RESUMO
The construction of the unsymmetrical 1,2-bis(silylene) pentacarbonyl chromium(0) complex 1 was achieved through the reaction of chlorosilylene with half an equivalent of K2Cr(CO)5. X-ray diffraction analysis of 1 confirms the formation of the Si-Si bond and the coordination of one of the silicon atoms to the Cr center. Density functional theory (DFT) calculations disclose that highest occupied molecular orbital (HOMO) mainly corresponds to the lone pair of electrons on the silicon atom and the σ-bonding interaction between two Si atoms. Based on its unique electronic structure, its diverse reactivity toward the transition metal compounds and small molecules was investigated in detail. The reactions of 1 with Fe2(CO)9 or CuCl yielded the 1,2-bis(silylene)-stabilized heterobimetallic complex 2 or oxidized product 3, respectively. Additionally, treatments of 1 with selenium, CO2, or Me3SiN3 led to the formation of the corresponding selenium-, oxo-, and nitrogen-bridged complexes 4-7. All compounds were characterized by multinuclear NMR spectroscopy and X-ray crystallography.
RESUMO
This study aimed to investigate changes in menstruation and the association of the severity of Omicron with menstruation after the nationwide outbreak of COVID-19 in China. A cross-sectional study adopted an electronic questionnaire to conduct an anonymous online survey. The survey targeted women of reproductive age who had been infected with SARS-CoV-2, and were menstruating regularly in the six months prior to the infection, and experienced at least one menstrual cycle after the infection. The 737 included participants were divided into mild and severe groups based on the severity of the infection. Deviations in first menstrual cycle post-infection were reported in 46.4% of participants (mild group 40.1% vs. severe group 55.2%, P<0.05). Menstrual changes were predominantly a late menstrual period (mild group 25.3% vs. severe group 30.4%), a shorter duration of menstrual flow (mild group 10.4% vs. severe group 14.7%), and a decrease in menstrual flow volume (mild group 16% vs. severe group 21.6%). Premenstrual syndrome symptoms in a small number of women were worse compared with pre-infection, especially in the severe group. During the second menstrual period after infection, most participants reported their menstrual characteristics had returned to those of pre-infection (mild group 88% vs. severe group 80.2%, P<0.05). In this investigation, SARS-CoV-2 infection had a substantial effect on women's menstrual characteristics, and the changes were mostly transient. Women with more severe COVID-19 symptoms experienced more significant changes. The potential long-term effects of SARS-CoV-2 on female reproductive health require further observation and research.
Cette étude visait à étudier les changements dans la menstruation et l'association entre la gravité d'Omicron et la menstruation après l'épidémie nationale de COVID-19 en Chine. Une étude transversale a adopté un questionnaire électronique pour mener une enquête anonyme en ligne. L'enquête visait les femmes en âge de procréer qui avaient été infectées par le SRAS-CoV-2, qui avaient leurs règles régulièrement au cours des six mois précédant l'infection et qui ont connu au moins un cycle menstruel après l'infection. Les 737 participants inclus ont été divisés en groupes légers et sévères en fonction de la gravité de l'infection. Des écarts dans le premier cycle menstruel post-infection ont été signalés chez 46,4 % des participantes (groupe léger 40,1 % contre groupe sévère 55,2 %, P <0,05). Les changements menstruels étaient principalement une période menstruelle tardive (groupe léger 25,3 % contre groupe sévère 30,4 %), une durée plus courte du flux menstruel (groupe léger 10,4 % contre groupe sévère 14,7 %) et une diminution du volume du flux menstruel (groupe léger). 16 % contre groupe sévère 21,6 %). Les symptômes du syndrome prémenstruel chez un petit nombre de femmes étaient pires que ceux observés avant l'infection, en particulier dans le groupe sévère. Au cours de la deuxième période menstruelle après l'infection, la plupart des participantes ont déclaré que leurs caractéristiques menstruelles étaient revenues à celles d'avant l'infection (groupe léger 88 % contre groupe sévère 80,2 %, P <0,05). Dans cette enquête, l'infection par le SRAS-CoV-2 a eu un effet substantiel sur les caractéristiques menstruelles des femmes, et les changements ont été pour la plupart transitoires. Les femmes présentant des symptômes plus graves de la COVID-19 ont connu des changements plus importants. Les effets potentiels à long terme du SRAS-CoV-2 sur la santé reproductive des femmes nécessitent des observations et des recherches plus approfondies.
Assuntos
COVID-19 , Síndrome Pré-Menstrual , SARS-CoV-2 , Humanos , Feminino , Estudos Transversais , China/epidemiologia , Adulto , Síndrome Pré-Menstrual/epidemiologia , COVID-19/epidemiologia , Adulto Jovem , Índice de Gravidade de Doença , MenstruaçãoRESUMO
Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer (GC) distinguished by the presence of the EBV genome and limited viral gene expression within malignant epithelial cells. EBV infection is generally thought to be a relatively late event following atrophic gastritis in carcinogenesis, which implies the heterogeneity of EBVaGC. To facilitate the study of the role of EBV in EBVaGC, we established two EBV-positive GC cell lines (AGS-EBV and HGC27-EBV) with an epitheliotropic EBV strain M81 and characterized viral and cellular gene expression profiles in comparison to SNU719, a naturally derived EBV-positive GC cell line. Like SNU719, AGS-EBV and HGC27-EBV stably maintained their EBV genomes and expressed EBV-encoded small RNAs and nuclear antigen EBNA1. Comprehensive analysis of the expression of EBV-encoded miRNAs within the BamHI-A region rightward transcript region, and the transcripts of EBV latent and lytic genes in cell lines, as well as xenografts, reveals that AGS-EBV and HGC27-EBV cells undergo distinct viral expression profiles. A very small fraction of AGS-EBV and SNU719 cells can spontaneously produce infectious progeny virions, while HGC27-EBV does not. AGS-EBV (both M81 and Akata) cells largely mimic SNU719 cells in viral gene expression profiles, and altered cellular functions and pathways perturbed by EBV infection. Phylogenetic analysis of the EBV genome shows both M81 and Akata EBV strains are closely related to clinical EBVaGC isolates. Taken together, these two newly established EBV-positive GC cell lines can serve as models to further investigate the role of EBV in different contexts of gastric carcinogenesis and identify novel therapeutics against EBVaGC.
Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Carcinogênese , Linhagem Celular/metabolismo , Linhagem Celular/virologia , Herpesvirus Humano 4/genética , Filogenia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/virologiaRESUMO
Pre-mRNA splicing is an important step in the posttranscriptional processing of transcripts and a key regulator of development. The heterotrimeric retention and splicing (RES) complex plays vital roles in the growth and development of yeast, zebrafish, and humans by mediating pre-mRNA splicing of multiple genes. However, whether the RES complex is conserved in plants and what specific functions it has remain unknown. In this study, we identified Arabidopsis (Arabidopsis thaliana) BUD13 (AtBUD13), GROWTH, DEVELOPMENT AND SPLICING 1 (GDS1), and DAWDLE (DDL) as the counterparts of the yeast RES complex subunits Bud site selection protein 13 (Bud13), U2 snRNP component Snu17 (Snu17), and Pre-mRNA leakage protein 1, respectively. Moreover, we showed that RES is an ancient complex evolutionarily conserved in eukaryotes. GDS1 directly interacts with both AtBUD13 and DDL in nuclear speckles. The BUD13 domain of AtBUD13 and the RNA recognition motif domain of GDS1 are necessary and sufficient for AtBUD13-GDS1 interaction. Mutants of AtBUD13, GDS1, and DDL failed to properly splice multiple genes involved in cell proliferation and showed defects in early embryogenesis and root development. In addition, we found that GDS1 and DDL interact, respectively, with the U2 small nuclear ribonucleoproteins auxiliary factor AtU2AF65B and the NineTeen Complex-related splicing factor SKIP, which are essential for early steps of spliceosome assembly and recognition of splice sites. Altogether, our work reveals that the Arabidopsis RES complex is important for root and early embryo development by modulating pre-mRNA splicing.
Assuntos
Arabidopsis , Animais , Arabidopsis/metabolismo , Desenvolvimento Embrionário , Humanos , Precursores de RNA/genética , Precursores de RNA/metabolismo , Splicing de RNA/genética , Ribonucleoproteína Nuclear Pequena U2/genética , Ribonucleoproteína Nuclear Pequena U2/metabolismo , Saccharomyces cerevisiae/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
In recent years, major economies have implemented carbon reduction and carbon neutrality policies. Furthermore, with advancements in science and technology, carbon dioxide (CO2) is now considered a valuable raw material for producing carbon-based fuels through hydrogenation. Various concentrations of yttrium (referred to as Y hereafter) were introduced to assess their influence on the catalytic performance of CO2 methanation. At a temperature of 300 °C, the catalyst exhibited an impressive CO2 conversion rate of 78.4% and maintained remarkable stability throughout a rigorous 100 h stability assessment. The findings suggest that the inclusion of yttrium (Y) promotes the formation of oxygen vacancies and alkaline sites on the catalyst. This, in turn, enhances the reducibility of nickel species, improves the dispersion of nickel particles, and plays a pivotal role in enhancing thermal stability. Furthermore, it offers an innovative design approach for creating highly efficient composite CO2 methanation catalysts by controlling particle size and harnessing synergistic catalytic effects at the metal/support interface.
RESUMO
Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are one of the most prescribed antihypertensive medications. Previous studies showed RAAS inhibitors increase the expression of ACE2, a cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which provokes a concern that the use of ACEI and ARB in hypertensive individuals might lead to increased mortality and severity of coronavirus disease 2019 (COVID-19). To further investigate the effects of ACEI/ARB on COVID-19 patients, we systematically reviewed relevant studies that met predetermined inclusion criteria in search of PubMed, Embase, Cochrane Library databases, medRxiv, and bioRxiv. The search strategy included clinical data published through October 12, 2020. Twenty-six studies involving 8104 hypertensive patients in ACEI/ARB-treated group and 8203 hypertensive patients in non-ACEI/ARB-treated group were analyzed. Random-effects meta-analysis showed ACEI/ARB treatment was significantly associated with a lower risk of mortality in hypertensive COVID-19 patients (odds ratio [OR] = 0.624, 95% confidence interval [CI] = 0.457-0.852, p = .003, I2 = 74.3%). Meta-regression analysis showed that age, gender, study site, Newcastle-Ottawa Scale scores, comorbidities of diabetes, coronary artery disease, chronic kidney disease, or cancer has no significant modulating effect of ACEI/ARB treatment on the mortality of hypertensive COVID-19 patients (all p > .1). In addition, the ACEI/ARB treatment was associated with a lower risk of ventilatory support (OR = 0.682, 95% CI = 0.475-1.978, p = .037, I2 = 0.0%). In conclusion, these results suggest that ACEI/ARB medications should not be discontinued for hypertensive patients in the context of COVID-19 pandemic.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , COVID-19/complicações , COVID-19/mortalidade , Hipertensão/tratamento farmacológico , Comorbidade , Feminino , Humanos , Hipertensão/complicações , Masculino , Prognóstico , Fatores de RiscoRESUMO
Pre-mRNA splicing is an important step for gene expression regulation. Yeast Bud13p (bud-site selection protein 13) regulates the budding pattern and pre-mRNA splicing in yeast cells; however, no Bud13p homologs have been identified in plants. Here, we isolated two mutants that carry T-DNA insertions at the At1g31870 locus and shows early embryo lethality and seed abortion. At1g31870 encodes an Arabidopsis homolog of yeast Bud13p, AtBUD13. Although AtBUD13 homologs are widely distributed in eukaryotic organisms, phylogenetic analysis revealed that their protein domain organization is more complex in multicellular species. AtBUD13 is expressed throughout plant development including embryogenesis and AtBUD13 proteins is localized in the nucleus in Arabidopsis. RNA-seq analysis revealed that AtBUD13 mutation predominantly results in the intron retention, especially for shorter introns (≤100 bases). Within this group of genes, we identified 52 genes involved in embryogenesis, out of which 22 are involved in nucleic acid metabolism. Our results demonstrate that AtBUD13 plays critical roles in early embryo development by effecting pre-mRNA splicing.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Desenvolvimento Embrionário/fisiologia , Proteínas Nucleares/metabolismo , Fatores de Processamento de RNA/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/classificação , Proteínas de Arabidopsis/genética , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica de Plantas/genética , Genes de Plantas/genética , Íntrons , Mutação , Proteínas Nucleares/classificação , Proteínas Nucleares/genética , Filogenia , Plantas Geneticamente Modificadas , Domínios Proteicos , Precursores de RNA/genética , Splicing de RNA , Fatores de Processamento de RNA/classificação , Fatores de Processamento de RNA/genética , Alinhamento de Sequência , Análise de SequênciaRESUMO
By 27 February 2020, the outbreak of coronavirus disease 2019 (COVID-19) caused 82 623 confirmed cases and 2858 deaths globally, more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and Middle East respiratory syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013, respectively. COVID-19 has spread to 46 countries internationally. Total fatality rate of COVID-19 is estimated at 3.46% by far based on published data from the Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID-19 is around 6.4 days, ranges from 0 to 24 days. The basic reproductive number (R0 ) of COVID-19 ranges from 2 to 3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID-19. Nosocomial transmission was another severe problem. A total of 3019 health workers were infected by 12 February 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID-19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID-19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID-19 and enhance our control measures in the future.
Assuntos
Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , COVID-19 , Vacinas contra COVID-19 , China/epidemiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Humanos , Imunização Passiva/métodos , Linfopenia/fisiopatologia , Linfopenia/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Prevalência , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/transmissão , Análise de Sobrevida , Trombocitopenia/fisiopatologia , Trombocitopenia/virologia , Vacinas Virais/biossíntese , Soroterapia para COVID-19RESUMO
Flowering transition is regulated by complex genetic networks in response to endogenous and environmental signals. Pre-mRNA splicing is an essential step for the post-transcriptional regulation of gene expression. Alternative splicing of key flowering genes has been investigated in detail over the past decade. However, few splicing factors have been identified as being involved in flowering transition. Human heterodimeric splicing factor U2 snRNP auxiliary factor (U2AF) consists of two subunits, U2AF35 and U2AF65, and functions in 3' splice site recognition in mRNA splicing. Recent studies reveal that Arabidopsis U2AF65a/b and U2AF35a/b play important roles in the splicing of key flowering genes. We summarize recent advances in research on splicing-regulated flowering transition by focusing on the role of Arabidopsis U2AF in the splicing of key flowering-related genes at ambient temperature and in the abscisic acid signaling pathways.
Assuntos
Processamento Alternativo , Proteínas de Arabidopsis/metabolismo , Flores/fisiologia , Proteínas de Domínio MADS/metabolismo , Ribonucleoproteína Nuclear Pequena U2/fisiologia , Ácido Abscísico/metabolismo , ArabidopsisRESUMO
Unfortunately, the name of the corresponding author (Wenxiang Wu) was missing in the author group section of the published paper.
RESUMO
Ground deformation (GD) has been widely reported as a global issue and is now an ongoing problem that will profoundly endanger the public safety. GD is a complex and dynamic problem with many contributing factors that occur over time. In the literature, there are only a few methods that can effectively monitor GD. Microwave remote sensing data such as interferometric synthetic aperture radar (InSAR) are mostly adopted to assess GD. These data can reveal the surface deforming areas with great precision, mapping GD results at a large scale. In this study, the effects of GD and the influencing factors, such as the building area, the water level, the cumulative precipitation, and the cumulative temperature, are modeled in the Erhai region with small baseline subset interferometric SAR (SBAS-InSAR) data that are applied using machine learning (ML) methods. The ML methods, namely, multiple linear regression (MLR), multilayer perceptron backpropagation (MLP-BP), least squares support vector machine (LSSVM), and particle swarm optimization (PSO)-LSSVM, are used to predict GD, and the results are compared. Particularly, the PSO-LSSVM method has obtained the least root mean square error (RMSE) and mean relative error (MRE) of 11.448 and 0.112, respectively. Therefore, the results have proven that the proposed PSO-LSSVM is very efficient in analyzing GD.
Assuntos
Monitoramento Ambiental , Aprendizado de Máquina , China , Redes Neurais de Computação , Máquina de Vetores de SuporteRESUMO
In mammalians and yeast, the splicing factor U2AF65/Mud2p functions in precursor messenger RNA (pre-mRNA) processing. Arabidopsis AtU2AF65b encodes a putative U2AF65 but its specific functions in plants are unknown. This paper examines the function of AtU2AF65b as a negative regulator of flowering time in Arabidopsis. We investigated the expression and function of AtU2AF65b in abscisic acid (ABA)-regulated flowering as well as the transcript abundance and pre-mRNA splicing of flowering-related genes in the knock-out mutants of AtU2AF65b. The atu2af65b mutants show early-flowering phenotype under both long-day and short-day conditions. The transcript accumulation of the flowering repressor gene FLOWERING LOCUS C (FLC) is reduced in the shoot apex of atu2af65b, due to both increased intron retention and reduced transcription activation. Reduced transcription of FLC results, at least partially, from the abnormal splicing and reduced transcript abundance of ABSCISIC ACID-INSENSITIVE 5 (ABI5), which encodes an activator of FLC in ABA-regulated flowering signaling. Additionally, the expression of AtU2AF65b is promoted by ABA. Transition to flowering and splicing of FLC and ABI5 in the atu2af65b mutants are compromised during ABA-induced flowering. ABA-responsive AtU2AF65b functions in the pre-mRNA splicing of FLC and ABI5 in shoot apex, whereby AtU2AF65b is involved in ABA-mediated flowering transition in Arabidopsis.
Assuntos
Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Flores/fisiologia , Proteínas de Domínio MADS/genética , Splicing de RNA/genética , Proteínas de Arabidopsis/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Núcleo Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Íntrons/genética , Proteínas de Domínio MADS/metabolismo , Mutação/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Plântula/metabolismo , Fator de Processamento U2AF/metabolismo , Transcrição Gênica , Regulação para Cima/genéticaRESUMO
A quantum network consists of independent sources distributing entangled states to distant nodes which can then perform entangled measurements, thus establishing correlations across the entire network. But how strong can these correlations be? Here we address this question, by deriving bounds on possible quantum correlations in a given network. These bounds are nonlinear inequalities that depend only on the topology of the network. We discuss in detail the notably challenging case of the triangle network. Moreover, we conjecture that our bounds hold in general no-signaling theories. In particular, we prove that our inequalities for the triangle network hold when the sources are arbitrary no-signaling boxes which can be wired together. Finally, we discuss an application of our results for the device-independent characterization of the topology of a quantum network.
RESUMO
Metformin is a promising drug for cancer prevention and treatment, especially in the diabetic population. We aimed to test whether 14-3-3zeta affects the anticancer effect of metformin on colorectal carcinoma (CRC). In this study, we confirmed that higher 14-3-3zeta expression was found in CRC tissues than in pericarcinoma tissues, and in CRC tissue of patients with diabetes than in those without diabetes. A knockdown of 14-3-3zeta inhibited CRC proliferation and promoted apoptosis in vitro and in vivo. Then, we created stable cell lines with under-expressed 14-3-3zeta from SW480 and HCT15 cells after infection by a lentiviral vector carrying short hairpin RNA targeting 14-3-3zeta (named LV-sh14-3-3zeta). Of note, metformin induced apoptosis and retarded tumor growth in the CRCs with overexpressed 14-3-3zeta, whereas this action was attenuated when 14-3-3zeta was knocked down. Moreover, either metformin or downregulation of 14-3-3zeta noticeably activated AMP-dependent protein kinase (AMPK) signaling, whereas the effect of metformin was attenuated when the 14-3-3zeta expression was decreased. Taken together, our results suggest that 14-3-3zeta may be associated with carcinogenesis and poor prognosis of CRCs associated with diabetes, and metformin may reverse the AMPK inhibition caused by 14-3-3zeta in CRCs in the background of diabetes. Our study should lead to a better understanding of the anticancer activity of metformin and points to possible application of metformin to the treatment of cancers overexpressing 14-3-3zeta.
Assuntos
Proteínas 14-3-3/metabolismo , Antineoplásicos/farmacologia , Neoplasias Colorretais/patologia , Complicações do Diabetes/metabolismo , Metformina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/complicações , Neoplasias Colorretais/metabolismo , Diabetes Mellitus/metabolismo , Feminino , Humanos , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVES: To analyze the influence of bone morphogenetic proteins (BMPs) from CT26 on PD-L1 of dendritic cells and macrophages. METHODS: In vivo, we respectively inoculated CT26 colon cancer cells subcutaneously and intraperitoneally to BALB/c mice.The mice were randomly assigned to three groups and treated with normal saline; BMPs inhibitor LDN193189; BMPs inhibitor LDN193189 combined with paclitaxel, respectively. The treatments started on the eighth day after inoculating, when the tumor volume reached 150 mm3 or the abdominal circumference was greater than 6 cm. After 2 weeks of treatments, the mice were sacrificed.The counts of dendritic cells and macrophages and the expression of PD-L1 in tumors or ascites were detected by flow cytometry (FCM).In vivo, the dendritic cells and macrophages from normal BALB/c mice bone marrow were exposed to: no treatment; CT26 supernatant; CT26; CT26 supernatant and LDN193189; CT26 and LDN193189; CT26 supernatant, LDN193189 and paclitaxel; CT26, LDN193189 and paclitaxel. BMPs from CT26 was detected by ELISA.The counts of dendritic cells and macrophages and their PD-L1 expressions were detected by FCM. IRF-1 expression was detected by real-time (RT)-PCR and Western blot. RESULTS: In vivo, LDN193189 treated mice had the greatest tumor size or abdominal circumference, with least dendritic cells andCM(155.3mm]macrophages and expressions of PD-L1.In vivo, ELISA test results showed that the concentration of BMPs in CT26 supernatant was (0.59±0.09) ng/mL. FCM, RT-PCR and Western blot showed that dendritic cells and macrophages exposed to CT26 supernatant and LDN193189 or CT26 and LDN193189 expressed the least PD-L1 and IRF-1, which was close to those without treatment. While added the PTX to the above treatment, the expressions of PD-L1 and IRF-1 increased in the test results. CONCLUSIONS: BMPs from CT26 up-regulate the expression of PD-L1 in murine dendritic cells and macrophages.
Assuntos
Antígeno B7-H1/metabolismo , Proteínas Morfogenéticas Ósseas/farmacologia , Células Dendríticas/metabolismo , Macrófagos/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Linhagem Celular Tumoral , Neoplasias do Colo , Meios de Cultivo Condicionados/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologiaRESUMO
BACKGROUND: Acne is a chronic skin disease characterised by inflamed spots and blackheads on the face, neck, back, and chest. Cysts and scarring can also occur, especially in more severe disease. People with acne often turn to complementary and alternative medicine (CAM), such as herbal medicine, acupuncture, and dietary modifications, because of their concerns about the adverse effects of conventional medicines. However, evidence for CAM therapies has not been systematically assessed. OBJECTIVES: To assess the effects and safety of any complementary therapies in people with acne vulgaris. SEARCH METHODS: We searched the following databases from inception up to 22 January 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2014,Issue 1), MEDLINE (from 1946), Embase (from 1974), PsycINFO (from 1806), AMED (from 1985), CINAHL (from 1981), Scopus (from 1966), and a number of other databases listed in the Methods section of the review. The Cochrane CAM Field Specialised Register was searched up to May 2014. We also searched five trials registers and checked the reference lists of articles for further references to relevant trials. SELECTION CRITERIA: We included parallel-group randomised controlled trials (or the first phase data of randomised cross-over trials) of any kind of CAM, compared with no treatment, placebo, or other active therapies, in people with a diagnosis of acne vulgaris. DATA COLLECTION AND ANALYSIS: Three authors collected data from each included trial and evaluated the methodological quality independently. They resolved disagreements by discussion and, as needed, arbitration by another author. MAIN RESULTS: We included 35 studies, with a total of 3227 participants. We evaluated the majority as having unclear risk of selection, attrition, reporting, detection, and other biases. Because of the clinical heterogeneity between trials and the incomplete data reporting, we could only include four trials in two meta-analyses, with two trials in each meta-analysis. The categories of CAM included herbal medicine, acupuncture, cupping therapy, diet, purified bee venom (PBV), and tea tree oil. A pharmaceutical company funded one trial; the other trials did not report their funding sources.Our main primary outcome was 'Improvement of clinical signs assessed through skin lesion counts', which we have reported as 'Change in inflammatory and non-inflammatory lesion counts', 'Change of total skin lesion counts', 'Skin lesion scores', and 'Change of acne severity score'. For 'Change in inflammatory and non-inflammatory lesion counts', we combined 2 studies that compared a low- with a high-glycaemic-load diet (LGLD, HGLD) at 12 weeks and found no clear evidence of a difference between the groups in change in non-inflammatory lesion counts (mean difference (MD) -3.89, 95% confidence interval (CI) -10.07 to 2.29, P = 0.10, 75 participants, 2 trials, low quality of evidence). However, although data from 1 of these 2 trials showed benefit of LGLD for reducing inflammatory lesions (MD -7.60, 95% CI -13.52 to -1.68, 43 participants, 1 trial) and total skin lesion counts (MD -8.10, 95% CI -14.89 to -1.31, 43 participants, 1 trial) for people with acne vulgaris, data regarding inflammatory and total lesion counts from the other study were incomplete and unusable in synthesis.Data from a single trial showed potential benefit of tea tree oil compared with placebo in improving total skin lesion counts (MD -7.53, 95% CI -10.40 to -4.66, 60 participants, 1 trial, low quality of evidence) and acne severity scores (MD -5.75, 95% CI -9.51 to -1.99, 60 participants, 1 trial). Another trial showed pollen bee venom to be better than control in reducing numbers of skin lesions (MD -1.17, 95% CI -2.06 to -0.28, 12 participants, 1 trial).Results from the other 31 trials showed inconsistent effects in terms of whether acupuncture, herbal medicine, or wet-cupping therapy were superior to controls in increasing remission or reducing skin lesions.Twenty-six of the 35 included studies reported adverse effects; they did not report any severe adverse events, but specific included trials reported mild adverse effects from herbal medicines, wet-cupping therapy, and tea tree oil gel.Thirty trials measured two of our secondary outcomes, which we combined and expressed as 'Number of participants with remission'. We were able to combine 2 studies (low quality of evidence), which compared Ziyin Qinggan Xiaocuo Granule and the antibiotic, minocycline (100 mg daily) (worst case = risk ratio (RR) 0.49, 95% CI 0.09 to 2.53, 2 trials, 206 participants at 4 weeks; best case = RR 2.82, 95% CI 0.82 to 9.06, 2 trials, 206 participants at 4 weeks), but there was no clear evidence of a difference between the groups.None of the included studies assessed 'Psychosocial function'.Two studies assessed 'Quality of life', and significant differences in favour of the complementary therapy were found in both of them on 'feelings of self-worth' (MD 1.51, 95% CI 0.88 to 2.14, P < 0.00001, 1 trial, 70 participants; MD 1.26, 95% CI 0.20 to 2.32, 1 trial, 46 participants) and emotional functionality (MD 2.20, 95% CI 1.75 to 2.65, P < 0.00001, 1 trial, 70 participants; MD 0.93, 95% CI 0.17 to 1.69, 1 trial, 46 participants).Because of limitations and concerns about the quality of the included studies, we could not draw a robust conclusion for consistency, size, and direction of outcome effects in this review. AUTHORS' CONCLUSIONS: There is some low-quality evidence from single trials that LGLD, tea tree oil, and bee venom may reduce total skin lesions in acne vulgaris, but there is a lack of evidence from the current review to support the use of other CAMs, such as herbal medicine, acupuncture, or wet-cupping therapy, for the treatment of this condition. There is a potential for adverse effects from herbal medicines; however, future studies need to assess the safety of all of these CAM therapies. Methodological and reporting quality limitations in the included studies weakened any evidence. Future studies should be designed to ensure low risk of bias and meet current reporting standards for clinical trials.
Assuntos
Acne Vulgar/terapia , Terapias Complementares , Acne Vulgar/patologia , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Venenos de Abelha/uso terapêutico , Terapias Complementares/efeitos adversos , Humanos , Preparações de Plantas/uso terapêutico , Qualidade de Vida , Viés de Seleção , Óleo de Melaleuca/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Guizhi Fuling Formula is widely applied for uterine fibroids in China. Many clinical trials are reported. This study assessed the efficacy and safety of Guizhi Fuling Formula for the treatment of uterine fibroids. METHODS: PubMed, Cochrane CENTRAL, EMBASE, and four Chinese databases were searched through May 2013. We included randomised controlled trials (RCTs) that tested Guizhi Fuling Formula for uterine fibroids, compared with no intervention, placebo, pharmaceutical medication, or other Chinese patent medicines approved by the State Food and Drug Administration of China. Authors extracted data and assessed the quality independently. We applied RevMan 5.2.0 software to analyse data of included randomised trials. RESULTS: A total of 38 RCTs involving 3816 participants were identified. The methodological quality of the included trials was generally poor. Meta-analyses demonstrated that Guizhi Fuling Formula plus mifepristone were more effective than mifepristone alone in reducing the volume of fibroids (in total volume of multiple fibroids, MD -19.41 cm(3), 95% CI -28.68 to -10.14; in average volume of multiple fibroids, MD -1.00 cm(3), 95% CI -1.23 to -0.76; in average volume of maximum fibroids, MD -3.35 cm(3), 95% CI -4.84 to -1.87, I(2) = 93%, random effects model). Guizhi Fuling Formula significantly improved symptoms of dysmenorrhea either when it was used alone (RR 2.27, 95% CI 1.04 to 4.97) or in combination with mifepristone (RR 2.35, 95% CI 1.15 to 4.82). No serious adverse events were reported. CONCLUSIONS: Guizhi Fuling Formula appears to have additional benefit based on mifepristone treatment in reducing volume of fibroids. However, due to high risk of bias of the trials, we could not draw confirmative conclusions on its benefit. Future clinical trials should be well-designed and avoid the issues that are identified in this study.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Leiomioma/tratamento farmacológico , Fitoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Viés , China , Terapias Complementares/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Dismenorreia/tratamento farmacológico , Feminino , Humanos , Leiomioma/patologia , Mifepristona/uso terapêutico , Fitoterapia/efeitos adversosRESUMO
Clinical trial protocol is the document that illustrates the background of a clinical trial, theoretic basis, objective, design, methods, and organization, as well as statistical calculating, implement, and conditions for completion. Clinical trial protocol is the basic measure for ensuring the validity of scientific results and reducing bias. In order to optimize the design of clinical trial protocol, we generalize main problems in Chinese medicine clinical trials, key points of clinical trial protocol, as well as report standards.
Assuntos
Ensaios Clínicos como Assunto , Medicina Tradicional Chinesa , Projetos de Pesquisa , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Projetos de Pesquisa/normasRESUMO
Purpose: This article aims to present a case report of a patient with Follicular occlusion triad (FOT) who achieved successful disease control with adalimumab combined with isotretinoin and provide a comprehensive review of the current research progress on biologic therapies for FOT.Methods: We report a case of a 22-year-old female patient diagnosed with FOT, who was treated with adalimumab combined with isotretinoin after failing to respond to conventional therapies. A systematic literature review was conducted to summarize the current research progress on biologic therapies for FOT, including TNF-α inhibitors, IL-17 inhibitors, IL-12/IL-23 inhibitors, IL-23 inhibitors, IL-1 inhibitors, and other novel biologic agents.Results: The patient achieved significant improvement in skin lesions, pain, and quality of life after three months of treatment with adalimumab combined with isotretinoin, without experiencing severe adverse reactions. The literature review revealed that adalimumab and secukinumab are the two FDA-approved biologics for FOT, while others, such as bimekizumab, infliximab, anakinra, and bermekimab, have shown promise in clinical studies.Conclusions: Biologic therapies have revolutionized FOT management, providing effective options for patients unresponsive to conventional treatments. As our understanding of FOT pathogenesis and the mechanisms of action of biologics grows, further advancements in biologic therapies for FOT are expected.
Assuntos
Adalimumab , Fármacos Dermatológicos , Isotretinoína , Feminino , Humanos , Adulto Jovem , Adalimumab/uso terapêutico , Terapia Biológica , Fármacos Dermatológicos/uso terapêutico , Quimioterapia Combinada , Isotretinoína/uso terapêutico , Resultado do TratamentoRESUMO
Phosphine catalysis generally relies on the potential of carbanion-phosphonium zwitterions that are generated via nucleophilic addition of phosphine catalyst to electrophilic reactants. Consequently, structural modification of zwitterions using distinct electrophilic reactants has emerged as a prominent strategy to enhance catalysis diversity. Herein, we present an alternative strategy that utilizes AgF additive to expand phosphine catalysis. We find that AgF can readily transform the canonical carbanion-phosphonium zwitterion into silver enolate-fluorophosphorane intermediate, eventually furnishing a P(III)/P(V) catalytic cycle. This strategy has been successfully applied to the phosphine-catalyzed reaction of 2-substituted allenoate and imine, resulting in the transition from Kwon [4 + 2] cycloaddition to [3 + 2] cycloaddition. This [3 + 2] cycloaddition features remarkable diastereoselectivity, high yield, and broad substrate scope. Experimental and computational studies have validated the proposed mechanism. Given the prevalence of carbanion-phosphonium zwitterions in phosphine catalysis, this AgF-assisted strategy is believed to hold significant potential for advancing P(III)/P(V) catalysis.