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1.
J Chem Phys ; 160(20)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38775246

RESUMO

Zeolitic Imidazolate Frameworks-8 (ZIF-8) is commonly used as an ideal precursor for non-noble metal catalysts because of its high specific surface area, ultra-high porosity, and N-rich content. Upon pyrolyzing ZIF-8 at 900 °C in Ar, the resulting material, referred to as Z8, displayed good activity toward the oxygen reduction reaction (ORR). Then the ZIF-8 was mixed with various conductive carbon materials, such as multiwall carbon nanotubes (MWCNTs), Acetylene black (ACET), Vulcan XC-72R (XC-72R), and Ketjenblack EC-600JD (EC-600JD), to form Z8 composites. The Z8/MWCNTs composite exhibited enhanced ORR activity owing to its network structure, meso-/microporous hierarchical porous structure, improved electrical conductivity, and graphitization. Subsequently, iron and nitrogen co-doping is achieved through the pyrolysis of a mixture comprising Fe, N precursor, and ZIF-8/MWCNTs, which is denoted as FeN-Z8/MWCNTs. The intrinsically high electrical conductivity of MWCNTs facilitated efficient electron transfer during the ORR, while the meso-/microporous hierarchical porous structure and network structure of Fe, N co-doped ZIF-8/MWCNTs promoted oxygen transport. The presence of Fe-containing species in the catalyst acted as activity centers for ORR. This strategy of preparing Z8 composites and modifying them with Fe, N co-doping offers an insightful approach to designing cost-effective electrocatalysts.

2.
Sci Rep ; 13(1): 15103, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37699925

RESUMO

Obstructive sleep apnea (OSA) is an upper airway disorder occurring during sleep and is associated with atherosclerosis (AS). AS is a cardiovascular disease caused by environmental and genetic factors, with a high global mortality rate. This study investigated common pathways and potential biomarkers of OSA and AS. Microarray data were downloaded from the Gene Expression Omnibus (GEO) database and used to screen for differentially expressed genes (DEGs) in the OSA and AS datasets. A weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression modules of OSA and AS. The least absolute shrinkage and selection operators (LASSO) were used to determine critical biomarkers. Immune cell infiltration analysis was used to investigate the correlation between immune cell infiltration and common biomarkers of OSA and AS. Results revealed that differentially expressed genes may be involved in inflammatory processes, chemokine signaling pathways, and molecular changes in cell adhesion. ERBB receptor feedback inhibitor 1 (ERRFI1) was the best-shared biomarker for OSA and AS. Immune infiltration analysis showed that ERRFI1 expression was correlated with immune cell changes. Changes in immune pathways, inflammatory processes, and cell adhesion molecules may underlie the pathogenesis of both diseases, and ERRFI1 may be a potential diagnostic marker for patients with OSA and AS.


Assuntos
Aterosclerose , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/genética , Sono , Aterosclerose/genética , Biomarcadores , Biologia Computacional , Proteínas Ativadoras de GTPase
3.
Front Immunol ; 14: 1330099, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38259489

RESUMO

Radiotherapy is one important treatment for malignant tumours. It is widely believed today that radiotherapy has not only been used as a local tumour treatment method, but also can induce systemic anti-tumour responses by influencing the tumour microenvironment, but its efficacy is limited by the tumour immunosuppression microenvironment. With the advancement of technology, immunotherapy has entered a golden age of rapid development, gradually occupying a place in clinical tumour treatment. Regulatory T cells (Tregs) widely distributing in the tumour microenvironment play an important role in mediating tumour development. This article analyzes immunotherapy, the interaction between Tregs, tumours and radiotherapy. It briefly introduces immunotherapies targeting Tregs, aiming to provide new strategies for radiotherapy combined with Immunotherapy.


Assuntos
Neoplasias , Linfócitos T Reguladores , Humanos , Imunoterapia , Terapia de Imunossupressão , Tecnologia , Neoplasias/terapia , Microambiente Tumoral
4.
Am J Transl Res ; 14(11): 8263-8270, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505294

RESUMO

OBJECTIVE: Studies have shown that dyslipidemia may contribute to chronic tissue hypoxia. However, it remains unclear whether dyslipidemia affects chronic hypoxia in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Therefore, from a clinical practice perspective, the purpose of this study was to investigate the effect of dyslipidemia on chronic hypoxia in OSAHS patients. METHOD: In athis cross-sectional survey, 320 consecutive OSAHS patients were enrolled. By screening under different conditions, 211 patients were finally enrolled in the study. Patients were grouped according to apnea-hypopnea index (AHI), into a mild-to-moderate (AHI < 30) group and severe OSAHS group (AHI ≥ 30). RESULTS: Comparative analysis shows that 45% of mild-to-moderate OSAHS patients had severe hypoxemia. Univariate and multivariate regression analyses showed that AHI, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) had independent effects on lowest oxygen saturation (LSpO2), and that AHI and TG levels had independent effects on mean oxygen saturation (MSpO2). The patients were stratified by AHI and further grouped by TG and HDL-C abnormalities in each subgroup. A difference analysis showed that LSpO2 and MSpO2 were significantly decreased in OSAHS patients with dyslipidemia (high TG and low HDL-C levels) in the AHI ≥ 30 subgroup (P < 0.05). Finally, in order to further clarify the impact of the selected indicators of hypoxemia in OSAHS patients with different degrees of airway obstruction, subgroup analysis was conducted based on OSAHS severity. In the AHI < 30 subgroup, LSpO2 was significantly decreased in patients with abnormal HDL-C. CONCLUSION: The results of this study indicate that abnormalities in TG and HDL-C, in addition to upper airway obstruction, are among the factors that aggravate chronic hypoxia in tissues from OSAHS patients.

5.
Front Psychol ; 13: 978054, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36337473

RESUMO

Spiritual pedagogy (SP) as a new educational theory aims to apply cultural and spiritual values in classroom practices. It has been the focus of research in different fields such as counselling, management, and science in the past decades. However, its application in second/foreign language research and practice has been widely overlooked by L2 researchers, to date. To fill this gap, the present study made an effort to provide a theoretical analysis of the conceptualizations, scientific background, benefits, and practical techniques to implement SP in the context of L2 education. In so doing, this paper suggests a number of practices through which SP can be integrated into L2 education among which positive psychology (PP) was more highlighted. Additionally, some practical implications were provided for EFL teachers, teacher trainers, students, curriculum designers, and researchers to enhance their knowledge of spirituality and education. In the end, different suggestions for future research were presented to move this research domain forward.

6.
Ann Palliat Med ; 11(9): 2906-2915, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36217619

RESUMO

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for atherosclerosis (AS), but the mechanism is different from classical AS risk factors. Nicotinamide phosphoribosyltransferase (NAMPT) is involved in the pathophysiology of AS via multiple pathways, and its expression is closely related to hypoxia. The association of NAMPT with hypoxia and the risk of cardiovascular morbidity in the patients of OSAHS remains to be defined. Therefore, we carried out this study to investigate the association of NAMPT with hypoxia and the risk of early cardiovascular disease [based on the Framingham risk score (FRS)] in patients with OSAHS. METHODS: A total of 82 patients diagnosed with OSAHS were enrolled in this cross-sectional survey design, along with 18 healthy controls who were age- and gender-matched. The general characteristic parameters including height and weight as well as biochemical parameters including blood glucose and lipid were collected from the subjects. The Framingham vascular risk score calculates the risk of developing vascular disease based on the above indicators. Polysomnography was performed in patients with OSAHS, and blood oxygen saturation and apnea-hypopnea index (AHI) were collected, and patients were grouped by disease extent by AHI. The serum NAMPT level of the research subjects was detected using an enzyme-linked immunosorbent assay. Spearman correlation analysis and multiple linear regression to explore the independent correlations of hypoxia on serum NAMPT activity in OSAHS patients. RESULTS: Serum NAMPT level in patients with OSAHS increased with the severity of the disease. Correlation analysis showed that NAMPT was significantly positively correlated with FRS in patients with OSAHS (r=0.829, P<0.05). Multiple linear regression analysis with FRS as the outcome measure showed that NAMPT activity and minimum blood oxygen saturation were independent associated with the risk of developing cardiovascular disease (ß=0.03, P=0.000; ß=-0.13, P=0.034). Univariate and multivariate regression analyses revealed that hypoxia was significantly associated with NAMPT levels in OSAHS patients, and the oxygen desaturation index (ODI) was independent associated with the expression of NAMPT activity (ß=4.09, P=0.000). CONCLUSIONS: In patients with OSAHS, hypoxia is independently associated with NAMPT. NAMPT increases the risk of cardiovascular morbidity in this population may be influenced by hypoxia.


Assuntos
Doenças Cardiovasculares , Nicotinamida Fosforribosiltransferase , Apneia Obstrutiva do Sono , Glicemia , Doenças Cardiovasculares/complicações , Estudos Transversais , Humanos , Hipóxia/complicações , Lipídeos , Nicotinamida Fosforribosiltransferase/sangue , Oxigênio , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Síndrome
7.
Materials (Basel) ; 15(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36079218

RESUMO

It is necessary to develop new energy technologies because of serious environmental problems. As one of the most promising electrochemical energy conversion and storage devices, the Zn-air battery has attracted extensive research in recent years due to the advantages of abundant resources, low price, high energy density, and high reduction potential. However, the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) of Zn-air battery during discharge and charge have complicated multi-electron transfer processes with slow reaction kinetics. It is important to develop efficient and stable oxygen electrocatalysts. At present, single-function catalysts such as Pt/C, RuO2, and IrO2 are regarded as the benchmark catalysts for ORR and OER, respectively. However, the large-scale application of Zn-air battery is limited by the few sources of the precious metal catalysts, as well as their high costs, and poor long-term stability. Therefore, designing bifunctional electrocatalysts with excellent activity and stability using resource-rich non-noble metals is the key to improving ORR/OER reaction kinetics and promoting the commercial application of the Zn-air battery. Metal-organic framework (MOF) is a kind of porous crystal material composed of metal ions/clusters connected by organic ligands, which has the characteristics of adjustable porosity, highly ordered pore structure, low crystal density, and large specific surface area. MOFs and their derivatives show remarkable performance in promoting oxygen reaction, and are a promising candidate material for oxygen electrocatalysts. Herein, this review summarizes the latest progress in advanced MOF-derived materials such as oxygen electrocatalysts in a Zn-air battery. Firstly, the composition and working principle of the Zn-air battery are introduced. Then, the related reaction mechanism of ORR/OER is briefly described. After that, the latest developments in ORR/OER electrocatalysts for Zn-air batteries are introduced in detail from two aspects: (i) non-precious metal catalysts (NPMC) derived from MOF materials, including single transition metals and bimetallic catalysts with Co, Fe, Mn, Cu, etc.; (ii) metal-free catalysts derived from MOF materials, including heteroatom-doped MOF materials and MOF/graphene oxide (GO) composite materials. At the end of the paper, we also put forward the challenges and prospects of designing bifunctional oxygen electrocatalysts with high activity and stability derived from MOF materials for Zn-air battery.

8.
Reprod Biomed Online ; 45(3): 501-507, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35760666

RESUMO

RESEARCH QUESTION: What is the efficacy of auto-cross-linked hyaluronic acid gel use in preventing adhesion reformation after intrauterine adhesiolysis? DESIGN: This was a single-centre, double-blind randomized controlled trial. RESULTS: In total 171 participants successfully completed the study (84 in the treatment group and 87 in the control group). There was no significant difference in pre-operative variables between the two groups. The primary outcome measure was the adhesion reformation rate at second-look and third-look hysteroscopy. At second-look hysteroscopy, there was no significant difference in adhesion recurrence rate between the treatment group (20.2%, 17/84) and the control group (23.0%, 20/87; P = 0.662). At third-look hysteroscopy, there was also no significant difference in adhesion recurrence rate between the treatment group (9.5%, 8/84) and the control group (11.5%, 10/87; P = 0.675). The secondary outcome measure was the median American Fertility Society (AFS) score, which was not significantly different at second-look hysteroscopy 4 weeks after surgery between the treatment group (0, range 0-4.0) and the control group (0, range 0-4.0; P = 0.475), and at third-look hysteroscopy 8 weeks after surgery between the treatment group (0, range 0-3.5) and the control group (0, range 0-4.0; P = 0.965). Regarding the menstrual flow improvement rate 3 months post-operatively, there was no significant difference between the treatment and control groups (67.9% versus 64.4%; P = 0.630). CONCLUSIONS: The application of auto-cross-linked hyaluronic acid gel does not seem to reduce the incidence and severity of intrauterine adhesion recurrence or affect the menstrual pattern after hysteroscopic removal of mild to moderate intrauterine adhesions.


Assuntos
Ácido Hialurônico , Doenças Uterinas , Estradiol , Feminino , Humanos , Ácido Hialurônico/uso terapêutico , Histeroscopia/efeitos adversos , Gravidez , Aderências Teciduais/etiologia , Aderências Teciduais/prevenção & controle , Aderências Teciduais/cirurgia , Doenças Uterinas/prevenção & controle
9.
J Minim Invasive Gynecol ; 29(7): 871-878, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35439645

RESUMO

STUDY OBJECTIVE: To evaluate whether estrogen therapy can reduce adhesion reformation after hysteroscopic adhesiolysis. DESIGN: A single-center, single blinded, randomized controlled trial. SETTING: A tertiary University Hospital. PATIENTS: A total of 207 patients with mild (American Fertility Society [AFS] score 1-6) and severe (AFS score 7-12) intrauterine adhesion who underwent hysteroscopic adhesiolysis. INTERVENTIONS: Patients were randomized to a treatment group or a control group, stratified according to the preoperative AFS adhesion score. The treatment group received estrogen, and the control group did not. All patients had second-look hysteroscopy at 4 weeks and third-look hysteroscopy at 8 weeks after surgery. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures were adhesion reformation rate and AFS score at third-look hysteroscopy. Secondary outcome measures included adhesion reformation rate and AFS score at second-look hysteroscopy and menstrual pattern improvement rate at 3 months after operation. Among subjects with mild intrauterine adhesion, there was no significant difference between the treatment group and control group with regard to adhesion reformation rate at third-look hysteroscopy (10.6% vs 13.6%), AFS score (mean ± standard deviation) at third-look hysteroscopy (1.1 ± 1.2 vs 1.3 ± 1.2), and menstrual pattern improvement rate at 3-month follow-up (89.4% vs 86.4%). Similarly, among those with severe intrauterine adhesion, there was no significant difference between the treatment group and control group in adhesion reformation rate at third-look hysteroscopy (32.6% vs 26.7%), AFS score (mean ± standard deviation) at third-look hysteroscopy (2.5±2.2 vs 2.7±2.1), and menstrual pattern improvement rate at 3-month follow-up (84.8% vs 73.3%). CONCLUSION: Postoperative estrogen therapy did not appear to reduce the incidence or severity of adhesion reformation, nor did it improve the menstrual pattern, regardless of whether the pre-existing intrauterine adhesion was mild or severe.


Assuntos
Histeroscopia , Doenças Uterinas , Estrogênios/uso terapêutico , Feminino , Humanos , Histeroscopia/efeitos adversos , Gravidez , Estudos Prospectivos , Aderências Teciduais/etiologia , Aderências Teciduais/prevenção & controle , Aderências Teciduais/cirurgia , Doenças Uterinas/complicações
12.
J Interv Cardiol ; 2022: 6025732, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36619817

RESUMO

Background: Evidence regarding the relationship between body mass index (BMI) and cognitive function was limited. Therefore, the objective of this research is to investigate whether BMI is independently related to cognitive function in Chinese patients with atrial fibrillation after adjusting for other covariates. Methods: The present study is a cross-sectional study. A total of 281 patients with atrial fibrillation who were hospitalized at the Affiliated Hospital of Jining Medical University in Shandong Province from January 2021 to November 2021 were included in the study. The target independent variable and the dependent variable were BMI and cognitive function in patients with atrial fibrillation, respectively. The patients' general information, BMI, past history, medication history, and other disease-related data were collected. The Montreal cognitive assessment scale (MoCA) was used to evaluate cognitive function. Results: A total of 244 patients with atrial fibrillation were collected in this study, with an average age of (67.28 ± 10.33) years, of whom 55.3% were male. The average BMI was (25.33 ± 4.27) kg/m2, and the average cognitive function score was (19.25 ± 6.88) points. The results of the smooth curve fitting and threshold effect tests showed that there was a curve correlation between BMI and cognitive function score, and its inflection point was 24.56 kg/m2. To the left of the inflection point, the relationship was significant; the effect size and the confidence interval were 0.43 and 0.01-0.85, respectively. To the right of the inflection point, there was no significant correlation between BMI and cognitive function (P=0.152). Conclusion: When BMI is lower than 24.56 kg/m2, the cognitive function score increases by 0.43 points for each unit increase in BMI in patients with atrial fibrillation. An increase in BMI at this time is a protective factor for cognitive function. Within the normal range of BMI, the higher the BMI in atrial fibrillation patients, the higher the cognitive function score. We encourage atrial fibrillation patients with normal BMI to maintain their current weight.


Assuntos
Fibrilação Atrial , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Fibrilação Atrial/complicações , Índice de Massa Corporal , Fatores de Risco , Estudos Transversais , Cognição
13.
J Pharm Biomed Anal ; 208: 114445, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34763210

RESUMO

The impurity profile of budesonide solution-formulated metered dose inhalation using thermal forced degradation approach was studied intensively in this article. The structural identification of 10 budesonide related impurities was conducted by LC-QTOFMS, and the impurity level in the formulations of different excipients and packing materials were compared using HPLC-UV. Based on our results, the impurities were classified into three groups: (Ⅰ) process impurities, including budesonide impurity A, C and F; (Ⅱ) degradation products, including budesonide impurity E, G, D, 17-carboxylate, and 17-ketone; (Ⅲ) not only process impurities but also degradation products, including budesonide impurity I and L. Budesonide impurity D, 17-carboxylate, 17-ketone and impurity L were found to be the major degradation products of budesonide, and the reaction pathways for the generation of these impurities were speculated. The generation of budesonide impurity D, 17-carboxylate and L was found to be an aerobic oxidation process induced by Al2O3 on the inner surface of aluminum canisters. Furthermore, an in-depth discussion on the proposed impact of the excipients on budesonide degradation, especially on the Al2O3-induced oxidation process, was provided in this article.


Assuntos
Budesonida , Contaminação de Medicamentos , Cromatografia Líquida de Alta Pressão , Excipientes , Oxirredução
14.
J Med Chem ; 64(11): 7468-7482, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34043359

RESUMO

Nowadays, simultaneous inhibition of multiple targets through drug combination is an important anticancer strategy owing to the complex mechanism behind tumorigenesis. Recent studies have demonstrated that the inhibition of histone deacetylases (HDACs) will lead to compensated activation of a notorious cancer-related drug target, signal transducer and activator of transcription 3 (STAT3), in breast cancer through a cascade, which probably limits the anti-proliferation effect of HDAC inhibitors in solid tumors. By incorporating the pharmacophore of the HDAC inhibitor SAHA (vorinostat) into the STAT3 inhibitor pterostilbene, a series of potent pterostilbene hydroxamic acid derivatives with dual-target inhibition activity were synthesized. An excellent hydroxamate derivate, compound 14, inhibited STAT3 (KD = 33 nM) and HDAC (IC50 = 23.15 nM) with robust potency in vitro. Compound 14 also showed potent anti-proliferation ability in vivo and in vitro. Our study provides the first STAT3 and HDAC dual-target inhibitor for further exploration.


Assuntos
Antineoplásicos/química , Inibidores de Histona Desacetilases/química , Histona Desacetilases/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sítios de Ligação , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Meia-Vida , Inibidores de Histona Desacetilases/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/química , Humanos , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/metabolismo , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/antagonistas & inibidores , Estilbenos/química , Estilbenos/metabolismo , Relação Estrutura-Atividade , Vorinostat/química , Vorinostat/metabolismo
15.
Arch Gynecol Obstet ; 304(5): 1345-1351, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33811545

RESUMO

PURPOSE: To examine the association of chronic endometritis (CE) with cervical incompetence (CI) in Chinese women with mid-trimester loss, and the impact of the presence of CE on the outcome of laparoscopic cervical cerclage (LCC). METHODS: This retrospective cohort study included a study group of 293 women with mid-trimester loss due to CI (group I) and a comparison group of 332 women with recurrent first-trimester miscarriage (group II). Immunohistochemical study using CD138 epitope for the diagnosis of CE was completed in all subjects. Pre-conception LCC was undertaken in 247 women in the study group (group I). The study was approved by Institutional Review Board (IRB) (number 2015FXHEC-KY005). RESULTS: The prevalence of CE in group I was 42%, significantly (P < 0.001) higher than that of 23.5% in group II. Among 247 women in group I, there were no significant difference in mid-trimester loss rate, preterm delivery rate and term delivery rate in women with and without CE (2.2, 12.0, 85.8% vs. 1.8, 10.1, 88.1% respectively) and between women with CE treated and not treated with antibiotics prior to conception (2.3, 9.3, 88.4% vs. 2.0, 14.3, 83.7% respectively). CONCLUSIONS: Mid-trimester loss due to cervical incompetence is associated with chronic endometritis; However, the presence or not of CE and whether it was treated with antibiotics prior to conception did not appear to significantly influence the obstetric outcomes of women with CI after LCC.


Assuntos
Cerclagem Cervical , Endometrite , Laparoscopia , Incompetência do Colo do Útero , Endometrite/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , Incompetência do Colo do Útero/epidemiologia , Incompetência do Colo do Útero/cirurgia
16.
Fertil Steril ; 115(6): 1549-1556, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549312

RESUMO

OBJECTIVE: To compare the rates of negative test results for chronic endometritis (CE) between subjects who did and did not receive antibiotic treatment. DESIGN: Prospective, single-blind randomized controlled trial. SETTING: Tertiary hysteroscopic center in a university teaching hospital. PATIENT(S): A total of 132 women with CE confirmed with immunohistochemical study with CD138 epitope. INTERVENTION(S): Women randomized to antibiotic therapy received oral levofloxacin 500 mg and tinidazole 1,000 mg daily for 14 days. Women randomized to the control group did not receive any treatment. A repeated endometrial biopsy was performed 4 to 8 weeks after the initial biopsy to determine whether CE was still present. MAIN OUTCOME MEASURE(S): The rate of negative test results for CE (from positive to negative). RESULT(S): The CE rate of negative test results in the treatment group (89.3%) after one course of antibiotic treatment was significantly higher than that in the control group (12.7%). Among subjects who attempted pregnancy, there was no significant difference in ongoing pregnancy rates and miscarriage rates between the treatment arm (43.2%, 5.4%) and the control arm (25.7%, 14.3%). Among subjects randomized, there was also no significant difference in ongoing pregnancy rates and miscarriage rates between the treatment arm (27.1%, 3.4%) and the control arm (16.4%, 9.1%). CONCLUSION: A course of broad-spectrum oral antibiotic therapy for 14 days is effective in the treatment of CE in >89.8% of cases. However, it is not yet clear whether treatment improved pregnancy outcomes. CLINICAL TRIAL IDENTIFICATION NUMBER: NCT02648698.


Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Técnicas Bacteriológicas , Endometriose/tratamento farmacológico , Aborto Espontâneo/etiologia , Administração Oral , Adulto , Antibacterianos/efeitos adversos , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Pequim , Doença Crônica , Esquema de Medicação , Endometriose/diagnóstico , Endometriose/microbiologia , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento
17.
J Reprod Dev ; 66(6): 493-504, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-32801258

RESUMO

Circular RNA (circRNA) plays a key role in the development and progression of several diseases; however, its role in intrauterine adhesions (IUAs) is not well understood. This study aims to investigate the expression profiles and potential role of circRNA in IUA. RNA-sequencing was performed to screen for abnormally expressed circRNAs in TGF-ß1-induced IUA endometrial stromal cell (ESC) model (IUA group) and an SMAD3 inhibitor, SIS3-treated IUA ESC model (SIS3 group). Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to uncover the key functions and pathways. Interaction networks were constructed and analyzed based on the competing endogenous RNA hypothesis of circRNA. CircRNAs were validated by Sanger sequencing and quantitative polymerase chain reaction (qPCR). Cell proliferation and apoptosis were measured using MTS and flow cytometry, respectively. The protein and mRNA expression levels of fibrosis-related proteins were measured using western blotting and reverse transcription-qPCR, respectively. A total of 66 circRNAs were differentially expressed between the IUA and SIS3 groups. CircPlekha7 was identified as one of the significantly upregulated circRNAs in the SIS3 group. Overexpression of circPlekha7 enhanced apoptosis, decreased the viability of ESCs, and suppressed the expression of α-SMA, collagen I, and SMAD3 in ESCs; whereas knockdown of circPlekha7 exhibited opposite results. Altogether, the results indicate that circPlekha7 plays an anti-fibrotic role in IUA and may serve as a promising prognostic biomarker for patients with IUA. Therefore, overexpression of circPlekha7 could be a potential treatment strategy for IUA.


Assuntos
Apoptose , Proteínas de Transporte/metabolismo , Endométrio/metabolismo , RNA Circular , Células Estromais/metabolismo , Aderências Teciduais/metabolismo , Animais , Proteínas de Transporte/genética , Proliferação de Células , Biologia Computacional , Células Epiteliais/metabolismo , Feminino , Fibrose , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , RNA-Seq , Ratos , Proteína Smad3/antagonistas & inibidores , Fator de Crescimento Transformador beta1/biossíntese , Fator de Crescimento Transformador beta1/metabolismo
18.
Eur J Med Chem ; 199: 112375, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32388278

RESUMO

Deregulation of GP130 in signal transduction is involved in multiple types of human diseases, especially in cancers, indicating that GP130 is an attractive target for cancer therapy. However, GP130 was conventionally considered as an undruggable target thus the discovery of GP130 PPI inhibitors is extremely challenging. By the aid of structure-based drug design, in this study, two series of bazedoxifene based analogues were designed to target GP130 D1 domain and block the IL-6/GP130/STAT3 signaling pathway for antitumor treatment. Most of these designed compounds displayed potent anti-proliferative activity against cancer cells. The representative compound 10a was demonstrated to directly bind to GP130 protein with an affinity (KD) value of 3.8 µM via both SPR and DARTS methods. Subsequently, molecular docking study predicted that 10a targeted D1 domain of GP130 and co-IP assay demonstrated that 10a did not inhibit IL-6R/GP130 interaction, which meant 10a did not bind to the D2 and D3 domains of GP130. Moreover, 10a selectively inhibited JAK2 and STAT3 phosphorylation as well as IL-6 induced STAT3 phosphorylation. 10a effectively inhibited tumor cell viability, migration and promoted apoptosis. Furthermore, 10a effectively suppressed xenograft model tumor growth in vivo. Taken together, this study described a new class of bazedoxifene derived GP130 inhibitors as antitumor agents.


Assuntos
Antineoplásicos/farmacologia , Receptor gp130 de Citocina/antagonistas & inibidores , Descoberta de Drogas , Indóis/farmacologia , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Receptor gp130 de Citocina/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Humanos , Indóis/síntese química , Indóis/química , Masculino , Camundongos , Camundongos Nus , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
19.
Mol Cell Biochem ; 470(1-2): 15-28, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32447720

RESUMO

In this study, we aimed to study the role of miRNAs in intrauterine adhesion (IUA) disease. An IUA cell model was constructed by TGF-ß1. Smad3 inhibitor (SIS3) can inhibit the Smad3 signaling pathway and affect the role of TGF-ß1; thus, it was used to identify the role of Smad3 and related miRNAs in IUA. Cell number significantly increased in the TGF-ß1 group after 72 h and 96 h, respectively, compared with that in the control group (P < 0.05). However, cell proliferation was significantly decreased in the TGF-ß1 + SIS3 group (P < 0.0001). Cell apoptosis was increased in the TGF-ß1 + SIS3 group compared with that in the TGF-ß1 group. Western Blot (WB) analysis suggested that TGF-ß1 treatment could effectively increase the expression of α-SMA, COL1, Smad3, and p-Smad3, which could be inhibited by SIS3 treatment. A total of 235 and 530 differentially expressed miRNAs in the TGF-ß1 + SIS3 group were significantly up- and downregulated compared with those in the TGF-ß1 group, respectively. These differentially expressed miRNAs were enriched in the MAPK and PI3K-AKT pathways. The ten most differentially expressed miRNAs were selected to verify their expressions using quantitative real-time polymerase chain reaction (qPCR). Furthermore, overexpression of rno-miR-3586-3p and rno-miR-455-5p can promote cell proliferation and exacerbate the IUA pathogenic process. However, overexpression of rno-miR-204-3p and rno-miR-3578 can inhibit cell behavior and IUA progression. The above results can provide detailed information for the understanding of IUA molecular mechanisms.


Assuntos
Adesão Celular , MicroRNAs/metabolismo , Proteína Smad3/metabolismo , Aderências Teciduais/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Útero/efeitos dos fármacos , Actinas/metabolismo , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Colágeno Tipo I/metabolismo , Feminino , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Smad3/antagonistas & inibidores , Fator de Crescimento Transformador beta1/antagonistas & inibidores
20.
Reprod Biomed Online ; 40(4): 539-546, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32199799

RESUMO

RESEARCH QUESTION: Does placing an intrauterine balloon for different durations (7, 14 or 28 days) affect the recurrence of intrauterine adhesions after hysteroscopic adhesiolysis? DESIGN: Prospective randomized control trial involving 138 patients recruited over a 12-month period and followed up post-operatively for 15 months. The primary outcome measure was the rate of adhesion reformation at third-look hysteroscopy. RESULTS: At third-look hysteroscopy, 8 weeks after the initial hysteroscopy, the adhesion recurrence rate in women who had an intrauterine balloon for 28 days (20%) was significantly (P < 0.01) lower than that of women who had the balloon for 14 days (55%) or 7 days (36.8%). CONCLUSIONS: Placing an intrauterine balloon for 28 days instead of 7 or 14 days after hysteroscopic adhesiolysis resulted in a greater reduction in the recurrence rate of adhesions. However, the study was underpowered to address whether the ongoing pregnancy rate could be improved by keeping the balloon in the uterine cavity for a longer period of time.


Assuntos
Histeroscopia , Doenças Uterinas/cirurgia , Útero/cirurgia , Adulto , Feminino , Humanos , Estudos Prospectivos , Recidiva , Prevenção Secundária/métodos , Fatores de Tempo , Aderências Teciduais/prevenção & controle , Aderências Teciduais/cirurgia , Resultado do Tratamento , Doenças Uterinas/prevenção & controle
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