase the apoptosis of B16 cells, while pretreatment with LiCl markedly reversed AT-I-induced apoptosis. Additionally, AT-I-induced G1 phase arrest was partially reversed by LiCl pretreatment. In conclusion, ERK/GSK3ß signaling was involved in the apoptotic and G1 phase arrest effects of AT-I in melanoma cells.
Assuntos
Quinase 3 da Glicogênio Sintase/biossíntese , Lactonas/administração & dosagem , Melanoma Experimental/tratamento farmacológico , Proteína Quinase 3 Ativada por Mitógeno/biossíntese , Sesquiterpenos/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Humanos , Melanoma Experimental/genética , Melanoma Experimental/patologia , Camundongos , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteínas de Neoplasias/biossíntese , Transdução de Sinais/efeitos dos fármacosRESUMO
AIMS: Oxidative stress (OS) plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). This study was designed to uncover the cellular and biochemical mechanisms underlying the neuroprotective effects of tacrine-3-caffeic acid (T3CA), a novel promising multifunctional anti-Alzheimer's dimer, against OS-induced neuronal death. METHODS AND RESULTS: T3CA protected HT22 cells against high-concentration-glutamate-induced cell death in time- and concentration-dependent manners and potently attenuated glutamate-induced intracellular reactive oxygen species (ROS) production as well as mitochondrial membrane-potential (ΔΨ) disruption. Besides, T3CA significantly induced nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and increased its transcriptional activity, which were demonstrated by Western blotting, immunofluorescence, and antioxidant response element (ARE)-luciferase reporter gene assay. Further studies showed that T3CA potently up-regulated heme oxygenase-1 (HO-1), an endogenous antioxidative enzyme and a downstream effector of Nrf2, at both mRNA and protein levels. The neuroprotective effects of T3CA were partially reversed by brusatol, which reduced protein level of Nrf2, or by inhibiting HO-1 with siRNA or ZnPP-IX, a specific inhibitor of HO-1. CONCLUSIONS: Taken together, these results clearly demonstrate that T3CA protects neurons against OS-induced cell death partially through Nrf2/ARE/HO-1 signaling pathway, which further supports that T3CA might be a promising novel therapeutic agent for OS-associated diseases.
Assuntos
Ácidos Cafeicos/farmacologia , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Nootrópicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tacrina/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Transformada , Proteínas do Citoesqueleto/metabolismo , Ácido Glutâmico/farmacologia , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , Espécies Reativas de Oxigênio/metabolismo , TransfecçãoRESUMO
OBJECTIVE: To explore the feasibility of magnetic resonance cell imaging technology by using polyethylene imine (PEI)-coated magnetic nanoparticles of Fe4O4 (PEI-Fe4O4-MNPs) to track cell biology behavior. METHODS: Endocytic PEI-Fe4O4-MNPs in SHI-1 cells were observed by transmission electron microscopy (TEM) . Iron contents of nano-labeled cells were analyzed by inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and Prussian blue staining. The proliferation ability of labeled cells was detected by cell counting kit-8 (CCK-8) assay; the differentiation and colony-forming abilities were also observed. SHI-1 cells without endocytosing PEI-Fe4O4-MNPs were used as control. RESULTS: Our data showed that PEI-Fe4O4-MNPs could label SHI-1 cells. The labeling efficiency depended on the nanoparticles' concentration and the duration of cells treating. Inhibition rates of SHI-1cells labeled by 60-100 µg Fe/ml PEI-Fe4O4-MNPs were much higher than of 5-50 µg Fe/ml ones following treating by 5-100 µg Fe/ml PEI-Fe4O4-MNPs for 48 hrs. The expressions of CD11b and CD14 were (78.4±18.5)% and (18.7±2.9)% in control vs (83.3±14.2)% and (20.4±2.1)% in cells fractions treated by 30 µg Fe/ml PEI-Fe4O4-MNPs. Clony-forming rates of SHI-1 cells labeled by 0, 20 , 50 µg Fe/ml PEI-Fe4O4-MNPs were (25.20±7.22)%, (25.93±13.15)%, (23.37±9.33)%, respectively. Differentiation and colony-forming potentials of labeled cells were similar with control in the certain range of PEI-Fe4O4-MNPs concentration. CONCLUSION: SHI-1 cells were efficiently labeled by PEI-Fe4O4-MNPs with well biocompatibilities in proper range of concentration, the latter could be coupled with magnetic resonance imaging (MRI) to track cells in vivo.
Assuntos
Materiais Revestidos Biocompatíveis/química , Compostos Férricos/química , Nanopartículas/química , Polietilenoimina/química , Linhagem Celular Tumoral , Humanos , Imageamento por Ressonância Magnética , Magnetismo , Microscopia Eletrônica de TransmissãoRESUMO
The pathologic mechanisms of Alzheimer's disease (AD) have not been fully uncovered. Acrolein, a ubiquitous dietary pollutant and by-product of oxidative stress, can induce cytotoxicity in neurons, which might play an important role in the etiology of AD. Here, we examined the effects of Acrolein on the AD pathologies in vitro and in vivo. We found Acrolein induced HT22 cells death in concentration- and time-dependent manners. Interestingly, Acrolein increased proteins' levels of amyloid precursor protein (APP), ß-secretase (BACE-1) and the amyloid ß-peptide transporter receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels. In vivo, chronic oral exposure to Acrolein (2.5 mg/kg/day by intragastric gavage for 8 weeks) induced mild cognitive declination and pyknosis/atrophy of hippocampal neurons. The activity of superoxide dismutase was down-regulated while the level of malondialdehyde was up-regulated in rat brain. Moreover, Acrolein resulted in activation of astrocytes, up-regulation of BACE-1 in cortex and down-regulation of ADAM-10 in hippocampus and cortex. Taken together, our findings suggest that exposure to Acrolein induces AD-like pathology in vitro and in vivo. Scavenging Acrolein might be beneficial for the therapy of AD.
Assuntos
Acroleína/toxicidade , Doença de Alzheimer/induzido quimicamente , Encéfalo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas ADAM/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Desintegrinas/metabolismo , Imuno-Histoquímica , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos EspecíficosRESUMO
OBJECTIVE: To study the current situation of ten types of junk food consumption (assessed by World Health Organization) among children and adolescent as well as the contributing factors in Haidian District, Beijing so as to provide evidence for developing preventive and control measures and interventions. METHODS: A questionnaire survey was conducted to investigate the consumption of ten types of junk food practices in 1019 children and adolescent aged 8-16 years in Beijing Haidian District. RESULTS: One month prior to the study, 97.50% of the children and adolescent had eaten at least one type of junk food and 15.88% of them had eaten all types of them. Rates on having eaten deep fried food, pickled food, processed meat products, biscuits, coke or alike drinks, convenience/fast food, canned food, dried or preserved fruit, cold and sweet food, barbecue food etc. appeared to be 70.43%, 60.14%, 79.72%, 64.24%, 69.63%, 78.72%, 42.16%, 51.95%, 68.13%, 60.14% respectively. The rate on eaten more than once a day of these ten types were 26.95%, 36.88%, 34.84%, 32.97%, 27.40%, 28.18%, 37.91%, 26.15%, 37.39%, 22.10% respectively. The rates for "do not like" and "dislike" these ten types junk food were 10.96%, 27.42%, 7.08%, 12.11%, 6.56%, 6.59%, 17.80%, 13.59%, 3.42%, 5.19% respectively. Most of the children and adolescent ate junk food mainly during breakfast at home. Most of the surveyed children and adolescent did not have correct idea on nutrition of junk food. They received the information of junk food mainly from sources as advertisement on TV (67.95%), mother (9.02%), newspaper or magazines (6.71%). Many factors, such as individual factors (including physiological and psychological situations), social factors, family factors and the characteristics of food contributed to the eating junk food practices of children and adolescent. CONCLUSION: Eating junk food is a popular event among children and adolescent in Beijing Haidian District. Education strategies on nutrition should be developed and launched in order to help children develop their own healthy eating behaviors.