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Monochlorodifluoromethane (HCFC-22) has been identified as a significant contributor to the depletion of the Earth's ozone layer, garnering considerable attention within the scientific community. Consequently, the investigation of Freon degradation has become a central focus of current research efforts. In this study, we opted to employ catalytic hydrolysis as it offers numerous advantages for the degradation of HCFC-22. Specifically, we prepared ZnO/ZrO2 catalysts with hexahedral rod-like structures through citric acid complexation. We examined the impact of various preparation conditions (such as the molar ratio of ZnO to ZrO2, calcination temperature, and calcination time) as well as catalytic hydrolysis conditions (including the amount of catalyst, total flow rate, and catalytic hydrolysis temperature) on the hydrolysis rate of HCFC-22. Characterization of the catalysts was performed using techniques such as XRD, SEM, EDS, TG-DTG, FTIR, N2 adsorption-desorption, CO2-TPD, and NH3-TPD. Our experimental findings revealed the optimal preparation conditions: a catalytic hydrolysis temperature of 100 °C, a molar ratio of ZnO to ZrO2 of 0.7, a water bath temperature of 90 °C, a roasting temperature of 400 °C, and a roasting time of 4 h. At a catalytic hydrolysis temperature of 100 °C, the hydrolysis rate of HCFC-22 reached 99.81%, with the main hydrolyzed products being HCl, HF, and CO2.
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Clorofluorocarburos de Metano , Óxidos , Óxido de Zinc , Temperatura , Óxidos/química , Oxidación-Reducción , Hidrólisis , Dióxido de CarbonoRESUMEN
Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.
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The pathogenesis of Alzheimer's disease (AD) involves multiple pathophysiological processes. Oxidative stress is a major cause of AD-associated neuronal injury. The current research was designed to examine whether a novel (-)-meptazinol-serotonin hybrid (Mep-S) with potent antioxidant activity and additional inhibitory properties for acetylcholinesterase (AChE) activity could attenuate oxidative neuronal damage and cognitive deficits. In human SH-SY5Y cells, Mep-S suppressed H2O2-induced apoptosis by restoring mitochondrial membrane potential and inhibiting caspase-3 activation. Meanwhile, it attenuated oxidative stress elicited by H2O2 through lessening generation of reactive oxygen species as well as enhancing production of glutathione (GSH) and activity of superoxide dismutase (SOD). Mechanistically, Mep-S promoted nuclear translocation of a transcription factor nuclear factor E2-related factor-2 (Nrf2) in H2O2-challenged cells. This effect was accompanied by reduction in Kelch-like ECH-associated protein-1 (Keap1) levels as well as augmentation of Akt phosphorylation and expression of heme oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1 (NQO-1). Molecular docking analysis revealed that Mep-S may disrupt the protein-protein interactions between Keap1 and Nrf2. In an in vivo mouse model, Mep-S attenuated scopolamine-caused cognitive deficits with inhibition of apoptotic neuronal death and brain AChE activity. Furthermore, the scopolamine-induced impairment of total antioxidant capacity and reduction in SOD1, SOD2, and γ-glutamate-cysteine ligase expression in the brain were counteracted by Mep-S, accompanied by decreased Keap1 levels, increased Akt catalytic subunit and Nrf2 phosphorylation, and decreased Nrf2, HO-1, and NQO-1 expression. Collectively, our results suggest that Mep-S ameliorates apoptotic neuronal death and memory dysfunction associated with oxidative stress by regulating the Nrf2/antioxidant enzyme pathway through inactivating Keap1 and phosphorylating Nrf2 via Akt activation. Therefore, Mep-S may be a potential lead for multitarget neuroprotective agents to treat AD-like symptoms.
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Enfermedad de Alzheimer , Meptazinol , Neuroblastoma , Ratones , Humanos , Animales , Antioxidantes/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Serotonina , Peróxido de Hidrógeno/farmacología , Acetilcolinesterasa/metabolismo , Simulación del Acoplamiento Molecular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Glutatión/metabolismo , Trastornos de la Memoria , Derivados de Escopolamina/farmacología , Hemo-Oxigenasa 1/metabolismoRESUMEN
Environmental responsibility information disclosure is an important means for high-polluting enterprises to win the recognition and support of external stakeholders. This study constructs a fixed-effects model based on panel data of 951 Chinese high-polluting enterprises in Shanghai and Shenzhen A-shares from 2015 to 2019 to verify the effect of environmental responsibility information disclosure on enterprise market competitiveness and the mediating effect of cooperative resources. The sample enterprises are further divided into state-owned and non-state-owned enterprises, and the results show that environmental responsibility information disclosure is more effective for non-state-owned enterprises to obtain cooperative resources and thus enhance market competitiveness. This study highlights the effectiveness of environmental responsibility information disclosure in strengthening the enterprise market competitiveness from the perspective of stakeholders in the supply chain, which has certain inspirations and empirical implications for enterprises to strengthen their environmental responsibility information disclosure system.
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Conservación de los Recursos Naturales , Revelación , ChinaRESUMEN
Introduction: Adverse drug reactions (ADRs) represent a public health problem worldwide that deserves attention due to the impact on mortality, morbidity, and healthcare costs. Drug-drug interactions (DDIs) are an important contributor to ADRs. Most of the studies focused only on potential DDIs (pDDIs), while the detailed data are limited regarding the ADRs associated with actual DDIs. Methods: This retrospective study evaluated ADRs reported between 2011 and 2020 in a tertiary hospital. The causality and severity of ADRs were evaluated through the Naranjo Algorithm and Hartwig's scale, respectively. Preventability classification was based on the modified Schoumock and Thornton scale. For ADRs with at least two suspected drugs, pDDIs were identified according to the Lexi-Interact. We further checked whether the ADR description in the reports corresponded to the clinical consequences of the pDDIs. Results: A total of 1,803 ADRs were reported, of which 36.77% ADRs were classified as mild, 43.26% as moderate, and 19.97% as severe. The assessment of causality showed that the distributions of definite, probable, and possible categories were 0.33%, 58.68%, and 40.99%, respectively. A total of 53.97% of ADRs were identified as preventable ADRs, while 46.03% were recognized as unpreventable. The severity of ADRs was significantly correlated with age, the number of suspected drugs and preventability. Antimicrobial agents were the most common implicated pharmacological group, and the most frequently affected system was the gastrointestinal system. Considering individual drugs, aspirin was the most frequently reported drug. Among 573 ADRs with at least two suspected drugs, 105 ADRs were caused by actual DDIs, of which only 59 and 6 ADRs were caused by actual DDIs in category D and X, respectively. The most frequent drugs involved in actual DDIs of category D were aspirin and heparin, with the majority of ADRs being gastrointestinal bleeding. Conclusion: This study analyzed the pattern of ADRs in detail and obtained clinical evidence about ADRs associated with actual DDIs. These findings may be useful to compare patterns between different centers and to design preventive strategies for ADRs. Continuous education and training should be provided for physicians regarding the knowledge and recognition of ADRs associated with DDIs.
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Backgrounds: Uterine corpus endometrial carcinoma (UCEC) is one of the greatest threats on the female reproductive system. The aim of this study is to explore the inflammation-related LncRNA (IRLs) signature predicting the clinical outcomes and response of UCEC patients to immunotherapy and chemotherapy. Methods: Consensus clustering analysis was employed to determine inflammation-related subtype. Cox regression methods were used to unearth potential prognostic IRLs and set up a risk model. The prognostic value of the prognostic model was calculated by the Kaplan-Meier method, receiver operating characteristic (ROC) curves, and univariate and multivariate analyses. Differential abundance of immune cell infiltration, expression levels of immunomodulators, the status of tumor mutation burden (TMB), the response to immune checkpoint inhibitors (ICIs), drug sensitivity, and functional enrichment in different risk groups were also explored. Finally, we used quantitative real-time PCR (qRT-PCR) to confirm the expression patterns of model IRLs in clinical specimens. Results: All UCEC cases were divided into two clusters (C1 = 454) and (C2 = 57) which had significant differences in prognosis and immune status. Five hub IRLs were selected to develop an IRL prognostic signature (IRLPS) which had value in forecasting the clinical outcome of UCEC patients. Biological processes related to tumor and immune response were screened. Function enrichment algorithm showed tumor signaling pathways (ERBB signaling, TGF-ß signaling, and Wnt signaling) were remarkably activated in high-risk group scores. In addition, the high-risk group had a higher infiltration level of M2 macrophages and lower TMB value, suggesting patients with high risk were prone to a immunosuppressive status. Furthermore, we determined several potential molecular drugs for UCEC. Conclusion: We successfully identified a novel molecular subtype and inflammation-related prognostic model for UCEC. Our constructed risk signature can be employed to assess the survival of UCEC patients and offer a valuable reference for clinical treatment regimens.
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BACKGROUND: The reliability of Criteria for Assessing Prescription Quality in Chinese Hospitals (CAPQCH) has never been rigorously verified. This study was designed to verify the reliability of the CAPQCH among pharmacists in China. METHODS: Fourteen pharmacists, 5 from hospitals and 9 from the communities were recruited. We randomly selected 200 prescriptions, and made the testing prescriptions including appropriate and inappropriate testing prescriptions. Pharmacists assessed these testing prescriptions according to criteria in CAPQCH. Three test sets (Set 1, Set 2, and Set 3) were evaluated at 6-month intervals. Before administration of Set 3, pharmacists were informed that achievement on Set 3 would be reflected in their performance appraisal. We also evaluated the performance based on prescription comments before and after combining several confusing criteria. Cohen's Kappa statistic, Fleiss' Kappa statistic, and accuracy were employed to evaluate reliability among pharmacists. RESULTS: Median values of Cohen's Kappa were 0.61 in Set 1, 0.66 in Set 2, and 0.80 in Set 3; reliability is thus substantial. Our data indicate no significant differences between Set 1 and Set 2, whereas Set 3 indicates significantly improved performance. Moreover, combinations of confusing criteria contributed little to improvement of performance in prescription comments. CONCLUSION: Our results verified the reliability of CAPQCH application by working pharmacists. Adding performance based on prescription comments to personal appraisals was effective in improving the quality of prescription comments. These findings may be useful when future modification of the CAPQCH is considered. Moreover, this study contributes to improving the understanding of the prescription assessment situation in China.
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Farmacéuticos , Prescripciones , Hospitales , Humanos , Prescripción Inadecuada , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disease that is associated with recurrent pregnancy loss. It is still controversial whether the presence of antiphospholipid antibodies (aPL) in the serum of patients with in vitro fertilization-embryo transfer (IVF-ET) has a negative effect on the outcomes. In view of the discrepancies, a meta-analysis of the published data was performed to explore the relationship of aPL and IVF-ET outcomes. METHODS: We searched for all published articles indexed in PubMed, Web of Science, and Cochrane Library, which were retrieved up to April, 2021. A total of 921 studies were yielded, of which 6 finally met the inclusion criteria. We carried out the meta-analysis by pooling results of these studies with Review Manager 5.3 software. The effect index was measured with 95% confidence intervals (CIs) of the relative risks (RRs). RESULTS: Six eligible studies were included in this meta-analysis, involving 3214 patients. Our results showed that positive aPL was not associated with decreased clinical pregnancy rate (RR 0.97; 95% CI 0.91-1.04). There was no correlation between positive aPL and increased miscarriage risk (RR 1.22; 95% CI 0.94-1.58). Only 5 of the 6 studies referred to live birth rate, but still no association was found between them (RR 0.95; 95% CI 0.81-1.11). CONCLUSIONS: The results showed that the presence of positive aPL neither decreased clinical pregnancy rate and live birth rate, nor increased miscarriage rate in women undergoing IVF, which is differed from the opinion of clinical practice. More prospective studies with high quality and larger sample size are needed to evaluate the relationship between positive aPL and outcomes of IVF-ET.
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Aborto Habitual , Resultado del Embarazo , Anticuerpos Antifosfolípidos , Femenino , Fertilización In Vitro/métodos , Humanos , Nacimiento Vivo , Embarazo , Resultado del Embarazo/epidemiología , Índice de Embarazo , Estudios ProspectivosRESUMEN
In some cases of spontaneous miscarriage (SM), the exact etiology cannot be determined. Autophagy, which is responsible for cellular survival under stress conditions, has also been implicated in many diseases. Recently, it is also surmised to be correlated with SM. However, the detailed mechanism remains elusive. In fact, there are several essential steps during pregnancy establishment and maintenance: trophoblasts invasion, placentation, decidualization, enrichment and infiltration of decidua immune cells (e.g., natural killer, macrophage and T cells). Accordingly, upstream molecules and downstream effects of autophagy are discussed in these processes, respectively. Of note, autophagy regulates the crosstalk between these cells at the maternal-fetal interface as well. Aberrant autophagy is found in villi, decidual stromal cells, peripheral blood mononuclear cells in SM patients, although the findings are inconsistent among different studies. Furthermore, potential treatments targeting autophagy are included, during which rapamycin and vitamin D are hot-spots in recent literatures. To conclude, a moderately activated autophagy is deeply involved in pregnancy, suggesting that autophagy should be a regulator and promising target for treating SM.
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Aborto Espontáneo , Autofagia , Decidua , Femenino , Humanos , Leucocitos Mononucleares , Embarazo , TrofoblastosRESUMEN
Lipid metabolism is important in various cancers. However, the association between lipid metabolism and uterine corpus endometrial carcinoma (UCEC) is still unclear. In this study, we collected clinicopathologic parameters and the expression of lipid metabolism-related genes (LMRGs) from the Cancer Genome Atlas (TCGA). A lipid metabolism-related risk model was built and verified. The risk score was developed based on 11 selected LMRGs. The expression of 11 LMRGs was confirmed by qRT-PCR in clinical samples. We found that the model was an independent prediction factor of UCEC in terms of multivariate analysis. The overall survival (OS) of low-risk group was higher than that in the high-risk group. GSEA revealed that MAPK signaling pathway, ERBB signaling pathway, ECM receptor interaction, WNT pathway, and TGF-ß signaling pathway were enriched in the high-risk group. Low-risk group was characterized by high tumor mutation burden (TMB) and showed sensitive response to immunotherapy and chemotherapy. In brief, we built a lipid metabolism gene expression-based risk signature which can reflect the prognosis of UCEC patients and their response to chemotherapeutics and immune therapy.
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Correction for 'Facile synthesis of near-infrared bodipy by donor engineering for in vivo tumor targeted dual-modal imaging' by Feifei An et al., J. Mater. Chem. B, 2021, 9, 9308-9315, DOI: 10.1039/D1TB01883C.
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GPR120 is implicated in the regulation of glucose and lipid metabolism, and insulin resistance. In the current study, we aimed to investigate the role of GPR120 in polycystic ovary syndrome (PCOS). With the adoption of dehydroepiandrosterone, a rat model was established to simulate PCOS in vitro. mRNA and protein expression levels of GPR120 were measured using RT-qPCR and western blot, respectively. In addition, expression levels of testosterone, estradiol, luteinizing hormone and follicle-stimulating hormone, serum total cholesterol and triglyceride were assessed using the corresponding kits. Moreover, haematoxylin and eosin staining was used to detect pathological changes in ovary or liver and oil red staining was utilized to evaluate lipid accumulation. In the present study, GPR120 was downregulated in plasma, liver and ovary in the PCOS rat model. In addition, the GPR120 agonist regulated lipid metabolism in the liver and weight in the PCOS rat model. Furthermore, the GPR120 agonist decreased insulin resistance in the PCOS rat model but improved the ovarian function. It is suggested that GPR120 plays a vital role in suppressing insulin resistance, regulating ovary function and decreasing lipid accumulation in the liver, demonstrating that targeting GPR120 could be an effective method for the improvement of PCOS.
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Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Receptores Acoplados a Proteínas G/agonistas , Animales , Femenino , Hormona Folículo Estimulante/farmacología , Humanos , Insulina , Hormona Luteinizante , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/genética , Ratas , Testosterona , TriglicéridosRESUMEN
Bodipy is one of the most popular dyes for bioimaging, however, a complicated synthetic protocol is needed to create and isolate ideal near-infrared (NIR) emissive Bodipy derivatives for optical bioimaging. It is noticed that the donor species impact the wavelength when the π-conjugation system of green light emissive Bodipy is elongated via a one-step reaction. Herein, several Bodipy dyes bearing different common donors are synthesized. Their optical properties confirm that both absorption and emission peaks of the synthesized Bodipy could be tuned to NIR wavelength by using stronger donors via a facile reaction. The synthesized monocarboxyl Bodipy could conjugate with aminated PEG to yield an amphiphilic polymer, which further self-assembles into a NIR nanoparticle (NP). The NIR NP exhibits preferential tumor accumulation via the enhanced permeation and retention (EPR) effect, making it useful for tumor diagnosis by both fluorescence imaging and photoacoustic tomography.
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Adenocarcinoma del Pulmón/diagnóstico por imagen , Compuestos de Boro/síntesis química , Ingeniería Química , Neoplasias/diagnóstico por imagen , Células A549 , Animales , Humanos , Ratones , Ratones Desnudos , Neoplasias Experimentales/diagnóstico por imagenRESUMEN
BACKGROUND: Inappropriate perioperative medications among elderly patients increase the risk of adverse events and undermine surgical outcomes. This study aimed to assess the prevalence of high-risk medications in elderly surgical patients and verify the effectiveness of a new-developed high-risk perioperative medications (HRPOMs) list for the elderly. METHODS: A cross-sectional, single-center study was conducted at Jinshan Hospital of Fudan University. A total of 810 elderly surgical patients were included in the study. The HRPOMs list was applied to patients' data to identify the HRPOMs including chronic medications and medications related to surgery. RESULTS: A total of 2113 HRPOMs were identified in 810 patients who fulfilled the inclusion criteria. Of these, 1067 (50.5%) involved medications related to surgery, and 982 (46.5%) involved chronic medications. The prevalence of HRPOM exposure, which was defined as at least one HRPOM was 76.3%. Patients that were 70 years or older (adjusted odds ratio [AOR] =2.118, 95% confidence interval [CI], 1.420~3.159), hospitalized over two weeks (AOR =4.192, 95% CI, 1.493~11.771), with more than 2 distinct diagnoses (AOR =3.407, 95% CI, 2.224~5.220) and with 16 or more medications during hospitalization were more likely to be exposed to HRPOMs. Patients who underwent surgeries of Grade IV were at 1.73 increased odds of HRPOM exposure compared with those who received surgeries of Grade III or lower (P=0.071). CONCLUSION: HRPOMs are more common in patients of 70 years or older, with 3 or more distinct diagnoses, with 16 or more medications and hospitalized for 15 days or longer. Our study showed the validity of the HRPOMs list in the perioperative medication review for the elderly and may induce further research to reveal the impact of HRPOMs upon the surgical outcomes of the elderly.
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Hospitalización/estadística & datos numéricos , Prescripción Inadecuada/estadística & datos numéricos , Periodo Perioperatorio/estadística & datos numéricos , Factores de Edad , Anciano , Anciano de 80 o más Años , China , Estudios Transversales , Femenino , Humanos , Tiempo de Internación , Masculino , Polifarmacia , Prevalencia , Índice de Severidad de la EnfermedadRESUMEN
A successful pregnancy requires sufficient decidualization of endometrial stromal cells (ESCs). CD82, a metastasis suppressor, is a critical regulator for trophoblast invasion but the effect in decidualization was largely unknown. Here we reported that there was a high level of CD82 in DSC by the immunohistochemistry staining and flow cytometer analysis. Stimulation with prostaglandin E2 (PGE2) elevated the expression of CD82 in ESCs. In contrast, celecoxib, a selective COX-2 inhibitor, significantly downregulated the expression of CD82 in decidual stromal cells (DSCs). Bioinformatics analysis and further research showed that recombinant human interleukin (IL)-1ß protein (rhIL-1ß) upregulated CD82 in ESCs. Of note, blocking IL-1ß signaling with anti-human IL-1ß neutralizing antibody could reverse the stimulatory effect of PGE2 on CD82 in ESCs. Silencing CD82 resulted in the decease of the decidualization markers PRL and IGFBP1 mRNA levels in DSCs. More importantly, we observed rhIL-1ß also upregulated the expression of COX-2, and the upregulation of PRL and IGFBP1 induced by rhIL-1ß could be abolished by celecoxib in ESCs or CD82 deficiency in DSCs. This study suggests that CD82 should be a novel promotor for decidualization under a positive regulation of the COX-2/PGE2/IL-1ß positive feedback loop.
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Decidua , Proteína Kangai-1 , Células del Estroma , Células Cultivadas , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Decidua/metabolismo , Femenino , Humanos , Interleucina-1beta/metabolismo , Proteína Kangai-1/genética , Proteína Kangai-1/metabolismo , Embarazo , Células del Estroma/metabolismo , Trofoblastos/metabolismoRESUMEN
Background: It has been reported that long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis. However, their roles in ovarian cancer (OC) remain to be elucidated. The aim of this study was to uncover the function and underlying mechanisms of PCAT6 in OC. Methods: The expression pattern of PCAT6 in OC was analyzed in the GSE137238, GSE143897 and Gene Expression Profile Interactive Analysis (GEPIA) datasets. Kaplan-Meier Plotter online software was used for survival analysis. Loss-of-function assays and gain-of-function assays were used to assess the function of PCAT6 in OC development. Moreover, small-RNA sequencing, bioinformatic analysis, luciferase assays and rescue experiments were carried out to clarify the potential mechanism of PCAT6 in OC. Results: PCAT6 expression was significantly increased in OC tissues and positively correlated with advanced stages and with poor overall survival, progression-free survival and post-progression survival. Knockdown of PCAT6 in A2780 and SKOV3 cells inhibited OC cell proliferation, migration and invasion. In contrast, Overexpression of PCAT6 exerted the opposite effects on OC cells. Notably, PCAT6 bound to miR-143-3p and affected the expression of transforming growth factor (TGF)-ß-activated kinase 1 (TAK1). Subsequent rescue assays confirmed that upregulation of miR-143-3p decreased the PCAT6 overexpression-induced promotion of proliferation, migration and invasion. Moreover, downregulation of miR-143-3p reversed the PCAT6 knockdown-induced inhibition of proliferation, migration, and invasion. Conclusions: Our findings demonstrate that PCAT6 plays an oncogenic role in OC and may be useful as a therapeutic target for OC.
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BACKGROUND: Anti-phospholipid antibodies (aPL) have been reported to be associated with repeated implantation failure (RIF), but the mechanism remains controversial. Endometrial receptivity is well known to be crucial for embryo implantation. This study aims to investigate the effect of aPL on endometrial receptivity in RIF women with positive aPL. METHODS: Sixty-four infertile women with normal menstrual cycles were enrolled. The control group comprised 32 pregnant women with negative aPL who conceived successfully after their first in vitro fertilization-embryo transfer (IVF-ET) cycle, and the RIF group comprised 32 women with positive aPL. Endometrial biopsy samples were collected seven days after the luteinizing hormone surge (LH + 7). The expression of LIF and HOXA10 was evaluated by immunohistochemistry, qRT-PCR and Western blot. Endometrial pinopode development was examined by scanning electron microscopy. RESULTS: The mRNA expression of LIF and HOXA10 in the RIF group was significantly decreased compared with that in the control group during the implantation window. The immunohistochemistry and Western blot results confirmed these findings. Then, ultrastructural analyses of endometrial cells showed fewer pinopode processes, a more atypical morphology and increased atrophy in the RIF group compared with the control group, and these results were statistically significant. CONCLUSION: aPL positivity may inhibit the expression of LIF and HOXA10 in the endometrium and influence pinopode development. Our findings suggest that positivity for aPL is associated with impaired endometrial receptivity, which results in the development of RIF.
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Anticuerpos Antifosfolípidos/sangre , Implantación del Embrión , Endometrio/metabolismo , Proteínas Homeobox A10/metabolismo , Factor Inhibidor de Leucemia/metabolismo , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Transferencia de Embrión , Endometrio/ultraestructura , Femenino , Fertilización In Vitro , Proteínas Homeobox A10/genética , Humanos , Infertilidad Femenina/terapia , Factor Inhibidor de Leucemia/genética , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Peptide drugs provide promising regimes in bladder cancer. In order to identify potential bioactive peptides involved in bladder cancer, we performed the present study. METHODS: Liquid chromatography/mass spectrometry assay was used to compare the endogenous peptides between bladder cancer and normal control. The potential biological functions of these dysregulated peptides are assessed by GO analysis and KEGG pathway analysis of their precursors. The SMART and UniProt databases are used to identify the sequences of the dysregulated peptides located in the functional domains. The Open Targets Platform database was used to investigate the precursors related to metabolic diseases. RESULTS: A total of 9 up-regulated peptides and 110 down-regulated peptides in bladder cancer compared with normal control were identified (fold change > 1.2, P < 0.05). The MW of these dysregulated peptides ranged from 500 Da to 2500 Da and the MW of all identified peptides was below 3500 Da. The GO and KEGG pathway analysis indicated that these dysregulated peptides could play an important role in bladder cancer. Our further analysis revealed that 45HFNPRFNAHGDAN 57 derived from LGALS1 and those peptides derived from P4HB and SERPINA1 might be the promising diagnostic biomarkers and therapeutic targets of bladder cancer. CONCLUSION: In the present study, we have identified the profile of the peptides significantly dysregulated in bladder cancer. Moreover, using bioinformatic analysis, we found the peptides derived from LGALS1, P4HB and SERPINA1 could be the promising diagnostic biomarkers and therapeutic targets of bladder cancer.
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OBJECTIVE: To analyze the functions of the two extracellular loops of occludin in the tight junction of TM4 cells in mice. METHODS: Using genetic engineering, we separately or simultaneously deleted two extracellular loops of occludin, cloned the three occludin genes without extracellular loops into the pcDNA3.1 expression vector, and transfected them into TM4 cells. Then we determined the expression of occludin by RT-PCR and Western blot, and analyze the effects of the extracellular loops of occludin on the tight junction of the TM4 cells with the in vitro cell line model. RESULTS: The results of sequencing showed that the expression vector of pcDNA3.1 - occludin Δ OCC1, pcDNA3.1 - occludin Δ OCC2 and pcDNA3.1 - occludin Δ OCC1 + OCC2 was constructed successfully. The mRNA and protein expressions of occludin in the non-extracellular loop groups were significantly higher than in the control group. Both the extracellular loops of occludin increased the tight junction of the TM4 cells. The macromolecular permeability in the TM4 cells was significantly lower in the pcDNA3.1 - occludin Δ OCC1 than in the pcDNA3.1 - occludin Δ OCC2 group (P < 0.05), indicating a higher impact of the second than the first extracellular loop on the tight junction of the TM4 cells. CONCLUSIONS: Both of the two extracellular loops of occludin can affect the tight junction of TM4 cells, the second even more significantly than the first one.
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Ocludina/genética , Eliminación de Secuencia , Células de Sertoli/patología , Uniones Estrechas/patología , Animales , Masculino , Ratones , Permeabilidad , ARN MensajeroRESUMEN
The aim of this study was to investigate the characteristics of medication errors (MEs) and adverse drug reactions (ADRs) using data from the spontaneous reporting system, which is helpful to understand the actual situation of MEs in China. Data from 2015 in a south distinct in Shanghai were gathered from the spontaneous reporting system and analyzed. The general information, cause of errors, severity, primary diseases, involved system and organs, symptoms, and suspected drugs were investigated. A total of 1290 adverse drug events (ADEs), including 1079 ADRs and 211 MEcs (MEs causing ADE), were reported. Older patients suffered from both ADRs and MEcs (age distribution and dosage form were different between ADRs and MEcs). The main causes of errors were inappropriate usage and dosage of drugs and inappropriate indication selection. Most ADR and MEc cases were mild; the possibility of developing a severe adverse event was quite low. The distribution of the top 10 system and organs, and symptoms involved was significantly different between ADRs and MEcs, with J01 drugs (antibacterials for systemic use) being the leading cause in both. Our results suggested that a direct analysis of data from the spontaneous reporting system is a reliable, and convenient method to investigate MEs and ADRs, despite the existing limitations, and contributes to further understanding the current situation of MEs and ADRs in China.