RESUMEN
Using a prospective, observational cohort study during the post-"dynamic COVID-zero" wave in China, we estimated short-term relative effectiveness against Omicron BA.5 infection of inhaled aerosolized adenovirus type 5-vectored ancestral strain coronavirus disease 2019 (COVID-19) vaccine as a second booster dose approximately 1 year after homologous boosted primary series of inactivated COVID-19 vaccine compared with no second booster. Participants reported nucleic acid or antigen test results weekly until they tested positive or completed predesignated follow-up. After excluding participants infected <14 days after study entry, relative effectiveness among the 6576 participants was 61% in 18- to 59-year-olds and 38% in ≥60-year-olds and was sustained for 12 weeks.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , COVID-19/prevención & control , Estudios Prospectivos , Eficacia de las Vacunas , China/epidemiología , Adenoviridae/genéticaRESUMEN
The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.
Asunto(s)
Antígeno B7-H1 , Quinasa 5 Dependiente de la Ciclina , Inmunoterapia , Fotoquimioterapia , Fotoquimioterapia/métodos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Inmunoterapia/métodos , Animales , Quinasa 5 Dependiente de la Ciclina/metabolismo , Quinasa 5 Dependiente de la Ciclina/antagonistas & inhibidores , Humanos , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Ratones , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Porfirinas/química , Porfirinas/farmacología , Porfirinas/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , ClorofilidasRESUMEN
Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam. The well dispersed NP-Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP-Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL-6 and TNF-α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP-Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.
Asunto(s)
Ciclooxigenasa 2 , Péptidos , Fotoquimioterapia , Fotoquimioterapia/métodos , Ciclooxigenasa 2/metabolismo , Péptidos/química , Péptidos/farmacología , Animales , Humanos , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno/metabolismo , Femenino , Meloxicam/farmacología , Meloxicam/uso terapéutico , Ratones , Protoporfirinas/química , Protoporfirinas/farmacología , Dinoprostona/metabolismoRESUMEN
BACKGROUND: Coarctation of the aorta (CoA) is the most common undiagnosed congenital heart defect during prenatal screening. High false positive and false negative rates seriously affect prenatal consultation and postnatal management. The objective of the study was to assess the utility of various measurements to predict prenatal CoA and to derive a diagnostic algorithm. METHODS: One hundred and fifty-four fetuses with suspected CoA who presented at Fuwai Hospital between December 2017 and August 2021 were enrolled and divided into confirmed CoA cases (n = 47) and false positive cases (n = 107), according to their postnatal outcomes. The transverse aortic arch, isthmus, and descending aorta were measured in the long-axis view of the aortic arch. The angle between the transverse aortic arch (TAO) and the descending aortic arch (DAO) was defined as the TAO-DAO angle and measured in the long axis or sagittal view. Based on the database in GE Voluson E10 and the formula (Z = [Formula: see text]), the standard score (Z-score) of the dimensions of the aorta were calculated in relation to the gestational age. The main echocardiographic indices were combined to design a 3-step diagnostic protocol. The TAO-DAO angle was used as the first step in the diagnostic model. The diameter of the transverse arch and the Z-score of the isthmus were the second step. The third-step indices included a Z-score of the transverse arch, diameter of the isthmus, distance from the left subclavian artery (LSA) to left common carotid artery (LCCA), the ratio of isthmus diameter and LSA diameter and ratio of the distances (the distance between the LSA and LCCA to the distance between the right innominate artery and LCCA). The receiver operating characteristic (ROC) curve determined the predictive capability of each diagnostic parameter, and the kappa test determined the diagnostic accuracy of the proposed model. RESULTS: The cases with confirmed CoA had thinner transverse arches (1.92 ± 0.32 mm vs. 3.06 ± 0.67 mm, P = 0.0001), lower Z-scores of the isthmus (-8.97 ± 1.45 vs. -5.65 ± 1.60, P = 0.0001), smaller TAO-DAO angles (105.54 ± 11.51° vs. 125.29 ± 8.97°, P = 0.0001) and larger distance between the LSA and LCCA (4.45 ± 1.75 mm vs. 2.74 ± 1.07 mm, P = 0.0001) than the false positive cases. The area under the curve (AUC) was 0.947 (95% CI 0.91-0.98) for the TAO-DAO angle ≤ 115.75°, 0.942 (95% CI 0.91-0.98) for the transverse arch diameter ≤ 2.31 mm, 0.937 (95% CI 0.90-0.98) for the Z-score of the isthmus ≤ -7.5, and 0.975 (95% CI 0.95-1.00) for the 3-step diagnostic protocol with 97.8% sensitivity and 97.2% specificity. The kappa test showed that the model's diagnostic accuracy was consistent with postnatal outcomes (kappa value 0.936, P = 0.0001). CONCLUSIONS: The 3-step diagnostic protocol included the three most useful measurements and the additional indices with appropriate cut-off values. The algorithm is useful for the detection of aortic coarctation in fetuses with a high degree of accuracy. TRIAL REGISTRATION: Retrospectively registered.
Asunto(s)
Aorta Torácica , Coartación Aórtica , Ecocardiografía , Ultrasonografía Prenatal , Humanos , Coartación Aórtica/diagnóstico por imagen , Femenino , Embarazo , Aorta Torácica/diagnóstico por imagen , Estudios Retrospectivos , Algoritmos , Edad GestacionalRESUMEN
BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Adulto , Humanos , Preescolar , COVID-19/prevención & control , Estudios Retrospectivos , China/epidemiología , Infecciones AsintomáticasRESUMEN
A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG8 -CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.
RESUMEN
The fictive temperature (Tf ) is widely applied to understand the relaxation thermodynamics of a glass; however, its atomic structural origin is still unclear. Here, we report two novel AZnP3 O9 glasses obtained by melting the composition identical single crystals. These glasses exhibit structural inheritance within 5â Å from the single crystal counterparts that is quantified by δ=nglass /ncry (0≤δ≤1, n is the number of pair correlation functions). Among the available glass-formers, glass KZnP3 O9 exhibits the highest structural inheritance (δ=1, nglass =8). More insightfully, a reverse correlation between δ and the relaxation thermodynamic parameters is observed in glass AZnP3 O9 , revealing for the first time the atomic structural origin of fictive temperature.
RESUMEN
The strong mutual coupling of and even the opposite change in the key parameters, such as the band gap (Eg ) and second-order harmonic generation (SHG), leads to the extreme scarcity in high-performance IR nonlinear optical (NLO) chalcogenides. Herein, we report 8 new sulfides, Na2 Ba[(Agx Na1-x )2 Sn2 S7 ] (1, x=0; 1â series, x=0.1-0.6; Na2 Ba[(Li0.58 Na0.42 )2 Sn2 S7 ], 1-0.6Li); Na2 Sr[Cu2 Sn2 S7 ] (2); and Na2 Ba[Cu2 Sn2 S7 ] (3). We use the structural tolerance factor ( t I e x p ${{t}_{I}^{exp}}$ ) to connect the chemical composition, crystal structure, and NLO properties. Guided by these correlations, a better balance between Eg and SHG is realized in 1, which exhibits a large Eg of 3.42â eV and excellent NLO properties (SHG: 1.5×AGS; laser-induced damage threshold: 12×AGS), representing the best performance among the known Hg- or As-free sulfides to date.
RESUMEN
Recent studies show that intracellular accumulation of cholesterol leads to acquired resistance to gefitinib in non-small cell lung cancer (NSCLC) cells. In this study we investigated how to regulate the cholesterol levels in gefitinib-resistant NSCLC cells. We showed that intracellular cholesterol levels in gefitinib-resistant cell lines (PC-9/GR, H1975, H1650, and A549) were significantly higher than that in gefitinib-sensitive cell line (PC-9). Treatment with gefitinib (5 µM) significantly increased intracellular cholesterol levels in PC-9/GR, H1975, and H1650 cells. Gefitinib treatment downregulated the expression of PPARα, LXRα, and ABCA1, leading to dysregulation of cholesterol efflux pathway. We found that a lipid-lowering drug fenofibrate (20, 40 µM) dose-dependently increased the expression of PPARα, LXRα, and ABCA1, decreased the intracellular cholesterol levels, and enhanced the antiproliferative effects of gefitinib in PC-9/GR, H1975, and H1650 cells. We revealed that fenofibrate increased the gefitinib-induced apoptosis via regulating the key proteins involved in the intrinsic apoptosis pathway. In PC-9/GR, H1975 and H1650 cells, fenofibrate dose-dependently increased the expression of AMPK, FoxO1, and decreased the expression of AKT, which were remarkably weakened by knockdown of PPARα. In PC-9/GR cell xenograft mice, combined administration of gefitinib (25 mg · kg-1 · d-1) and fenofibrate (100 mg · kg-1 · d-1) caused remarkable inhibition on tumor growth as compared to treatment with either drug alone. All the results suggest that fenofibrate relieves acquired resistance to gefitinib in NSCLC by promoting apoptosis via regulating PPARα/AMPK/AKT/FoxO1 pathway. We propose that combination of gefitinib and fenofibrate is a potential strategy for overcoming the gefitinib resistance in NSCLC.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Fenofibrato/farmacología , Gefitinib/farmacología , Hipolipemiantes/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Quinasas Activadas por AMP/metabolismo , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Fenofibrato/química , Proteína Forkhead Box O1/metabolismo , Gefitinib/química , Humanos , Hipolipemiantes/química , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Estructura Molecular , PPAR alfa/agonistas , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Relación Estructura-ActividadRESUMEN
Non-linear optical chalcogenides with a wide band gap (Eg ) and excellent NLO properties are key materials for highly desirable multiwaveband tunable optical parametric oscillators (OPOs). We exploit the "electronic structure engineer bucket effect" to develop a novel dual-waveband SrZnGeS4 with an ultrawide transparency window. It exhibits an asymmetric Fdd2 structure that consists of layers formed by corner-sharing [ZnGeS6 ] dimers. SrZnGeS4 is transparent from 0.30 to 23.6â µm, spanning the UV-, vis-, mid- and far-IR spectral regions and has the widest Eg (3.63â eV) in the AeMII MIV Q4 family to date. It exhibits phase matching, high SHG intensities (e.g., 11.0×KDP and 17.5×AGS under λinc =1450 and 950â nm, respectively), and a very high laser-induced damage threshold (35×AGS). These results not only suggest bright prospects for high-power laser applications but may also enable applications of the multiwaveband OPO system from the UV-visible to far-IR regions.
RESUMEN
Objective: To assess the effectiveness of non-pharmacological interventions for seniors with depressive symptoms.Methods: A comprehensive literature search was performed. We conducted network meta-analysis in two ways, intervention classes (psychosocial, psychotherapy, physical activity, combined, treatment as usual) and individual intervention (11 categories). Whenever included studies used different scales, the different instruments were converted to the units of the scale most frequently used (the Geriatric Depression Scale), such that the effect size was reported as a mean difference (MD) with 95% confidence interval (CI). The risk of bias of RCTs included in this review was assessed according to the Cochrane Handbook. Bayesian NMA was conducted using R-3.4.0 software.Results: A total of 35 RCTs with 3,797 enrolled patients were included. Compared to conventional treatment, physical activity and psychotherapy resulted in significant improvements in depressive symptoms (MD: 2.25, 95%CrI: 0.99-3.56; SUCRA = 86.07%; MD: 1.75, 95% CrI: 0.90-2.64; SUCRA = 66.44%, respectively). Similar results were obtained for music (MD: 2.6; 95% CrI: 0.84-4.35;SUCRA = 80.53%), life review (MD:1.92; 95% CrI:0.71-3.14; SUCRA = 65.62%), cognitive behavioral therapy (MD: 1.27; 95% CrI: 0.23-2.38; SUCRA = 45.4%), aerobic (MD: 1.84; 95% CrI: 0.39-3.36; SUCRA = 63%) and resistance training (MD: 1.72; 95% CrI: 0.06-3.42; SUCRA = 59.24%). Network meta-regression showed that there were no statistically significant subgroup effects.Conclusions: Physical activity and psychotherapy demonstrated statistically significant superiority over conventional treatment. Music and life review therapy proved the most promising individual interventions. However, conclusions are limited by the lack of sufficient sample size and consensus regarding intervention categories and so an adequately powered study is necessary to consolidate these findings.
Asunto(s)
Depresión , Psicoterapia , Anciano , Teorema de Bayes , Depresión/terapia , Humanos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Drought is one of the most important environmental factors limiting plant growth and productivity. The molecular mechanisms underlying plant drought resistance are complex and not yet fully understood. Here, we show that the Arabidopsis MADS-box transcription factor AGL16 acts as a negative regulator in drought resistance by regulating stomatal density and movement. Loss-of-AGL16 mutants were more resistant to drought stress and had higher relative water content, which was attributed to lower leaf stomatal density and more sensitive stomatal closure due to higher leaf ABA levels compared with the wild type. AGL16-overexpressing lines displayed the opposite phenotypes. AGL16 is preferentially expressed in guard cells and down-regulated in response to drought stress. The expression of CYP707A3 and AAO3 in ABA metabolism and SDD1 in stomatal development was altered in agl16 and overexpression lines, making them potential targets of AGL16. Using chromatin immunoprecipitation, transient transactivation, yeast one-hybrid, and electrophoretic mobility shift assays, we demonstrated that AGL16 was able to bind the CArG motifs in the promoters of the CYP707A3, AAO3, and SDD1 and regulate their transcription, leading to altered leaf stomatal density and ABA levels. Taking our findings together, AGL16 acts as a negative regulator of drought resistance by modulating leaf stomatal density and ABA accumulation.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sequías , Regulación de la Expresión Génica de las Plantas , Estomas de Plantas/metabolismoRESUMEN
5-HT plays a crucial role in the progress and adjustment of pain both centrally and peripherally. The therapeutic action of the 5-HT receptors` agonist and antagonist in neuropathic pain have been widely reported in many studies. However, the specific roles of 5-HT subtype receptors have not been reviewed comprehensively. Therefore, we summarized the recent findings on multiple subtypes of 5-HT receptors in both central and peripheral nervous system in neuropathic pain, particularly, 5-HT1, 5-HT2, 5-HT3 and 5-HT7 receptors. In addition, 5-HT4, 5-HT5 and 5-HT6 receptors were also reviewed. Most of studies focused on the function of 5-HT subtype receptors in spinal level compared to brain areas. Based on these evidences, the pain process can be facilitated or inhibited that depending on the specific subtypes and the distribution of 5-HT receptors. Therefore, this review may provide potential therapeutic implications in treatment of neuropathic pain.
Asunto(s)
Encéfalo/metabolismo , Neuralgia/metabolismo , Umbral del Dolor , Receptores de Serotonina/metabolismo , Serotonina/metabolismo , Médula Espinal/metabolismo , Analgésicos/uso terapéutico , Animales , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Humanos , Neuralgia/tratamiento farmacológico , Neuralgia/fisiopatología , Umbral del Dolor/efectos de los fármacos , Receptores de Serotonina/efectos de los fármacos , Serotoninérgicos/uso terapéutico , Transducción de Señal , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiopatologíaRESUMEN
A 3D lanthanide coordination polymer {[La(SIP)(H2O)3]·H2O}n (La-MOF) was synthesized successfully by the solvothermal reaction of La(NO3)3·6H2O and 5-sulfoisophthalic acid monosodium salt (NaH2SIP). In particular, two oxygen atoms of sulfate participate in the coordination, which is unusual in all the complexes. La-MOF was characterized by single-crystal X-ray diffraction, IR spectroscopy, powder X-ray diffraction, thermal-gravimetric analysis, and X-ray photoelectron spectroscopy. La-MOF shows excellent water stability and chemical stability in a broad pH range from 2 to 13. Moreover, the fluorescence and sensing properties of La-MOF were invsetigated in detail via its titration and cycling processes, revealing its highly efficient and selective quenching responses and good recyclability for the detection of Fe3+, Cr2O72- and CrO42- ions. In addition, La-MOF possesses an outstanding specific capacitance of 213 F g-1 at 0.5 A g-1. It still retains 92% of the original capacitance after 2000 cycles, exhibiting remarkable long-term cycling stability and reversibility; therefore, the electrode material based on La-MOF is a competitive and promising candidate for application in supercapacitors.
RESUMEN
OBJECTIVES: To explore the independent associations of sedentary behavior and physical activity with telomere length among Chinese adults. METHODS: Data on total time of sedentary behavior, screen-based sedentary behavior (including television watching and computer or phone use), moderate to vigorous physical activity, and dietary intake of 518 adults in Chengdu, Guizhou, and Xiamen in China (54.25% women) aged 20 to 70 years were obtained between 2013 and 2015 through questionnaires. Height, weight, and waist circumference were measured to calculate body mass index and percentage of body fat. Telomere length was measured through Southern blot technique. RESULTS: Television watching was inversely related to adjusted telomere length (-71.75 base pair; SE = 34.40; P = .04). Furthermore, a similar trend between telomere length and television watching was found in the group aged 20 to 40 years after adjusting for all covariates. Adults aged 20 to 40 years in the highest tertile of daily time spent on watching television had 4.0% shorter telomere length than adults in the lowest tertile (P = .03). CONCLUSIONS: Although the association is modest, television watching is inversely related to telomere length among Chinese adults, warranting further investigation in large prospective studies.
Asunto(s)
Conducta Sedentaria , Televisión/estadística & datos numéricos , Telómero/genética , Adulto , Anciano , Índice de Masa Corporal , China , Ejercicio Físico/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Oridonin (ORI) can inhibit proliferation and migration in various types of cancer cell lines. However, the exact mechanism remains unclear. We investigated the migration inhibitory effect of ORI on human pancreatic cancer SW1990 cells and dissected the possible molecular mechanism(s). METHODS: CCK-8 assay was used to observe the cell viability. Wound healing assay, transwell assay and spontaneous metastasis model were used to observe the migration activities. Real-time PCR, immunofluorescence, western blot analysis and immunohistochemistry methods were used to observe the expression of genes or proteins. RESULTS: ORI inhibited the migration of SW1990 cells. Real-time PCR and immuno-fluorescence analyses of epithelial-to-mesenchymal transition (EMT) markers were compared between control group and ORI group. The expression of mesenchymal molecular markers, such as vimentin, snail and slug decreased. The expression of epithelial-related marker E-cadherin increased. Wnt/ß-catenin signalling was inhibited by ORI using luciferase reporter assay. ORI can decrease the ß-catenin protein level not only in the nucleus, but also in the cytoplasm and the whole cell after the treatment with ORI and glycogen synthase kinase 3ß (GSK3ß) was increased in the ORI-treated group. CHIR could attenuate the effects of ORI in SW1990 cells. We established a mice model by injecting 1 × 10(6) SW1990 cells into nude mice intraperitoneally to test whether ORI affects tumour metastasis. Metastatic formation was inhibited by ORI (5 and 10 mg/kg) compared with the control group. Tumour sections stained with anti-E-cadherin, anti-vimentin and anti-ß-catenin antibodies revealed that ORI inhibited EMT, as well as the Wnt/ß-catenin pathway in vivo. CONCLUSIONS: ORI can inhibit pancreatic cancer cell SW1990 migration and EMT by down-regulating Wnt/ß-catenin signal transduction in vitro and in vivo. Therefore, it can be potentially and effectively used in the clinical management of pancreatic cancer.
RESUMEN
A Gram-stain-negative, facultatively anaerobic, non-motile and pink-pigmented bacterium, designated strain HF08(T), was isolated from marine sediment of the coast of Weihai, China. Cells were rod-shaped, and oxidase- and catalase-positive. The isolate grew optimally at 33 °C, at pH 7.5-8.0 and with 2-3% (w/v) NaCl. The dominant cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0 and iso-C14 : 0. Menaquinone 7 (MK-7) was the major respiratory quinone and the DNA G+C content was 44.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate was a member of the class Bacteroidia, and shared 88-90% sequence similarity with the closest genera Sunxiuqinia, Prolixibacter, Draconibacterium, Mariniphaga and Meniscus. Based on the phylogenetic and phenotypic evidence presented, a novel species in a new genus of the family Prolixibacteraceae is proposed, with the name Roseimarinus sediminis gen. nov., sp. nov. The type strain of Roseimarinus sediminis is HF08(T) ( = KCTC 42261(T) = CICC 10901(T)).
Asunto(s)
Bacteroidetes/clasificación , Sedimentos Geológicos/microbiología , Filogenia , Técnicas de Tipificación Bacteriana , Bacteroidetes/genética , Bacteroidetes/aislamiento & purificación , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Datos de Secuencia Molecular , Pigmentación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
A novel Gram-stain-negative, rod-shaped, gliding, facultatively anaerobic, oxidase-negative and catalase-positive bacterium, designated FA350(T), was isolated from coastal sediment from Xiaoshi Island, Weihai, China. Strain FA350(T) showed growth on modified nutrient agar supplemented with 0.1% d-(+)-trehalose and with distilled water replaced by seawater. Optimal growth occurred at 33 °C and pH 8.5 with 4% NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain FA350(T) belongs to a novel bacterial order in the class Deltaproteobacteria , and the most closely related type strains belong to the order Desulfuromonadales , with 85.1-85.6% 16S rRNA gene sequence similarity. The polar lipid profile of the novel strain consisted of phosphatidylethanolamine, phosphatidylglycerol and two unknown phospholipids. Major cellular fatty acids were iso-C15 : 0, iso-C17 : 0 and iso-C17 : 1ω10c and menaquinone MK-7 was the sole respiratory quinone. The DNA G+C content of strain FA350(T) was 60.3 mol%. The isolate and closely related environmental clones formed a novel order-level clade in the class Deltaproteobacteria . Comparative analysis of 16S rRNA gene sequences and characterization indicated that strain FA350(T) may represent a novel order of the Deltaproteobacteria . Here, we propose the name Bradymonas sediminis gen. nov., sp. nov. to accommodate strain FA350(T). The type strain of Bradymonas sediminis is FA350(T) (â=DSM 28820(T)â=CICC 10904(T)); Bradymonadales ord. nov. and Bradymonadaceae fam. nov. are also proposed to accommodate the novel taxon.
Asunto(s)
Deltaproteobacteria/clasificación , Sedimentos Geológicos/microbiología , Filogenia , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Deltaproteobacteria/genética , Deltaproteobacteria/aislamiento & purificación , Ácidos Grasos/química , Islas , Datos de Secuencia Molecular , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
Strain FA028T, a beige-pigmented, facultatively anaerobic, heterotrophic, catalase-negative and oxidase-positive, Gram-stain-negative bacterium, was isolated from marine sediment of the coast of Weihai, China. Cells of strain FA028T were rod-shaped, 13 µm in length and 0.5 µm in width. The strain was able to grow at 1337 °C, at pH 7.09.5 and in the presence of 1.04.0 % (w/v) NaCl. Optimal growth was observed at 28 °C, with 3.0 % NaCl and at pH 7.58.0. Nitrate was not reduced. The G+C content of the DNA was 43.4âmol%. The isoprenoid quinone was Q-9 and the main cellular fatty acids (>10 %) were C16 : 0, C16 : 1ω9c and iso-C15 : 0 2-OH/C16 : 1ω7c. The major polar lipids in strain FA028T were phosphatidylglycerol, phosphatidylethanolamine and diphosphatidylglycerol; phospholipid was present in moderate to minor amounts in the polar lipid profile. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain FA028T was affiliated with the phylum Proteobacteria. 16S rRNA gene sequence comparisons showed that this isolate is unique, sharing < 93 % similarity with species of the families Alteromonadaceae and Oceanospirillaceae. On the basis of the phenotypic and phylogenetic data, strain FA028T should be classified as representing a novel species of a new genus within the family Alteromonadaceae, for which the name Alkalimarinus sediminis gen. nov., sp. nov. is proposed. The type strain of Alkalimarinus sediminis is FA028T ( = CICC 10906T = KCTC 42258T).
Asunto(s)
Alteromonadaceae/clasificación , Sedimentos Geológicos/microbiología , Filogenia , Agua de Mar/microbiología , Alteromonadaceae/genética , Alteromonadaceae/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Datos de Secuencia Molecular , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
A novel bacterial strain, designated Y11T, was isolated from marine sediment at Weihai in China. Comparative analysis of 16S rRNA gene sequences demonstrated that the novel isolate showed highest similarity to Saccharicrinis fermentans DSM 9555T (94.0 %) and Saccharicrinis carchari SS12T (92.7 %). Strain Y11T was a Gram-stain-negative, rod-shaped, non-endospore-forming, yellow-pigmented bacterium and was able to hydrolyse agar weakly. It was catalase-negative, oxidase-positive, facultatively anaerobic and motile by gliding. Optimal growth occurred at 28-30 °C, at pH 7.0-7.5 and in the presence of 2-3 % (w/v) NaCl. The DNA G+C content was 34.4âmol%. The strain contained MK-7 as the prevalent menaquinone. The major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0 and C15 : 1ω6c. The predominant polar lipids were phosphatidylethanolamine and two unknown lipids. Data from the present polyphasic taxonomic study clearly place the strain as representing a novel species within the genus Saccharicrinis, for which the name Saccharicrinis marinus sp. nov. is proposed. The type strain is Y11T ( = CICC10837T = KCTC42400T).