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INTRODUCTION/AIMS: Easy fatigability, the clinical hallmark of generalized myasthenia gravis (GMG), cannot be detected in a dynamic way. The aim of this study was to assess respiratory function dynamically through diaphragmatic ultrasonography (DUS) in GMG patients. METHODS: GMG patients and controls were recruited in a 1:1 ratio. DUS was performed during one quiet breath and 15 consecutive deep breaths. The diaphragm thicknesses were measured at different positions. Diaphragm thickening fraction (TFdi) and the maximal change in diaphragm thickness (Tmax) during 15 consecutive deep breaths were calculated and transformed to normality, named N-TFdi and N-Tmax, respectively. The percentages of changes in TFdi and Tmax compared with baseline were named ΔTFdi and ΔTmax, respectively. The diagnostic parameter for respiratory muscle fatigue was chosen from ΔTFdi and ΔTmax at different deep breath times according to their ability to distinguish GMG patients from controls and the interrater reliability of TFdi and Tmax. RESULTS: Thirty-four GMG patients and 30 healthy controls were enrolled. N-TFdi and N-Tmax significantly changed as the number of deep breaths increased (p < .001) in GMG patients, but not in controls. ΔTmax of the 15th deep breath (ΔTmax15) was selected as the diagnostic parameter for respiratory muscle fatigue. There were no significant differences in percentage of predicted values of forced vital capacity and arterial partial pressure of carbon dioxide between patients with normal and abnormal ΔTmax15. DISCUSSION: DUS could identify diaphragm fatiguability in GMG patients, which may be more reliable and sensitive in assessment of diaphragm fatigue than conventional methods.
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Diafragma , Miastenia Gravis , Humanos , Reproducibilidad de los Resultados , Miastenia Gravis/complicaciones , Miastenia Gravis/diagnóstico por imagen , Capacidad Vital , Ultrasonografía/métodosRESUMEN
OBJECTIVE: Most studies investigated the relationship between COVID-19 and Guillain-Barré syndrome (GBS) by comparing the incidence of GBS before and during the pandemic of COVID-19. However, the findings were inconsistent, probably owing to varying degrees of the lockdown policy. The quarantine requirements and travel restrictions in China were lifted around December 7, 2022. This study aimed to explore whether the relative frequency of GBS increased during the major outbreak in the absence of COVID-19-mandated social restrictions in China. METHODS: GBS patients admitted to the First Hospital, Shanxi Medical University, from December 7, 2022 to February 20, 2023, and from June, 2017 to August, 2019 were included. The relative frequencies of GBS in hospitalized patients during different periods were compared. The patients with and without SARS-CoV-2 infection within six weeks prior to GBS onset formed the COVID-GBS group and non-COVID-GBS group, respectively. RESULTS: The relative frequency of GBS among hospitalized patients during the major outbreak of COVID-19 (13/14,408) was significantly higher than that before the COVID-19 epidemic (29/160,669, P < 0.001). More COVID-GBS patients (11/13) presented AIDP subtype than non-COVID-GBS cases (10/27, P = 0.003). The mean interval between onset of infective symptoms and GBS was longer in COVID-GBS (21.54 ± 11.56 days) than in non-COVID-GBS (5.76 ± 3.18 days, P < 0.001). CONCLUSIONS: COVID-19 significantly increased the incidence of GBS. Most COVID-GBS patients fell into the category of AIDP, responded well to IVIg, and had a favorable prognosis.
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COVID-19 , Síndrome de Guillain-Barré , SARS-CoV-2 , Humanos , Síndrome de Guillain-Barré/epidemiología , COVID-19/epidemiología , China/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Incidencia , Anciano , Hospitalización/estadística & datos numéricos , Adulto Joven , Pandemias , AdolescenteRESUMEN
INTRODUCTION/AIMS: Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) is an autosomal recessive disease chiefly caused by variants of ETFDH affecting fatty acid metabolism. In our cohort, hyperhomocysteinemia (HHcy) was common. In this study we aimed to identify the association between RR-MADD and HHcy. METHODS: We performed a retrospective review of 13 patients with RR-MADD. Thirty-three healthy controls were recruited, and logistic regression was used to investigate the association between RR-MADD and HHcy. Muscle tissues from six patients and six controls without myopathies were collected to measure the levels of flavin adenine dinucleotide (FAD), an active form of riboflavin. Whole-exome sequencing was performed to identify the disease-associated variants. RESULTS: The RR-MADD patients had a higher prevalence of HHcy (9 of 12) than controls (6 of 33, P < .001). In the multivariate analysis, RR-MADD was positively related to HHcy (P = .014). Muscular FAD levels were decreased in RR-MADD patients (P = .006). Thirteen variants (8 reported and 5 novel) were identified in ETFDH. Of these, c.250G > A was the most common pathogenic variant with an allelic frequency of 4 of 20. DISCUSSION: HHcy was associated with RR-MADD and may aid in the diagnosis of the disease. Our findings expand the mutational spectrum of RR-MADD.
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Objective: A new aldehyde-free fixative has been developed and its effect has been compared to traditional formaldehyde fixative in terms of the fixation effect and HE staining of the heart, liver, lung, and kidney. The air in the experimental area was examined to evaluate its impact on the environment and human health. Methods: The organs from mice of groups 1-6 were taken respectively (thickness of liver and lung was 3 mm). After the heart and kidney capsule were removed, the organs were longitudinally cut along their maximum surface, and half was taken. Thereafter, the tissue fixation effect was observed by Hematein and Eosin (Hï¼E) staining and the total protein content of tissue was examined by the ultramicro spectrophotometer. Additionally, the volatility ratio of the new fixative and the traditional formaldehyde is compared. Result: The results showed that there was no significant difference between the fixation effect of the new aldehyde-free fixation and the traditional formaldehyde fixative on mouse organs and the air quality in the experimental area was found to be significantly better when the new aldehyde-free fixative is used than when the traditional formaldehyde fixative is used. Conclusion: Traditional formaldehyde fixative in HE staining can be replaced by the new environment-friendly formaldehyde-free fixative, however further special staining of fixed tissue and immunohistochemical studies are needed.
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BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin condition; however, little is known about the pathogenesis and serum biomarker of this disease. METHODS: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic assay was adopted to identify and quantify the differentially expressed proteins (DEPs) in the serum of AD patients. Bioinformatic analysis, including GO, Reactome, GSEA, PPI, and ssGSEA analysis, were used to identified the enriched pathways, hub proteins and immune cells. The expression level and distribution of hub proteins were confirmed by ELISA and IHC. RESULTS: Sixty-six DEPs were identified with iTRAQ proteomic assay by analyzing serum from AD patients and normal subjects. GO and Reactome analysis shown the alternated pathway were mainly involved in immunity, oxidative stress, and actin cytoskeleton. The GSEA and PPI network analysis among the DEPs were carried out and identified Cofilin-1 and profilin-1 as the core components of this network. Additionally, the disruption of Th1/Th2/Th17 cell balance and the significantly reducing of Treg, MDSC, and γδT cells was also found in AD patients using the ssGSEA analysis. Further ELISA and IHC assay validated the significantly elevated expression of Cofilin-1 in AD patients. CONCLUSION: Our results suggested that Cofilin-1 may serve as a novel biomarker for AD diagnosis.
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Dermatitis Atópica , Proteómica , Humanos , Proteómica/métodos , Dermatitis Atópica/diagnóstico , Recurrencia Local de Neoplasia , Biomarcadores , Células Th17/patologíaRESUMEN
BACKGROUND: Guillain-Barré Syndrome (GBS) is caused by immunoglobulin G (IgG) autoantibodies. Efgartigimod, a human IgG antibody Fc fragment that acts as a natural ligand for the FcRn, can increase IgG degradation, which thus may be a promising therapeutic drug for GBS. CASE PRESENTATION: The two patients presented with postinfectious and acute flaccid paralysis. On admission, they were bedridden. Nerve conduction studies indicated peripheral neuropathy. GBS was suspected and they are treated with two doses of efgartigimod (10 mg/kg) within 5 days. Their muscle strength improved gradually and 4 weeks after the initial dose, they could walk independently. Following the first dose, Patient 1 complaint of muscle soreness, which subsided the next morning. Patient 2 was intubated due to respiratory failure the day after the initial dose, and did not report other adverse effects. DISCUSSION: In GBS patients, two doses of efgartigimod (10 mg/kg) were effective in rapidly improving muscle strength, with a satisfactory safety profile. The findings suggest a potential role for efgartigimod in modifying the disease process in GBS patients. CONCLUSION: Efgartigimod seems effective and safe in the treatment of GBS. This study indicates the potential role of efgartigimod as a novel treatment option for GBS. Well-designed clinical trials should be conducted.
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Síndrome de Guillain-Barré , Humanos , Síndrome de Guillain-Barré/tratamiento farmacológico , Síndrome de Guillain-Barré/fisiopatología , Masculino , Persona de Mediana Edad , Adulto , Femenino , Resultado del TratamientoRESUMEN
BACKGROUND: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known whether late-onset MADD affects men and women equally. METHODS: In this systematic review and meta-analysis, the PubMed, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched until 01/08/2023. Studies reporting sex distribution in patients with late-onset MADD were included. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Pre-specified outcomes of interest were the male-to-female ratio (MFR) of patients with late-onset MADD, the differences of clinical characteristics between the sexes, and factors influencing the MFR. RESULTS: Of 3379 identified studies, 34 met inclusion criteria, yielding a total of 609 late-onset MADD patients. The overall pooled percentage of males was 58% (95% CI, 54-63%) with low heterogeneity across studies (I2 = 2.99%; P = 0.42). The mean onset ages, diagnostic delay, serum creatine kinase (CK), and allelic frequencies of 3 hotspot variants in ETFDH gene were similar between male and female patients (P > 0.05). Meta-regressions revealed that ethnic group was associated with the MFR in late-onset MADD, and subgroup meta-analyses demonstrated that East-Asian patients had a higher percentage of male, lower CK, and higher proportion of hotspot variants in ETFDH gene than non-East-Asian patients (P < 0.05). CONCLUSIONS: Male patients with late-onset MADD were more common than female patients. Ethnicity was proved to be a factor influencing the MFR in late-onset MADD. These findings suggest that male sex may be a risk factor for the disease.
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Proteínas Hierro-Azufre , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH , Humanos , Masculino , Femenino , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/genética , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/diagnóstico , Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa/metabolismo , Mutación , Diagnóstico Tardío , Flavoproteínas Transportadoras de Electrones/genética , Proteínas Hierro-Azufre/genética , Proteínas Hierro-Azufre/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/metabolismo , Acil-CoA Deshidrogenasa/genética , Acil-CoA Deshidrogenasa/metabolismoRESUMEN
OBJECTIVE: This study aimed to establish and validate a nomogram prognostic model for predicting short-term efficacy of acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (GMG). METHODS: A retrospective observational study was conducted at the First Hospital of Shanxi Medical University, enrolling patients diagnosed with AChR-Ab+ GMG from May 2020 to September 2022. The primary outcome was the change in the Myasthenia Gravis Foundation of America (MGFA) post-intervention status after 6 months of standard treatment. Predictive factors were identified through univariate and multivariate logistic regression analyses, with significant factors incorporated into the nomogram. The bootstrap test was used for internal validation of the nomogram model. Model performance was assessed using calibration curves, receiver-operating characteristic curve analysis, and decision curve analysis (DCA). RESULTS: A total of 90 patients were enrolled, of whom 30 achieved unchanged or worse status after 6 months of standard therapy. Univariate logistic regression analysis showed that quantitative myasthenia gravis score, gender, body mass index, course of disease, hemoglobin levels, and white blood cell counts were six potential predictors. These factors were used for multivariate logistic regression analysis, and a nomogram was constructed. The calibration curve showed that the predicted value was in good agreement with the actual value (p = 0.707), and the area under the curve value (0.792, 95% CI 0.686-0.899) indicated good discrimination ability. DCA suggests that this model has potential clinical application value. CONCLUSION: The constructed nomogram, based on key patient indicators, shows promise as a clinically useful tool for predicting the short-term efficacy of treatment of AChR-Ab+ GMG. Validation in larger, multicenter cohorts is needed to further substantiate its applicability.
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Developing durable photocatalysts with highly efficient antibiotics degradation is crucial for environment purification. Herein, tetra (4-carboxyphenyl) porphyrin (TCPP) was loaded onto the surface of Bi2MoO6 microspheres to gain hierarchical organic-inorganic TCPP/Bi2MoO6 (TCPP/BMO) heterojunctions via a facile impregnation strategy. The catalytic properties of these catalysts were comprehensively investigated through the photodegradation of tetracycline hydrochloride (TC) under visible light. Among all the TCPP/BMO heterojunctions, the highest photodegradation rate constant (0.0278â¯min-1) was achieved with 0.25â¯wt% TCPP (TCPP/BMO-2), which was approximately 1.15 folds greater than that of pristine Bi2MoO6 and far superior to pure TCPP. The extremely high photocatalytic performance is attributed to the interfacial interaction between TCPP and Bi2MoO6, which favors the efficient separation of charge carriers and the enhancement of visible-light absorbance. TCPP/BMO-2 possesses high mineralization capability and good recycling performance. Photo-induced O2-, h+, and OH were mainly responsible for the degradation of TC. The degradation pathways of TC and toxicity of degradation intermediates were analyzed based on the intermediates detected by the high performance liquid chromatography-mass spectrometer (HPLC-MS) and the toxicity assessment by the quantitative structure-activity relationship (QSAR) prediction. A possible photocatalytic mechanism over TCPP/BMO is proposed. This work offers an insight in developing the porphyrin-based organic-inorganic heterojunctions for effectively remedying pharmaceutical wastewater.
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Porfirinas , Tetraciclina , Antibacterianos/farmacología , Bismuto , MolibdenoRESUMEN
OBJECTIVE: To study the effect of cadmium ions of different concentrations on gastrointestinal epithelial cells structure of Pheretima aspegillum (PA). METHODS: PA were contaminated with cadmium ions of different concentrations,and the structure of the body skin was observed, under light microscope and transmission electron microscope. RESULTS: With the increasing of cadmium ions concentration, a large number of lysosomal hyperplasia could be seen in the PA intestinal epithelial cells, the Golgi complex distributed around, and some Golgi complex hyperplasiaed, extended to a large bubble, microvilli, cilia arranged in irregular, disordered. While in the group contaminated with the high concentration cadmium ions, such as 30 mg/kg, the microvilli of the PA intestinal epithelial cells contracted, necrotic ulcer lesions occurred in the ciliated cells. CONCLUSION: The ultrastructure damage extent of PA gastrointestinal epithelial cells is dependent on the amount of the heavy metal contamination. PA with lower concentration Cd contamination shows mainly lysosomal proliferation, indicating heavy metal accumulation in lysosomes to eliminate toxic substances as a responsible reaction, this kind of damage is reversible. However, PA with higher concentration Cd contamination shows mainly microvilli and mitochondrial damage, nuclear membrane disintegration, nucleoplasm spillover, leading to necrosis, irreversible damage, indicating heavy metal accumulation of PA is related to this trait of intestinal epithelial cells.
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Cadmio/toxicidad , Células Epiteliales/patología , Oligoquetos , Contaminantes del Suelo/toxicidad , Animales , Cadmio/metabolismo , Células Epiteliales/ultraestructura , Mucosa Intestinal/citología , Mucosa Intestinal/patología , Mucosa Intestinal/ultraestructura , Microscopía Electrónica de Rastreo , Contaminantes del Suelo/metabolismoRESUMEN
Small cell lung cancer (SCLC) is a neuroendocrine tumor with fast progression, high malignancy, easy recurrence, and extremely poor prognosis. In the past 30 years, the clinical treatment strategy of SCLC has been mainly chemotherapy and radiotherapy, but the curative effect is not significant; the current immunotherapy of SCLC has gradually entered the clinic and has made certain progress. Tumor immunotherapy includes immune checkpoint inhibitors, tumor vaccines, cytokines, chimeric antigen receptor T-cell immunotherapy (CAR-T) therapy, etc. Currently, immune checkpoint inhibitors are the most widely used. This article summarizes the principles of immune checkpoint inhibitors and related drugs, summarizes their domestic and foreign clinical trials progress in SCLC treatment, reviews the biomarkers used in the therapy, and discusses its future development direction.â©.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Vacunas contra el Cáncer/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológicoRESUMEN
Marine biofouling can cause a biocorrosion, resulting in degradation and failure of materials and structures. In order to prevent sea creatures from attaching to the surface, in this work, a new environmentally friendly antifouling coating by incorporating antibacterial polymers and natural antifouling agents has been designed and synthesized. Surface chemical composition and changes in surface hydrophobicity were studied by FTIR spectroscopy and contact angle measurements, respectively. Measurements of mass loss of antifouling resin were also carried out and the release rate of camphor from antifouling coating was tested by using UPLC. It had been found that the changes in the content of triisopropylsilylacrylate (TIPSA) (from 4% to 12%) and isobornyl methacrylate (IBOMA) (from 50% to 16.7%) did not significantly affect the release of camphor. The content of IBOMA decreased from 50% to 16.7%, the antifouling performance of the resin system appeared slightly reduced. In addition, rosin could help regulate the release rate of the resin system to desorb camphor slowly in water in a controlled manner. Furthermore, the antifouling capability of as-prepared samples was evaluated via algae suppression experiments and marine field tests. This study highlighted the environmentally friendly antifouling coating as a potential candidate and efficient strategy to prohibit biofouling in seawater.
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BACKGROUND AND OBJECTIVES: Since December 2019, the rapid epidemic spread of COVID-19 in China has aroused the attention of the government and the public. The purpose of this study is to investigate the attitude and knowledge among medical students and non-medical students toward SARS-CoV-2 infection. METHODS: A web-based survey was disseminated to the students from medical colleges and comprehensive universities via the survey website (www.wjx.cn) and via WeChat. Participation in the study was voluntary with the instruction to click on the website or scan the QR code to complete the anonymous electronic questionnaire from February 5 to 7, 2020. RESULTS: The questionnaire was completed by 588 students from 20 colleges and universities in China. Of the respondents, 66.0% were medical students and 34.0% were non-medical students. 99.6 % of the students held an optimistic attitude toward the COVID-19 epidemic situation. The majority of participants had a good level of knowledge of common symptoms, transmission, and prevention of the disease. In a comparison between non-medical students with medical students, the medical students had a deeper understanding of COVID-19. In this study, we also found that female students had a better understanding of transmission and prevention than male students did. CONCLUSIONS: The majority of students who participated in the questionnaire had a positive attitude and a good perception about COVID-19.
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Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Conocimientos, Actitudes y Práctica en Salud , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , Estudiantes de Medicina/psicología , Universidades , Betacoronavirus , COVID-19 , China , Infecciones por Coronavirus/complicaciones , Estudios Transversales , Femenino , Humanos , Masculino , Neumonía Viral/complicaciones , SARS-CoV-2 , Factores Sexuales , Encuestas y CuestionariosRESUMEN
Novel 3D flower-like Ag/AgCl/BiOCOOH ternary heterojunction photocatalysts were fabricated by the solvothermal and in-situ precipitation methods, followed by light reduction treatment. The Ag/AgCl nanoparticles were homogeneously distributed on 3D BiOCOOH microspheres. These obtained catalysts were characterized by XRD, SEM, TEM, diffuse reflectance spectra (DRS), and photoluminescence (PL). As expected, they exhibited extraordinary photocatalytic capabilities for the elimination of rhodamine B (RhB) and ciprofloxacin (CIP) under simulated sunlight, the results revealed that the Ag/AgCl/BiOCH-3 with 20 wt.% of Ag/AgCl possessed the maximum activity, and the rate constant for the RhB degradation reached up to 0.1353 min-1, which was about 16.5 or 12.2 times that of bare BiOCOOH or Ag/AgCl. The PL characterization further verified that Ag/AgCl/BiOCOOH heterojunctions were endowed with the effective separation of photogenerated carriers. The excellent photocatalytic ability of Ag/AgCl/BiOCOOH could be credited to the synergistic interactions between Ag/AgCl and BiOCOOH, which not only substantially widened the light absorption, but also evidently hindered the charge recombination. The trapping experiments revealed that the dominant reactive species in RhB removal were h+, â¢OH, and â¢O2- species. In addition, Ag/AgCl/BiOCOOH was quite stable and easily recyclable after multiple cycles. The above results imply that the 3D flower-like Ag/AgCl/BiOCOOH ternary heterojunction photocatalyst holds promising prospects in treating industrial wastewater.
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In this work, the role of long period stacking ordered (LPSO) phase in the crack propagation behavior of an as-cast Mg95.5Y3Zn1.5 alloy was investigated by dynamic four-point bent tests. The as-cast Mg95.5Y3Zn1.5 alloy is mainly composed of Mg matrix, 18R LPSO phase located at the grain boundaries and 14H LPSO phase located within the Mg matrix. The alloy exhibits excellent dynamic mechanical properties; the yield stress, maximum stress and strain to failure are 190.51 ± 3.52 MPa, 378.32 ± 4.26 MPa and 0.168 ± 0.006, respectively, at the strain rate of ~3000 s-1. The LPSO phase effectively hinders dynamic crack propagation in four typical ways, including crack tip blunting, crack opening inhibition, crack deflection and crack bridging, which are beneficial to the mechanical properties of the alloy under dynamic loadings.
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The development of excellent full-spectrum photocatalysts is of vital significance to its practical application in environmental remediation. Herein, flower-like Ag2CO3/BiOCOOH type I heterostructures were prepared via a facile method and exhibited powerful photocatalytic activity by removing various toxic pollutants (rhodamine B, methyl blue, and tetracycline hydrochloride) under simulated sunlight irradiation. The boosted photocatalytic performance is attributed to the expanded range of the absorption spectrum and alleviated separation rate of the photo-induced electrons and holes. The photoluminescence spectra and trapping experiment were applied to clarify the photocatalytic reaction mechanism of Ag2CO3/BiOCOOH. The holes and â¢O2- were detected as the dominant reactive species involved in pollutant degradation. This work provides a novel full-spectrum-driven photocatalyst of Ag2CO3/BiOCOOH, which could effectively degrade toxic pollutants under simulated sunlight.
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BACKGROUND: Our pilot study using miRNA PCR array found that miRNA-29b (miR-29b) is differentially expressed in primary cultured CD133-positive A549 cells compared with CD133-negative A549 cells. METHODS: Ten human non-small cell lung cancer (NSCLC) cell lines and samples from thirty patients with NSCLC were analyzed for the expression of miR-29b by quantitative RT-PCR. Bioinformatics analysis combined with tumor metastasis PCR array showed the potential target genes for miR-29b. miR-29b lentivirus and inhibitors were transfected into NSCLC cells to investigate its role on regulating cell proliferation which was measured by CCK-8 assay in vitro and nude mice xenograft tumor assay in vivo. Cell motility ability was evaluated by transwell assay. The target genes of miR-29b were determined by luciferase assay, quantitative RT-PCR and western blot. RESULTS: Bioinformatics analysis combined with tumor metastasis PCR array showed that matrix metalloproteinase 2 (MMP2) and PTEN could be important target genes of miR-29b. The expression of miR-29b was down regulated in NSCLC tissues compared to the normal tissues. Clinicopathological analysis demonstrated that miR-29b had significant negative correlation with lymphatic metastasis. The gain-of-function studies revealed that ectopic expression of miR-29b decreased cell proliferation, migration and invasion abilities of NSCLC cells. In contrasts, loss-of-function studies showed that inhibition of miR-29b promoted cell proliferation, migration and invasion of NSCLC cells in vitro. Nude mice xenograft tumor assay confirmed that miR-29b inhibited lung cancer growth in vivo. High-invasion (A549-H) and low-invasion (A549-L) NSCLC cell sublines from A549 cells were created by using the repeated transwell assay aimed to confirm the effect of miR-29b on migration and invasion of NSCLC. Furthermore, the dual-luciferase reporter assay demonstrated that miR-29b inhibited the expression of the luciferase gene containing the 3'-UTRs of MMP2 and PTEN mRNA. Western blotting and quantitative RT-PCR indicated that miR-29b down-regulated the expression of MMP2 at the protein and mRNA levels. CONCLUSION: Taken together, our results demonstrate that miR-29b serves as a tumor metastasis suppressor, which suppresses NSCLC cell metastasis by directly inhibiting MMP2 expression. The results show that miR-29b may be a novel therapeutic candidate target to slow NSCLC metastasis.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Metaloproteinasa 2 de la Matriz/genética , MicroARNs/biosíntesis , Fosfohidrolasa PTEN/genética , Animales , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular/fisiología , Xenoinjertos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , MicroARNs/genética , Persona de Mediana Edad , Metástasis de la Neoplasia , Fosfohidrolasa PTEN/metabolismo , Proyectos Piloto , TransfecciónRESUMEN
MicroRNAs play key roles in tumour metastasis. miR29b was previously reported to act as a tumour suppressor or an oncogene in diverse cancers. However, its accurate function and mechanism in metastasis of no-small cell lung cancer (NSCLC) are not well known. In this study, we describe the function of miR29b in NSCLC metastasis and its regulatory mechanisms. We found that miR29b is downregulated in high-metastatic NSCLC cells and low-expression of miR29b in primary NSCLC tissue was correlated with lymph node metastasis. Both gain- and loss-of-function study indicated overexpression of miR29b could suppress migration and invasion abilities of high-metastatic NSCLC cells, while downregulation of miR29b expression promoted migration and invasion of low-metastatic NSCLC cells in vitro. Moreover, introduction of miR29b inhibited highmetastatic NSCLC cells, in vivo, metastasis to liver and lungs. Mechanistically, miR29b, induced by the transcription factor SRF, posttranscriptionally downregulates MMP2 expression by directly targeting its 3'-untranslated regions. These findings indicate a new regulatory mode, whereby miR29b, which is inhibited by its upstream transcription factor SRF, was able to promote its direct target MMP2 leading to NSCLC invasion and metastasis.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Metaloproteinasa 2 de la Matriz/genética , MicroARNs/genética , Factor de Respuesta Sérica/genética , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , MicroARNs/metabolismo , Invasividad Neoplásica , Metástasis de la Neoplasia , Trasplante de Neoplasias , Factor de Respuesta Sérica/metabolismoRESUMEN
MicroRNAs have been implicated in various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma; however, the expression of microRNAs and their role in Merkel cell carcinoma (MCC) have yet to be explored in depth. To identify microRNAs specific to MCC (MCC-miRs), next-generation sequencing (NGS) of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin. Comparison of the profiles identified several microRNAs upregulated and downregulated in MCC. For validation, their expression was measured via qRT-PCR in a larger group of MCC and in a comparison group of non-MCC cutaneous tumors and normal skin. Eight microRNAs were upregulated in MCC: miR-502-3p, miR-9, miR-7, miR-340, miR-182, miR-190b, miR-873, and miR-183. Three microRNAs were downregulated: miR-3170, miR-125b, and miR-374c. Many of these MCC-miRs, the miR-183/182/96a cistron in particular, have connections to tumorigenic pathways implicated in MCC pathogenesis. In situ hybridization confirmed that the highly expressed MCC-miR, miR-182, is localized within tumor cells. Furthermore, NGS and qRT-PCR reveal that several of these MCC-miRs are highly expressed in the patient-derived MCC cell line, MS-1. These data indicate that we have identified a set of MCC-miRs with important implications for MCC research.
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OBJECTIVE: To study the effect of the synthetic peptide RGDSY-CTTHWGFTLC on the biological behavior of breast cancer MCF-7 cells in vitro. METHODS: MCF-7 cells were incubated with different concentrations of the synthesized peptide RGDSY-CTTHWGFTLC (RGDSY-CTT), the positive control peptide CTTHWGFTLC (CTT), or the negative control peptide STTHWGFTLS (STT) in fibronectin-coated 96-well plates for different time lengths, and the changes in cell adhesion, invasiveness, proliferation, apoptosis and cell cycle were detected using Transwell chamber assay, MTT assay, and flow cytometry. RESULTS: Incubation of the cells with 50, 100 and 200 µg/ml of RGDSY-CTT caused a significant concentration- dependent inhibition of the cell adhesion (cell adhesion rates of 85.1%, 74.1% and 63.8%, respectively) with stronger effects than CTT (P<0.05). At 100 and 200 µg/ml, RGDSY-CTT significantly inhibited the invasion (with inhibition rate of 41.8% and 63.9%, respectively) of MCF-7 cells with an effect similar to that by CTT (P>0.05). At 50, 100 and 200 µg/ml, RGDSY-CTT concentration-dependently suppressed MCF-7 cell proliferation (with cell proliferation rates of 98.8%, 82.4% and 63.0%, respectively), and this inhibitory effect was stronger than that of CTT at 100 and 200 µg/ml (P<0.05). The results of flow cytometry also demonstrated a stronger apoptosis-inducing effect of RGDSY-CTT (76.7%) than that in CTT, STT and the blank control groups (P<0.05). CONCLUSIONS: RGDSY-CTT can inhibit cell invasion, suppress adhesion and proliferation, and induce apoptosis in MCF-7 cells.