RESUMO
Natural plant-derived baicalein which is extracted from Chinese herb Scutellaria baicalensis Georgi belongs to the flavonoid compounds and possesses multiple pharmacological activities. In this study, we designed and synthesized new series of derivatives of baicalein (BE) through catalytic coupling reactions, and screened for their antiviral activity against arboviruses including Chikungunya virus (CHIKV), West Nile virus (WNV) or Zika virus (ZIKV). Our results revealed for the first time that BE and its derivatives had potent anti-CHIKV, anti-WNV and anti-ZIKV effects. And modification of 8 or 4' position could lead to obtain potent antiviral compounds against CHIKV, WNV and ZIKV with lower cytotoxicity. Among the baicalein derivatives, C3 and F3 showed the most potent antiviral activities against CHIKV, WNV and ZIKV, which were 5-10 times more potent than baicalein. Our findings will provide research basis for the development of baicalein derivatives as effective antiviral agents.
Assuntos
Arbovírus , Vírus Chikungunya , Vírus do Nilo Ocidental , Infecção por Zika virus , Zika virus , Antivirais/farmacologia , Antivirais/uso terapêutico , Flavanonas , Humanos , Infecção por Zika virus/tratamento farmacológicoRESUMO
Non-alcoholic fatty liver disease (NAFLD) associated with obesity may progress to non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma (HCC). Retinoic acid induced 16 (RAI16) plays an important role in cell apoptosis and is also a potential marker for HCC. Here we aimed to test the effect of RAI16 deficiency on liver pathology in high-fat diet (HFD) fed mice. Wild type (WT) and RAI16 knockout (RAI16-/-) C57BL/6 mice were fed with HFD or chow for up to 12 months. With consumption of HFD diet, RAI16-/- mice on HFD developed much more excess fatty liver within 4 months than WT mice on HFD. The expressions of fatty acid synthesis associated molecules Ppar-γ, Srebp-1c and Fas were further increased in RAI16-/- mice compared with WT mice on HFD. Macrophage infiltration related molecules Mcp-1 and F4/80 and pro-inflammatory factor Lcn2 were significantly increased in RAI16-/- mice compared with WT mice on HFD. Conclusively, RAI16 deficiency exacerbated HFD-induced liver injury, associated with increased inflammation. These findings indicate that RAI16 plays an important role in HFD-induced liver pathology and might be considered as a target for treatment of NAFLD. SIGNIFICANCE: 1. RAI16-/- mice on HFD developed much more excess fatty liver. 2. RAI16-/- mice showed more macrophage infiltration and proinflammation.
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Dieta Hiperlipídica/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/genética , Animais , Apoptose , Quimiocina CCL2/metabolismo , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica , Inflamação , Metabolismo dos Lipídeos , Lipocalina-2/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , ProteínasRESUMO
Ulcerative colitis (UC) is a chronic intestinal inflammatory disease. The receptor-interacting protein kinase 3 (RIP3) was reported to be involved in many inflammatory disease. However, the mechanism of RIP3 in the pathogenesis of UC is still unclear. To investigate the effects and possible mechanism of RIP3 in UC pathogenesis, RIP3-/- mice was used in dextran sulfate sodium (DSS)-induced colitis model. It was found that by DSS-induced colitis, RIP3-/- mice showed significantly enhanced colitis symptoms, including increased weight loss, colon shortening, and colonic mucosa damage and severity, but decreased production of interleukin 6 and interleukin 1ß. The results showed that RIP3 deficiency could not ameliorate but exacerbate the severity of colitis. On the mechanism, it was found that messenger RNA expressions of several repair-associated cytokines including interleukin 6, interleukin 22, cyclooxygenase 2, epithelial growth factor receptor ligand Epiregulin and matrix metalloproteinase 10 were siginificant decreased in RIP3-/- mice. Thus, RIP3-/- mice exhibited an impaired tissue repair in response to DSS. In a conclusion, RIP3 deficiency exerted detrimental effects in DSS induced colitis partially because of the impaired repair-associated cytokines expression.
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Colite Ulcerativa/complicações , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Inflamação/etiologia , Proteína Serina-Treonina Quinases de Interação com Receptores/fisiologia , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Citocinas/genética , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Índice de Gravidade de DoençaRESUMO
Although much progress has been made in antiviral agents against hepatitis C virus (HCV) in recent years, novel HCV inhibitors with improved efficacy, optimized treatment duration and more affordable prices are still urgently needed. Here, we report the identification of a natural plant-derived lignan, trachelogenin (TGN), as a potent entry inhibitor of HCV without genotype specificity, and with low cytotoxicity. TGN was extracted and purified from Caulis trachelospermi, a traditional Chinese herb with anti-inflammatory and analgesic effects. A crucial function of TGN was the inhibition of HCV entry during a post-binding step without affecting virus replication, translation, assembly and release. TGN blocked virus infection by interfering with the normal interactions between HCV glycoprotein E2 and the host entry factor CD81, which are key processes for valid virus entry. In addition, TGN diminished HCV cell-to-cell spread and exhibited additional synergistic effects when combined with IFN or telaprevir. In conclusion, this study highlights the effect of a novel HCV entry inhibitor, TGN, which has a target that differs from those of the current antiviral agents. Therefore, TGN is a potential candidate for future cocktail therapies to treat HCV-infected patients.
Assuntos
4-Butirolactona/análogos & derivados , Hepacivirus/fisiologia , Tetraspanina 28/metabolismo , Internalização do Vírus/efeitos dos fármacos , 4-Butirolactona/farmacologia , Relação Dose-Resposta a Droga , Genótipo , Hepacivirus/genética , Hepatócitos/virologia , Humanos , Estrutura Molecular , Tetraspanina 28/genética , Montagem de Vírus/efeitos dos fármacos , Liberação de Vírus , Replicação Viral/efeitos dos fármacos , Replicação Viral/fisiologiaRESUMO
West Nile virus (WNV) is an important neurotropic virus that accounts for the emergence of human arboviral encephalitis and meningitis. The interaction of WNV with signaling pathways plays a key role in controlling WNV infection. We have investigated the roles of the AKT and ERK pathways in supporting WNV propagation and modulating the inflammatory response following WNV infection. WNV established a productive infection in neuronal cell lines originated from human and mouse. Expression of IL-11 and TNF-α was markedly up-regulated in the infected human neuronal cells, indicating elicitation of inflammation response upon WNV infection. WNV incubation rapidly activated signaling cascades of AKT (AKT-S6-4E-BP1) and ERK (MEK-ERK-p90RSK) pathways. Treatment with AKT inhibitor MK-2206 or MEK inhibitor U0126 abrogated WNV-induced AKT or ERK activation. Strong activation of AKT and ERK signaling pathways could be detectable at 24 h after WNV infection, while such activation was abolished at 48 h post infection. U0126 treatment or knockdown of ERK expression significantly increased WNV RNA levels and viral titers and efficiently decreased IL-11 production induced by WNV, suggesting the involvement of ERK pathway in WNV propagation and IL-11 induction. MK-2206 treatment enhanced WNV RNA replication accompanied with a moderate decrease in IL-11 production. These results demonstrate that engagement of AKT and ERK signaling pathways facilitates viral infection and may be implicated in WNV pathogenesis.
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Tick-borne encephalitis virus (TBEV) belonging to arboviruses is a major member of zoonotic pathogens. TBEV infection causes severe human encephalitis without specific antiviral drugs. Due to its use of antiviral drug against a wide range of viruses, we investigated antiviral effect of ribavirin against TBEV in susceptible human cell lines A549 and SH-SY5Y. Ribavirin displayed minor cytotoxicity on multiple cell lines. Ribavirin obviously impaired TBEV replication and protected the infected cells from cytopathic effect. Importantly, ribavirin markedly inhibited TBEV propagation, as evidenced by impairment of TBEV production and viral RNA replication. Treatment with ribavirin (co-treatment and post-treatment) led to a dose-dependent reduction in TBEV titers as well as the viral RNA levels. Antiviral protein myxovirus resistance A mRNA expression was significantly up-regulated and signal transducer and activator of transcription 3 was activated in TBEV-infected A549 cells upon the ribavirin treatment. Induction of inflammatory cytokine tumor necrosis factor alpha by TBEV was decreased in A549 cells with the treatment of ribavirin, whereas interleukin 1 beta release appeared to be unaffected. These results suggest that ribavirin might represent a promising safe and effective antiviral drug against TBEV.
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A novel echocardiographic method, vector flow mapping (VFM), acquires velocity vector from color Doppler velocity data. The purpose of this study was to evaluate whether VFM could provide useful information on intracardiac flow and helpful to evaluate left ventricular (LV) function. Thirty-eight patients with uremia undergoing hemodialysis and 30 healthy volunteers were enrolled. The maximum vector velocity, maximum diameter and duration of the intracardiac vortex were measured using VFM software during systole and diastole. The maximum vector velocity of the vortex and the peak velocities at the basal septum and lateral mitral annulus measured by tissue Doppler imaging (TDI) were correlated. The maximum diameter and duration of vortex formation were significantly higher in uremic patients compared with the control group during the ejection phase (40.6 ± 7.9 cm/sec vs. 28.1 ± 3.9 cm/sec; 297.1 ± 22.1 msec vs. 145.4 ± 19.3 msec, all P < 0.001). The maximal diameters of the vortex were higher in uremic patients compared with the control group during diastole (25.6 ± 3.4 mm vs. 16.4 ± 2.1 mm; 34.3 ± 3.1 mm vs. 26.8 ± 3.9 mm; 37.5 ± 2.4 mm vs. 20.9 ± 2.1 mm; all P < 0.001). The maximum vector velocities were lower in mid-diastole and late diastole (23.6 ± 2.3 cm/sec vs. 45.2 ± 3.7 cm/sec; 31.9 ± 2.9 cm/sec vs. 54.7 ± 3.2 cm/sec, all P < 0.001). There was a correlation between the maximum vector velocity of the vortex in mid-diastole and E'/A' at the septum and lateral mitral annulus (r = 0.70, r = 0.76, P < 0.001). Vortex can be utilized to provide intracardiac dynamic information using VFM and it may be a good supplement for evaluating LV function.
Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Volume Sistólico , Uremia/diagnóstico por imagem , Uremia/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Velocidade do Fluxo Sanguíneo , Ecocardiografia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Uremia/complicações , Disfunção Ventricular Esquerda/etiologiaRESUMO
OBJECTIVE: To investigate the expression of miR-23a and metastasis suppressor 1 (MTSS1) and their clinical significance in colon carcinoma. METHODS: A total of 92 cases of colon carcinomas were collected with both the tumor and paired normal tissue samples for the study. The miR-23a targeting MTSS1 was evaluated by luciferase reporter vector. Cell invasion potential was evaluated by trans-well invasion assay. In-situ hybridization and immunohistochemistry were used to detect miR-23a and MTSS1 expression. RESULTS: MiR-23a downregulated the expression of MTSS protein and enhanced the invasiveness of colon carcinoma. The expression rates of miR-23a and MTSS1 were 87.0% (80/92) and 17.4% (16/92) in colon carcinoma cases, respectively (P < 0.01). The up-regulation of miR-23a expression was associated with an advanced clinical stage (P = 0.029) and depth of invasion (P = 0.000). The expression of miR-23a was higher in the tumors with lymph node metastasis than those without (P = 0.041). Down-regulation of MTSS1 expression was associated with an advanced clinical stage (P = 0.027) and depth of invasion (P = 0.017). The expression of MTSS1 was lower in the tumors with lymph node metastasis than those without (P = 0.009). The expression of miR-23a had significantly negative correlation with that of MTSS1 (r = -0.594, P = 0.013). CONCLUSIONS: MiR-23a expression promotes colon carcinoma cell growth, invasion and metastasis through inhibition of MTSS gene. Both the low expression of MTSS1 and high expression of miR-23a may serve as important biological markers for the malignant phenotypes of colon cancer, such as invasion and metastasis.
Assuntos
Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Hibridização In Situ , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Complex decongestive therapy (CDT) is currently recommended as the standard treatment for lymphedema. CDT is a four-step detumescence therapy that can effectively treat upper limb lymphedema after breast cancer surgery, and is considered non-invasive, painless and without side effects. AIM: To determine the effectiveness of a six-step CDT involving a foam granule bandage for the treatment of upper extremity lymphedema pressure after breast cancer surgical intervention. METHODS: The study included 100 patients with upper extremity lymphedema after breast cancer surgery. The surgical methods were mastectomy plus axillary lymph node dissection and breast preservation plus sentinel lymph node biopsy. The study population was further divided into the experimental group and control group with 50 cases in each group. The control group was given conventional CDT (four-step method), which included skin care, freehand lymphatic drainage, foam granule pressurized bandage, and functional exercise. In the experimental group, a six-step CDT method was applied that involved a foam particle bandage combined with air wave pressure therapy in addition to the four steps of conventional CDT. Patients in both groups were given one course of treatment daily (20 times), and the changes in body moisture and subjective symptoms were measured before and after treatment, preoperatively and 20 times after treatment. RESULTS: No statistically significant differences in 50-Hz bioelectrical impedance and extracellular moisture ratio were observed between the two groups before treatment, suggesting comparability of the baseline data. After treatment, the 50-Hz bioelectrical impedance of the experimental group was significantly higher than that in the control group, and the extracellular moisture ratio was significantly lower than that in the control group. A comparison of the differences between the two groups before and after treatment indicated that the treatment effect in the experimental group was better than that in the control group. After 20 treatments, according to subjective evaluations, the tightness and swelling of the limbs in the experimental group were significantly reduced as compared with those in the control group. CONCLUSION: The six-step CDT method can effectively reduce lymphedema, promote lymphatic circulation, and alleviate the subjective symptoms of patients, and thereby improve the quality of life and treatment compliance among patients.
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OBJECTIVE: to investigate the expression of the hsa-miR-155 in serum of endometrial cancer and its clinical significance. METHODS: collected 44 cases blood specimens before surgery operation from Sep. 2008 to Dec. 2009, and collected 12 cases blood specimens from the health of volunteers in comparison. Real time quantity PCR was used to detect the expression of hsa-miR-155 in those specimens and analyzed clinical pathological with the expression of hsa-mir-155 in endometrial cancer. RESULTS: the expression of hsa-miR-155 was (3.9 ± 0.7) in endometrial cancer, which was significantly higher than that in control group (P < 0.01). The expressions of hsa-miR-155 were (3.7 ± 0.6), (3.9 ± 0.6) and (3.7 ± 0.6) times in well, moderately and poorly differentiated endometrial cancer, respectively, while there were not significant difference (P > 0.05). The expressions were (3.8 ± 0.6) and (3.9 ± 0.6) times between endometrioid adenocarcinoma and non-endometrioid adenocarcinoma, and there were significant difference (P > 0.05). The expressions were (2.1 ± 0.4) and (5.6 ± 0.8) times in stage I - II and III - IV endometrial cancer, respectively, in which there were significant difference (P < 0.05). The expressions of hsa-miR-155 were (5.5 ± 0.5) and (1.9 ± 0.2) times between lymph node metastasis and without lymph node metastasis in endometrial cancer, in which there were significant difference (P < 0.01). CONCLUSION: Hsa-miR-155 may play an important role in the proliferation, and metastasis of endometrial cancer, which may be a indicator in the diagnosis and prognosis of endometrial cancer and may be used as a predictive biomarker.
Assuntos
Carcinoma Endometrioide/sangue , Neoplasias do Endométrio/sangue , MicroRNAs/sangue , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma Endometrioide/patologia , Estudos de Casos e Controles , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase/métodos , PrognósticoRESUMO
The lymphocyte-to-monocyte ratio (LMR), as a surrogate marker of systemic inflammation, has been found to be a novel prognostic indicator in various malignancies. Data from 672 advanced epithelial ovarian cancer (EOC) patients treated with neoadjuvant chemotherapy (NAC) followed by debulking surgery were analyzed, and the prognostic value of LMR were evaluated. The optimal cutoff point of LMR in prediction of survival was defined as 3.45 through receiver operating characteristics curve analysis. Patients with low LMR (≤3.45) at diagnosis tended to have more adverse clinical features, such as higher histological grade, chemotherapy resistance, and residual tumor >1cm after debulking surgery. No significant correlation was found between LMR level and age and histological type. Moreover, after NAC, the complete remission (CR) rate for the low-LMR group was lower than those for the high-LMR group (P<0.05). Patients with low LMR had poorer progression-free survival (PFS; P<0.001) and overall survival (OS; P<0.001). Multivariate analysis revealed that low LMR was an independent adverse predictor for PFS and OS. Results indicated that low LMR at diagnosis is a novel independent prognostic factor for advanced EOC. However, prospective study is needed to validate this prognostic factor and biological studies should further investigate the mechanisms underlying the correlation between low LMR and poor prognosis in advanced EOC.
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Influenza H7N9 virus infection causes an acute, highly contagious respiratory illness that triggers cell death of infected cells and airway epithelial destruction. RIP3 is a key regulator of cell death responses to a growing number of viral and microbial agents. This study aimed to investigate the role of RIP3 in inflammation of influenza H7N9 virus infection. Here, RIP3 knock out (RIP3-/-) mice and littermate wild type mice were infected intranasally with influenza H7N9 virus (A/Fujian/S03/2015) to determine the contribution of RIP3 to the inflammatory response of influenza H7N9 virus infection. It was found that RIP3-/- mice infected with H7N9 virus showed higher survival and less weight loss, compared with wild type littermate mice. In addition, RIP3-/- mice had fewer regions of edema, infiltration with inflammatory cells, and alvelolar collapses, and the secretions of IL-1ß, IL-6, RANTES and MIP-1 in BALF were significantly decreased on days 3 and 7 p.i. when compared with WT mice. Moreover, caspase 1/IL1ß signaling was found to be invovled in RIP3 associated imflammation of influenza H7N9 virus, but not RIP3/MLKL dependent necrosis. In the conclusion, our results indicated that RIP3 deficiency can protect mice from the infection of influenza H7N9 virus by downregulating caspase 1/IL1ß signaling, which provided edivence of the RIP3 invovled necroptosis independent manner.
Assuntos
Caspase 1/metabolismo , Citocinas/metabolismo , Subtipo H7N9 do Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Proteína Serina-Treonina Quinases de Interação com Receptores/imunologia , Animais , Apoptose/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Caspase 1/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Influenza Humana/mortalidade , Influenza Humana/patologia , Influenza Humana/virologia , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Knockout , Necrose/imunologia , Proteínas Quinases/imunologia , Proteínas Quinases/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Transdução de Sinais , Redução de PesoRESUMO
Despite recent progress in the development of hepatitis C virus (HCV) inhibitors, cost-effective antiviral drugs, especially among the patients receiving liver transplantations, are still awaited. Schisandra is a traditional medicinal herb used to treat a range of liver disorders including hepatitis for thousands of years in China. To isolate the bioactive compounds of schisandra for the treatment of HCV infection, we screened a schisandra-extracts library and identified a tetracyclic triterpenoid, schizandronic acid (SZA), as a novel HCV entry inhibitor. Our findings suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion-cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infection in vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations.
Assuntos
Antivirais/administração & dosagem , Hepacivirus/efeitos dos fármacos , Hepatite C/virologia , Schisandra/química , Triterpenos/administração & dosagem , Animais , Antivirais/química , Antivirais/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Genótipo , Células HEK293 , Hepacivirus/genética , Hepatócitos , Humanos , Interferons/administração & dosagem , Interferons/farmacologia , Camundongos , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Ligação Viral , Internalização do Vírus/efeitos dos fármacos , Replicação ViralRESUMO
Our previous study reported that retinoic acid induced 16 (RAI16) could enhance tumorigenesis in hepatocellular carcinoma (HCC). However, the cellular functions of RAI16 are still unclear. In this study, by immunoprecipitation and tandem (MS/MS) mass spectrometry analysis, we identified that RAI16 interacted with the type II regulatory subunit of PKA (PKA-RIIα), acting as a novel protein kinase A anchoring protein (AKAP). In addition, RAI16 also interacted with heat shock protein 70 (HSP70) and 14-3-3θ. Further studies indicated that RAI16 mediated PKA phosphorylation of HSP70 at serine 486, resulting in anti-apoptosis events. RAI16 was also phosphorylated by the anchored PKA at serine 325, which promoted the recruitment of 14-3-3θ, which, in turn, inhibited RAI16 mediated PKA phosphorylation of HSP70. These findings offer mechanism insight into RAI16 mediated anti-apoptosis signaling in HCC.
Assuntos
Proteínas 14-3-3/metabolismo , Proteínas de Ancoragem à Quinase A/metabolismo , Subunidade RIIalfa da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas/metabolismo , Apoptose/fisiologia , Carcinoma Hepatocelular/patologia , Linhagem Celular , Sobrevivência Celular , Transformação Celular Neoplásica , Células HEK293 , Humanos , Neoplasias Hepáticas/patologia , Fosforilação , Transdução de Sinais , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: To investigate application of fetal echocardiography in diagnosis of fetal arrhythmia and its clinical significance. METHODS: Fetal echocardiography was performed on 725 fetuses for evaluation of fetal heart structures and arrhythmias. Two-dimensional, M-mode, Color M-mode and pulsed Doppler echocardiography were used. RESULTS: Ninety fetuses were documented with fetal arrhythmia, the commonest fetal arrhythmia encountered in 72 cases extrasystole was (65 atrial extrasystoles, 7 ventricular extrasystoles), followed by bradycardia in 9 cases, tachycardia in 6 cases, 2:1 atrioventricular block in 2 cases, atrial flutter in 1 case. There were 4 fetuses with arrhythmias and structural heart diseases: 2 fetuses were found died in uterus within two-week follow-up (1 with single ventricle and pulmonary stenosis, 1 with cardiac rhabdomyoma, fetal echocardiographic findings were confirmed at autopsy), another 2 cases (1 with mitral atresia and 1 with atrioventricular canal defect, autopsy confirmed the fetal echocardiographic diagnoses) received termination of pregnancy later. One 38-week fetus with atrial flutter underwent cesarean section, neonatal ECG confirmed the arrhythmia, and Cedilanid D induced successful conversion. All the other 85 fetuses were with intermittent arrhythmia, normal heart structures, and had no fetal hydrops. After receiving routine treatment, all of them had term deliveries and follow-up monitoring showed normal neonatal heart rhythms (auscultation). CONCLUSIONS: Fetal echocardiography is the main diagnostic tool for prenatal evaluation of fetal arrhythmias. The outcomes of the vast majority of fetal arrhythmias are benign, especially for fetuses with extrasystoles. Their arrhythmias are always well tolerated and disappear during the perinatal period. Fetuses with intermittent arrhythmias without structural heart malformations, fetal hydrops or heart failure, can be followed up with routine prenatal care without the need for special intervention.
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Arritmias Cardíacas/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Coração Fetal/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Ecocardiografia , Ecocardiografia Doppler em Cores , Feminino , Seguimentos , Humanos , GravidezRESUMO
The role of miR-26a in cancer cells seemed controversial in previous studies. Until now, the role of miR-26a in gastric cancer remains undefined. In this study, we found that miR-26a was strongly downregulated in gastric cancer (GC) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of GC. We also found that ectopic expression of miR-26a inhibited GC cell proliferation and GC metastasis in vitro and in vivo. We further identified a novel mechanism of miR-26a to suppress GC growth and metastasis. FGF9 was proved to be a direct target of miR-26a, using luciferase assay and western blot. FGF9 overexpression in miR-26a-expressing cells could rescue invasion and growth defects of miR-26a. In addition, miR-26a expression inversely correlated with FGF9 protein levels in GC. Taken together, our data suggest that miR-26a functions as a tumor suppressor in GC development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for GC.
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Biomarcadores Tumorais/biossíntese , Proliferação de Células , Fator 9 de Crescimento de Fibroblastos/biossíntese , Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , RNA Neoplásico/biossíntese , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Feminino , Fator 9 de Crescimento de Fibroblastos/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas de Neoplasias/genética , RNA Neoplásico/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapiaRESUMO
BACKGROUND: Low tyrosine-protein phosphatase nonreceptor type 12 (PTPN12) expression may be associated with breast cancer growth, proliferation, and metastasis. However, the prognostic value of PTPN12 in breast cancer has not been clearly identified. PATIENTS AND METHODS: 51 triple-negative breast cancer (TNBC) patients and 83 non-TNBC patients with a histopathology diagnosis from October 2001 to September 2006 were included in this study. Immunohistochemical staining for PTPN12 on tissue microarrays was conducted. RESULTS: High PTPN12 expression was seen in 39.2% of TNBC and 60.2 % of non-TNBC cases. Low PTPN12 expression was associated with lymph node status (p = 0.002) and distant metastatic relapse (p = 0.002) in TNBC patients. Similarly, low PTPN12 expression in non-TNBC patients was significantly correlated with lymph node status (p = 0.002), stage (p = 0.002) and distant metastatic relapse (p = 0.039). The high PTPN12 expression group was associated with longer DFS and OS compared with low PTPN12 expression group only in TNBC cases (p = 0.005, p = 0.015), according to univariate Cox regression analysis. CONCLUSION: These findings provide evidence that low expression of PTPN12 is associated with worse prognosis and may be used as a potential prognostic biomarker in TNBC patients.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 12/metabolismo , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Análise Serial de TecidosRESUMO
The number of axillary lymph nodes involved and retrieved are important prognostic factors in breast cancer. The purpose of our study was to investigate whether the lymph node ratio (LNR) is a better prognostic factor in predicting disease-free survival (DFS) for breast cancer patients as compared with pN staging. The analysis was based on 804 breast cancer patients who had underwent axillary lymph node dissection between 1999 and 2008 in Sun Yat-Sen University Cancer Center. Optimal cutoff points of LNR were calculated using X-tile software and validated by bootstrapping. Patients were then divided into three groups (low-, intermediate-, and high-risk) according to the cutoff points. Predicting risk factors for relapse were performed according to Cox proportional hazards analysis. DFS was estimated using the Kaplan-Meier method and compared by the log-rank test. The 5-year DFS rate decreased significantly with increasing LNRs and pN. Univariate analysis found that the pT , pN, LNR, molecule type, HER2, pTNM stage and radiotherapy well classified patients with significantly different prognosis. By multivariate analysis, only LNR classification was retained as an independent prognostic factor. Furthermore, there was a significant prognostic difference among different LNR categories for pN2 category, but no apparent prognostic difference was seen between different pN categories in any LNR category. Therefore, LNR rather than pN staging is preferable in predicting DFS in node positive breast cancer patients, and routine clinical decision-making should take the LNR into consideration.
Assuntos
Neoplasias da Mama/patologia , Intervalo Livre de Doença , Linfonodos/patologia , Recidiva Local de Neoplasia , Adulto , Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Axila , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Estudos de Coortes , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Mastectomia , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos RetrospectivosRESUMO
The aim of the present study was to explore whether ultrasound microbubble destruction augments site-targeted engraftment of bone marrow mesenchymal stem cells (BM-MSCs) to kidney tissue and promotes recovery of the kidney in acute kidney injury (AKI) in rats. AKI was induced by the subcutaneous injection of mercuric chloride (HgCl2). Forty Sprague-Dawley (SD) rats were randomly divided into the following groups after the establishment of rat models of AKI (n = 10): (1) Model group alone (control group); (2) 1.0 W/cm² ultrasound (US) + microbubble (MB) (US/MB group); (3) MSCs group; and (4) 1.0 W/cm² US+MB + MSCs group (US/MB + MSCs group). The number of 4',6-diamidino-2-phenylindole (DAPI) labelled MSCs was evaluated by fluorescence microscopy and real-time polymerase chain reaction (RT-PCR) and Western blotting and histological examination were performed 7 days after MSCs transplantation. It was observed via fluorescence microscopy that the number of DAPI-labelled MSCs in the kidney for the US/MB + MSCs group was significantly more than the MSCs group (p < 0.05). The results from RT-PCR revealed that the US/MB and US/MB + MSCs groups markedly increased the level of inter-cellular adhesion molecule 1 (ICAM-1) messenger ribonucleic acid (mRNA) compared with the control group and the MSCs group (p < 0.05). Western blot analysis showed that the expression of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in the US/MB + MSCs group were markedly increased compared with the all other groups (p < 0.01). The extent of tubular necrosis and dilation was significantly milder in the US/MB + MSCs group (acoustic exposure conditions: 5s at 1 MHz and 1.0 W/cm² with a 5s pause, totalling 60 s) than the all other groups (p < 0.05). Microbubble destruction by 1.0 W/cm² ultrasound can promote both the homing of BM-MSCs to kidney tissue and the recovery of the kidney in AKI in rats.