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A 44-year-old woman was transferred to the ICU of the First Affiliated Hospital of Jinan University for 2 days of persistent epigastric pain and 7 hours of unconsciousness. Her admission diagnosis was severe acute necrotizing pancreatitis (hypertriglyceridemia type) with multiple organ dysfunctions. The results of CT revealed a small area of necrotizing pancreatitis, which was not consistent with the severe clinical manifestations. Considering lack of hair and history of postpartum hemorrhage, hormone examination was carried out. According to the results of the examination, she was further diagnosed as Sheehan's syndrome and pituitary crisis. After hormone replacement therapy, her condition improved rapidly.
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Hipopituitarismo/diagnóstico por imagen , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Enfermedad Aguda , Adulto , Femenino , Terapia de Reemplazo de Hormonas/métodos , Humanos , Hipopituitarismo/complicaciones , Hipopituitarismo/tratamiento farmacológico , Pancreatitis Aguda Necrotizante/complicaciones , Tomografía Computarizada por Rayos X/métodosRESUMEN
MicroRNA (miR) is important regulators of gene expression, and aberrant miR expression has been linked to oncogenesis; however, little is understood about their contribution to colorectal cancer (CRC). Here, we determined that miR-23a is overexpressed in human colorectal cancer cell lines and tissues compared with that of normal cells. The stable over-expression of miR-23a in CRC cells was sufficient to promote cell proliferation in vitro and in vivo. Further studies showed that miR-23a can directly bind to the 3'untranslated region (3'UTR) of PDK4 mRNA and subsequently repress both the mRNA and protein expressions of PDK4. PDK4 negatively regulate CRC proliferation via suppressing PDH activity. Ectopic expression of PDK4 by transiently transfected with PDK4 vector encoding the entire coding sequence could reverse the effects of miR-23a on CRC proliferation. By this way, miR-23a promotes PDH activation and oxidative phosphorylation to generate sufficient ATP for cell proliferation. Our results illustrated that the up-regulation of miR-23a played an important role in CRC cell proliferation through direct repressing PDK4, suggesting a potential application of miR-23a in prognosis prediction and therapeutic application in CRC.
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Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/metabolismo , Fosforilación Oxidativa , Proteínas Serina-Treonina Quinasas/metabolismo , Piruvato Deshidrogenasa (Lipoamida)/metabolismo , Piruvato Deshidrogenasa Quinasa Acetil-TransferidoraRESUMEN
Objective: Labor induction during the late trimester of pregnancy is a common option of terminating pregnancy by inducing uterine contractions through medication or cervical mechanical dilation. However, there are few researches on the factors influencing the effectiveness of cervical ripening balloon combined with oxytocin in inducing labor. To explore factors affecting the efficacy of cervical ripening double balloon combined with oxytocin in labor induction. Methods: Using a convenient sampling method, this study retrospectively collected the clinical data of 230 pregnant women who underwent cervical ripening double balloon combined with oxytocin for labor induction in our hospital from September 2021 to August 2022. The included subjects were divided into a vaginal delivery group (n = 180) and a cesarean section group (n = 50) based on the delivery mode for comparing relevant indicators between the two groups. Results: The presence of acute chorioamnionitis (OR = 1.456, 95% CI: 1.257-2.112), fetal distress (OR = 1.371, 95% CI: 1.331-2.633), and the placement of cervical ripening balloon catheter for >12h (OR = 1.563, 95% CI: 1.231-3.263) were risk factors for successful application of cervical ripening double balloon combined with oxytocin for labor induction in pregnant women; while multi-gravidity (OR = 0.736, 95% CI: 0.455-0.875) was a protective factor. In addition, evaluation of the predictive value revealed that acute chorioamnionitis, fetal distress, the placement of cervical ripening balloon catheter for >12h, and gravidity all had certain predictive value for the failure of cervical ripening double balloon combined with oxytocin for labor induction, with the highest predictive value found through joint predictive (AUC: 0.931, 95% CI: 0.714-0.811). Conclusion: Cervical ripening double balloon combined with oxytocin for labor induction may have a high success rate in multigravida. Acute chorioamnionitis, fetal distress, and prolonged placement of the balloon may have a negative impact on the success rate of cervical ripening double balloon combined with oxytocin for labor induction.
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Although intestinal flora are crucial in maintaining immune homeostasis of the intestine, the role of intestinal flora in immune responses at other mucosal surfaces remains less clear. Here, we show that intestinal flora composition critically regulates the toll-like receptor 7 (TLR7) signaling pathway following respiratory influenza virus infection. TLR7 ligands rescued the immune impairment in antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for TLR7, MyD88, IRAK4, TRAF6, and NF-κB at steady state. Significant changes in the composition of culturable commensal bacteria reduced the expression levels of components of the TLR7 signaling pathway. Our results reveal the importance of intestinal flora in regulating immunity in the respiratory mucosa through the upregulation of the TLR7 signaling pathway for the proper activation of inflammasomes.
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Virus de la Influenza A/fisiología , Gripe Humana/microbiología , Gripe Humana/virología , Intestinos/microbiología , Microbiota , Mucosa Respiratoria/inmunología , Transducción de Señal , Receptor Toll-Like 7/inmunología , Animales , Femenino , Humanos , Virus de la Influenza A/inmunología , Gripe Humana/genética , Gripe Humana/inmunología , Intestinos/inmunología , Ratones , Ratones Endogámicos BALB C , Mucosa Respiratoria/virología , Receptor Toll-Like 7/genéticaRESUMEN
Patchouli alcohol (PA) is a kind of methanol extracted from traditional Chinese medicine Pogostemonis Herba. Our research aimed to observe the anti-influenza virus role of PA in vitro. 16HBE (human respiratory epithelial cell) was infected by H1N1 (A/FM1/1/47) to set the cell model. Then the 16HBE was co-cultivated with three kinds of immune cells: dendritic cells, macrophages, and monocytes, PA (the concentration is 10 µg/mL) was added as a treatment intervention for 24 h. The immune cells and the supernate were collected for RT-PCR and ELISA detection related to RLH (RIG-1-like helicases) pathway. Results showed that the IL-4 and IFN-γ in supernate were increased after H1N1 infection, and the PA treatment suppressed the expression of cytokines and the mRNA of RLH pathway. PA anti-influenza virus may through regulate the RLH singal pathway.
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Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Factores Inmunológicos/farmacología , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/inmunología , ARN Helicasas/inmunología , Sesquiterpenos/farmacología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/tratamiento farmacológico , Gripe Humana/enzimología , Gripe Humana/virología , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , ARN Helicasas/genética , Transducción de Señal/efectos de los fármacosRESUMEN
Ferroptosis is a newly found form of non-apoptotic regulated cell death that is essential for the advancement of cancer. Tiliroside (Til), an effective natural flavonoid glycoside of oriental paperbush flower, has been explored as a potential anticancer agent in a few cancer types. However, it is unclear whether and how Til could promote the death of triple-negative breast cancer (TNBC) cells by inducing ferroptosis. Our study determined that Til induced cell death and attenuated cell proliferation in TNBC cells in vitro and in vivo with less toxicity for the first time. Functional assays showed that ferroptosis was the predominant form that contributed to Til-induced cell death of TNBC. Mechanistically, Til induces ferroptosis of TNBC cells via independent PUFA-PLS pathways but is closely involved in the Nrf2/HO-1 pathway. Silencing of HO-1 substantially abrogated the tumor-inhibiting effects of Til. In conclusion, our findings suggest that the natural product Til exerted its antitumor activity on TNBC by promoting ferroptosis, and the HO-1/SLC7A11 pathway plays an indispensable role in Til-induced ferroptotic cell death.
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Antineoplásicos , Ferroptosis , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Flavonoides , Línea Celular TumoralRESUMEN
The antivirus effect of quercetin and oseltamivir on the Toll-like receptor 7 (TLR7) signaling pathway was observed when dendritic cells and macrophages were infected with H1N1. Leukomonocytes were obtained from umbilical cord blood and harvested after stimulation by recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (rhGM-CSF) and recombinant human Interleukin 4 (rhIL-4). Virus-infected cell model was established by human bronchial epithelial cells (16HBE) infected with H1N1. After immunological cells and virus-infected cells were co-cultured, quercetin and oseltamivir were also added into the medium as a treatment intervention. Then the immunological cells were collected for Real Time PCR (RT-PCR) and Western blot to determine the expression levels of genes related to TLR7 pathway. Viral infection led to cell death and increased the gene expression levels of TLR7 signal pathway. Quercetin and oseltamivir increased cell viability and reduced the expression levels of TLR7 signal pathway.
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Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Oseltamivir/farmacología , Quercetina/farmacología , Receptor Toll-Like 7/efectos de los fármacos , Western Blotting , Supervivencia Celular/efectos de los fármacos , Células Dendríticas/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Interleucina-3/farmacología , Interleucina-4/farmacología , Proteínas Recombinantes , Receptor Toll-Like 7/genéticaRESUMEN
Cancers are highly complex diseases that are characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming of the immune system play critical roles in tumor initiation and progression. Immunotherapy aims to reactivate antitumor immune cells and overcome the immune escape mechanisms of tumors. Represented by immune checkpoint blockade and adoptive cell transfer, tumor immunotherapy has seen tremendous success in the clinic, with the capability to induce long-term regression of some tumors that are refractory to all other treatments. Among them, immune checkpoint blocking therapy, represented by PD-1/PD-L1 inhibitors (nivolumab) and CTLA-4 inhibitors (ipilimumab), has shown encouraging therapeutic effects in the treatment of various malignant tumors, such as non-small cell lung cancer (NSCLC) and melanoma. In addition, with the advent of CAR-T, CAR-M and other novel immunotherapy methods, immunotherapy has entered a new era. At present, evidence indicates that the combination of multiple immunotherapy methods may be one way to improve the therapeutic effect. However, the overall clinical response rate of tumor immunotherapy still needs improvement, which warrants the development of novel therapeutic designs as well as the discovery of biomarkers that can guide the prescription of these agents. Learning from the past success and failure of both clinical and basic research is critical for the rational design of studies in the future. In this article, we describe the efforts to manipulate the immune system against cancer and discuss different targets and cell types that can be exploited to promote the antitumor immune response.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Receptores Quiméricos de Antígenos , Antígeno CTLA-4/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Humanos , Inhibidores de Puntos de Control Inmunológico , Factores Inmunológicos , Inmunoterapia/métodos , Ipilimumab/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/uso terapéutico , Receptor de Muerte Celular Programada 1RESUMEN
BACKGROUND: There have been some reports implicating the pharmacologic action of Dihydrosanguinarine (DHSA), but little research including the effects of it on cancer cells. PANC-1 cells have mutations in K-Ras and TP53, which respectively express mutant K-Ras and p53 protein, and the mutations in Ras/p53 have been believed with closely relationship to the occurrence of various tumors. PURPOSE: To reveal the inhibition of Dihydrosanguinarine on pancreatic cancer cells (PANC-1 and SW1990) proliferation by inducing G0/G1 and G2/M phase arrest via the downregulation of mut-p53 protein, inducing apoptosis and inhibiting invasiveness through the Ras/Mek/Erk signaling pathway. METHODS: Human pancreatic cancer cell lines were cultured with cisplatin and DHSA. Then, cell proliferation, the cell cycle and apoptosis were measured by CCK-8 and flow cytometry. The migratory and invasive abilities of pancreatic cancer cells were evaluated by transwell assay. The expression levels of mRNA and protein were measured by RT-PCR and western blotting. RESULTS: The results showed that DHSA treatment inhibited cell proliferation, migration and invasion in a time- and dose-dependent manner and led to induction of cell cycle arrest and apoptosis. G0/G1 and G2/M phase arrest inhibited the viability of PANC-1 cells by downregulating the expression of mut-p53 protein. Decreased levels of C-Raf and Erk phosphorylation in DHSA-treated PANC-1 and SW1990 cells were observed in a time- and dose-dependent manner. However, the total expression of p53 and Ras proteins had a different change in PANC-1 and SW1990 cells. CONCLUSIONS: Our findings offer the novel perspective that DHSA inhibits pancreatic cancer cells through a bidirectional regulation between mut-p53/-Ras and WT-p53/-Ras to restore the dynamic balance by Ras and p53 proteins.
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Antineoplásicos Fitogénicos/farmacología , Benzofenantridinas/farmacología , Isoquinolinas/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Proteína p53 Supresora de Tumor/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas p21(ras)/genética , Quinasas raf/genética , Quinasas raf/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
It is widely understood that commensal microbiota contributes to the maintenance of intestinal homeostasis through dynamic interactions with a body's immunity. And the immune regulation is important for the influenza vaccine's effectiveness after body injection, however, the mechanism between commensal microbiota and vaccine's effectiveness remains unknown. The impact that individual bacteria species have on the balance of the systemic immune system beyond the local intestinal mucosal tissues also remains less clear, and the related mechanism is still unknown. In this study, through the administration of various antibiotics, we examined the balance of helper T cell subsets in mice after inoculating them with the influenza virus and then, attempted to imitate the clinical practice in which patients are always prescribed with an antibiotic treatment in flu season. The data indicates that the mice in each group present differential immune responses in terms of the makeup of helper T cell subsets, although the Th17 cell activity seems to not be involved in the systemic immune modulation in the mice that are susceptible to the intervention of antibiotic. Th1, Th2, and anti-inflammatory regulatory T cells have been implicated in the contribution to the systemic immune response influenced by the antibiotic-induced dysbiosis. Thus we believe that the normal intestinal flora could maintain the immune balance and inhibit the inflammatory responses, which may be useful for clinical application to take intestinal flora into consideration when influenza vaccination was used.
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Disbiosis/etiología , Disbiosis/inmunología , Microbioma Gastrointestinal/inmunología , Infecciones por Orthomyxoviridae/inmunología , Orthomyxoviridae/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Animales , Modelos Animales de Enfermedad , Humanos , RatonesRESUMEN
Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.
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Over the past few decades, climate warming has caused profound changes in our living environment, and human diseases, including infectious diseases, have also been influenced by these changes. However, it remains unclear if a warm-wet climate can influence the infectivity of influenza and result in influenza pandemics. This study focused on observations of how the hydrothermal environment influences the infectivity of the influenza virus and the resulting immunoreactions of the infected mice. We used a manual climatic box to establish the following 3 environments with different temperatures and humidity: normal environment (T: 24 ± 1°C, RH: 50% ± 4%), wet environment (T: 24 ± 1 °C, RH: 95% ± 4%) and warm-wet environment (T: 33 ± 1 °C, RH: 95% ± 4%), and the mice were fed and maintained in these 3 different environments. After 14 days, half of the mice were infected with H1N1 (A/FM1/1/47, a lung adapted strain of the flu virus specific for the mouse lung) virus for 4 d After establishing the animal model, we observed the microstructure of the lung tissue, the Th1/Th2 T cell subsets, the Th17/Treg balance, the expression of cytokines in the peripheral blood serum and the expression of the immune recognition RLH signal pathway. The results showed that mice in different environments have different reaction. Results showed that after infection, the proportion of Th1/Th2 and Th17/Treg cells in the spleen was significantly increased, and these proportions were increased the most in the infected group kept in wet-hot conditions. After infection, the mRNA levels and protein expression of the RLH (RIG-1-like helicases) signal pathway components were up-regulated while the uninfected animals in the 3 diverse environments showed no significant change. The infected mice kept in the wet and warm-wet environments showed a slight elevation in the expression of RLH pathway components compared to infected mice maintained in the normal environment. Our study suggested that the warm-wet environment may have interfered with the immune response and balance. The mice kept in the warm-wet environment displayed immune tolerance when they were exposed to the influenza virus, and the body was not able to effectively clear the virus, leading to a persistent infection. A warm-wet climate may thus be a factor that contributes to influenza pandemics, people should focus on the warm-wet climate coming and advance prepare to vaccine manufacture.
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Exposición a Riesgos Ambientales , Interacciones Huésped-Patógeno , Subtipo H1N1 del Virus de la Influenza A/crecimiento & desarrollo , Infecciones por Orthomyxoviridae/patología , Animales , Citocinas/sangre , Humedad , Pulmón/patología , Ratones , Infecciones por Orthomyxoviridae/virología , Bazo/patología , Subgrupos de Linfocitos T/inmunología , TemperaturaRESUMEN
OBJECTIVE: To observe the anti-virus effects of andrographolide (AD) on the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) signaling pathway when immunological cells were infected with H1N1. METHODS: Leukomonocyte was obtained from umbilical cord blood by Ficoll density gradient centrifugation, and immunological cells were harvested after cytokines stimulation. Virus infected cell model was established by H1N1 co-cultured with normal human bronchial epithelial cell line (16HBE). The optimal concentration of AD was defined by methyl-thiazolyl-tetrazolium (MTT) assay. After the virus infected cell model was established, AD was added into the medium as a treatment intervention. After 24-h co-culture, cell supernatant was collected for interferon gamma (IFN-γ) and interleukin-4 (IL-4) enzyme-linked immunosorbent assay (ELISA) detection while immunological cells for real-time polymerase chain reaction (RT-PCR). RESULTS: The optimal concentration of AD for anti-virus effect was 250 µg/mL. IL-4 and IFN-γ in the supernatant and mRNA levels in RLRs pathway increased when cells was infected by virus, RIG-I, IFN-ß promoter stimulator-1 (IPS-1), interferon regulatory factor (IRF)-7, IRF-3 and nuclear transcription factor κB (NF-κB) mRNA levels increased significantly (P<0.05). When AD was added into co-culture medium, the levels of IL-4 and IFN-γ were lower than those in the non-interference groups and the mRNA expression levels decreased, RIG-I, IPS-1, IRF-7, IRF-3 and NF-κB decreased significantly in each group with significant statistic differences (P<0.05). CONCLUSIONS: The RLRs mediated viral recognition provided a potential molecular target for acute viral infections and andrographolide could ameliorate H1N1 virus-induced cell mortality. And the antiviral effects might be related to its inhibition of viral-induced activation of the RLRs signaling pathway.
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Antivirales/farmacología , ARN Helicasas DEAD-box/metabolismo , Diterpenos/farmacología , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , Leucocitos Mononucleares/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Proteína 58 DEAD Box , ARN Helicasas DEAD-box/genética , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Células Dendríticas/virología , Sangre Fetal/citología , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Gripe Humana/virología , Interferón beta/genética , Interferón beta/metabolismo , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Macrófagos/efectos de los fármacos , Macrófagos/virología , FN-kappa B/genética , FN-kappa B/metabolismo , Regiones Promotoras Genéticas/efectos de los fármacos , Regiones Promotoras Genéticas/inmunología , ARN Mensajero/metabolismo , Receptores Inmunológicos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Transducción de Señal/inmunologíaRESUMEN
OBJECTIVE: To investigate the effect of LBP on differentiation and maturation of healthy human peripheral blood-derived dendritic cells cultured in different tumor microenvironment in vitro, and discuss the molecular and immunological mechanisms of LBP in treatment of tumor. METHODS: In this study, we procured the peripheral blood-derived dendritic cells precursor cell by the Density gradient centrifugation method, and used the tumor-cell supernatant to prepare conditioned medium. The GM-CSF and IL-4 induced DCs precursor cell differentiation to DCs, the TNF-α promoted the immature DCs developed to mature DCs. In this way, we detected the influence of LBP on the expressions of surface molecules of DCs cultured in different environments, and especially on the role of related-immunity and NF-κB activity. RESULTS: In LBP-treated group, the molecular phenotype of DCs, its capacity to stimulate allogeneic lymphocyte proliferation, and the levels of IL-12p70 and IFN-γ secretion were higher than the untreated group (p < 0.05), with statistical significance. Meanwhile the expression of NF-κB of the DCs in the medium treated by the LBP was higher than the untreated group (p < 0.05), also with statistical significance. Between the two different tumor microenvironment groups, the cell nucleus protein NF-κB expression is obviously different, the hepG2.2.15 group higher than the hepG2 group. CONCLUSION: LBP could increase the expression of the phenotype of DCs, the secretion of IL-12p70 and IFN-γ in MLR, and enhance the NF-κB expression, especially in the virus-related group, suggesting LBP plays the anti-tumor role stronger in the virus-related environment and this phenomenon correlates with the NF-κB signaling pathway.
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Carcinoma Hepatocelular/inmunología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Medicamentos Herbarios Chinos/farmacología , Neoplasias Hepáticas/inmunología , Transducción de Señal/efectos de los fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Células Dendríticas/metabolismo , Células Hep G2 , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-12/metabolismo , Interleucina-4/genética , Interleucina-4/inmunología , Interleucina-4/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos/metabolismo , FN-kappa B/genética , FN-kappa B/inmunología , FN-kappa B/metabolismo , Transducción de Señal/genética , Transducción de Señal/inmunología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To investigate the anticancer effects of desacetyluvaricin (DES) on hepatocellular carcinoma (HCC) in vitro, and to study its mechanism. MATERIALS AND METHODS: Using DES and cisplatin (DDP) to intervene the cell lines of hepatocarcinoma G2.2.15 (HepG2.2.15) and HepG2, by detecting the expression of HBxAg by immunofluorescence method, the cell cycle and apoptosis by flow cytometry method (FCM), and expression of NF-κB protein by ELISA. RESULTS: DES and DDP showed to suppress proliferation of HepG2.2.15 and HepG2; they increase the S-phase cells and decrease G2/M phase cells. DES and DDP both could promote the apoptosis and reduce the expression of NF-κB on the cell line. DES and DDP both can suppress the expression of HbxAg in HepG2.2.15. There were no statistical differences of the above results between these two drugs (P > 0.05). CONCLUSIONS: DES possesses anticancer effect on hepatocarcinoma. The possible mechanism might be due to promotion the apoptosis of the cancer cells, and downregulate the expression of HBx andNF-κB protein. DES is a kind of natural products, Because of the lighter clinical side effects; our observations suggest that DES has the potential to be explored as an effective anticancer agent for HCC.
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OBJECTIVE: To study the immunologic function of dendritic cells (DCs) cultured in two kinds of hepatoma cell line's supernatant and the enhancing effects of carboxymethylpachymaran (CMP) on DCs. METHODS: DCs were harvested after stimulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 from umbilical cord blood using density-gradient centrifugation method. Cultured supernatant of two hepatoma cell lines (HepG2 and HepG2.2.15) were collected for condition medium (CM) according to a volume ratio of supernatant to incomplete RPMI-1640 medium, which was 3:1. CMP was dissolved in incomplete RPMI-1640 medium. Experimental groups were divided according to the culture medium, either CM or with CMP in it. DCs subsets CD83, CD86, CD1a, and d-related human leukocyte antigens (HLA-DR) were analyzed by flow cytometry. The proliferation ability of allogeneic T cells in mixed lymphocyte reaction (MLR) stimulated by DCs was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. IL-12p70, interferon-γ (IFN-γ), and nuclear factor κB (NF-κB) were detected by enzyme-linked immunosorbent assay analysis. RESULTS: The proliferation of lymphocytes and secreting level of IL-12 and expression of phenotype of DCs cultured in two kinds of CM were lower than those of normal group (P <0.01). Compared with the normal group, groups treated with CMP showed a higher expression level of DCs subsets, lymphocyte reproductive activity, as well as IL-12 and IFN-γ secretion levels. Groups treated with CMP also demonstrated higher levels of DCs phenotype expression and IL-12 and IFN-γ secretion in supernatant of MLR and higher lymphocyte reproductive activity compared with CM group (P <0.05). Compared with the normal group, the expression level of NF-κB in DCs nuclear was higher in CMP groups but lower in two CM groups (P <0.05). After CMP was added, the NF-κB expression levels of two CM groups were increased compared with levels before CMP was added (P <0.05). However, there was no significant difference between the two CM groups (P >0.05). CONCLUSIONS: Two kinds of hepatoma cell line's supernatant can inhibit the immunologic function of DCs. This suppressive effect may be related to the inhibition of NF-κB/Rel pathway. CMP may up-regulate the DCs function by activating the NF-κB/Rel pathway.
Asunto(s)
Carcinoma Hepatocelular/patología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Glucanos/farmacología , Neoplasias Hepáticas/patología , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo , Carcinoma Hepatocelular/ultraestructura , Línea Celular Tumoral , Forma de la Célula , Humanos , Inmunofenotipificación , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Neoplasias Hepáticas/ultraestructura , Prueba de Cultivo Mixto de Linfocitos , Fracciones Subcelulares/efectos de los fármacosRESUMEN
BACKGROUND: In order to observe the protective therapeutic action and mechanism of Liuwei Dihuang Decoction, Buzhong Yiqi Decoction, and Compound Danshen Decoction on Myelosuppression induced by cyclophosphamide. MATERIALS AND METHODS: The mice model was established by intraperitoneal injected with 100 mg/kg cyclophosphamide by human and mice dose conversion on the 9(th), 11(th), 13(th) days during the experiment. Flow cytometry (FCM) was used for detecting the number of cells and investigating bone marrow cell cycles. Spleen was taken out and the mRNA expression level of thrombopoietin (TPO) and c-Mpl were detected by Q-PCR, and c-Mpl in spleen in order to discuss the mechanism of myelosuppression and the protective effects of traditional Chinese medicine. RESULTS: Both Liuwei Dihuang Decoction Group and Buzhong Yiqi Decoction Group can accelerate bone marrow hematopoietic stem progenitor cells (HSPCs) in marrow-suppressed mice and enhance cell proliferation by promoting cell cycles from G0/G1 phase to access into S, G2/M phase. And at the same time these Chinese decoctions can increase the mRNA expression level of TPO and c-Mpl in spleen. CONCLUSION: Researched showed that Chinese formula take effect by affecting these genes on myelosuppressed mice.
RESUMEN
BACKGROUND: Previous studies suggest that annonaceous may cause permeability glycoprotein (P-gp) function to abate, leading to cell apoptosis. It has also been reported that annonaceous acetogenins affect hepatocellular carcinoma (HCC) cells in the G1 phase, leading to apoptosis. Desacetyluvaricin (Des), a new type of annonaceous acetogenin monomer, has a significant effect on HCC, with few side effects. OBJECTIVES: To investigate the effect of Des on the expression of Toll-like receptor 4 (TLR4) and P53 protein in HCC. MATERIALS AND METHODS: HCC HepG2.2.15 cell was cultured by routine method. HepG2.2.15 cells were divided into three groups: control group, treated with Des and DDP (cisplatin) which were examined by immunofluorescence flow cytometry for expression of TLR4 and P53. RESULTS: TLR4 was expressed by more cells in the Des group than in the cisplatin or serum-only groups (71.94%, 42.64%, and 37.16%, respectively; Des vs.cisplatin: p < 0.05; Des vs. serum only: p < 0.05), with no difference between the cisplatin and serum-only groups (p > 0.05). P53 was expressed by more cells in the Des and cisplatin groups than in the serum-only group (32.6%, 31.5% and 3.3%, respectively; Des vs. serum only, p < 0.05; cisplatin vs. serum only, p < 0.05), with no difference between the Des and cisplatin groups (p > 0.05). CONCLUSIONS: Des increases TLR4 and P53 expression in HCC cells. Improved immune recognition by the former effect and induction of apoptosis by the latter could be the mechanisms of Des's clinical effects on HCC.