RESUMEN
OBJECTIVE: The potential mechanisms linking social participation and depressive symptoms in Chinese individuals with multimorbidity are not yet fully understood. This study aims to explore how cognitive function and activities of daily living (ADLs) mediate the relationship between social participation and depressive symptoms in individuals with multimorbidity. METHODS: We selected 3782 participants with multimorbidity from the 2018 China Health and Retirement Longitudinal Study. Data related to social participation, cognitive function, ADLs, and depressive symptoms were extracted. Regression and Bootstrap analyses were used to explore the sequential mediating effects of social participation, cognitive function, ADLs, and depressive symptoms. RESULTS: (1) There was a significant correlation between social participation, cognitive function, activities of daily living, and depressive symptoms (p < 0.01). (2) Social participation directly affected depressive symptoms (ß = -0.205, p < 0.05). (3) Cognitive function (ß = -0.070, p < 0.01) and activities of daily living (ß = -0.058, p < 0.01) played separate mediating roles in the effect of social participation on depressive symptoms. (4) Cognitive function and activities of daily living had a chain-mediated role in the relationship between social participation and depressive symptoms in patients with multimorbidity (ß = -0.020, p < 0.01). CONCLUSION: A chained mediating effect was found between cognitive function, ADLs, social participation, and depressive symptoms in patients with multimorbidity. Social participation was found to improve the cognitive function of patients with multimorbidity, which in turn enhanced their daily life activities and ultimately alleviated their depressive symptoms.
Asunto(s)
Actividades Cotidianas , Cognición , Depresión , Multimorbilidad , Participación Social , Humanos , Actividades Cotidianas/psicología , Participación Social/psicología , Masculino , Femenino , Depresión/epidemiología , Depresión/psicología , Anciano , China/epidemiología , Estudios Longitudinales , Persona de Mediana Edad , Anciano de 80 o más AñosRESUMEN
The impact of hepatitis B virus (HBV) infection on the progression of coronavirus disease 2019 (COVID-19) disease remains controversial. We aimed to investigate whether pre-existing chronic HBV (CHB) infection and therapy with anti-HBV nucleos(t)ide analogs (NAs) influence the clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. In this study, clinical information was collected via a questionnaire from patients with COVID-19, and their clinical symptoms were quantitatively assessed for comparative analyses. Additionally, hepatitis B-related laboratory data were collected for CHB patients. Propensity score matching (PSM) was used to minimize confounding biases. A total of 785 patients with COVID-19 were included in the cohort, of which 387 were identified as being infected with CHB infection and they were categorized as being in the immune control or clearance phase. After PSM, the CHB group (n = 222) had a shorter duration of fever and disease course, milder clinical symptoms, and lower incidence of pneumonia than the non-CHB group (n = 222) after Omicron variant infection (p < 0.05). After the adjustment of confounding factors, CHB patients showed a lower risk of prolonged fever, severe clinical symptoms, and pneumonia (p < 0.05). However, there were no statistically significant differences in the clinical symptoms and incidence of pneumonia between CHB patients who received and did not receive NAs, or CHB patients who received tenofovir disoproxil fumarate and entecavir (p > 0.05). In conclusion, our findings suggest that the crosstalk of anti-HBV immunity may contribute to the alleviated symptoms of SARS-CoV-2 Omicron variants infection in the CHB patients, independent of anti-HBV NA therapy.
Asunto(s)
COVID-19 , Hepatitis B Crónica , Humanos , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/diagnóstico , SARS-CoV-2 , Antivirales/uso terapéutico , Virus de la Hepatitis BRESUMEN
Background: This study evaluated the effectiveness of the smartphone-based WeChat platform in reducing the ischemia time of ST-segment elevation myocardial infarction (STEMI). Methods: A total of 198 STEMI patients who underwent primary percutaneous coronary intervention (PCI) from January 2022 to August 2022 in our hospital were enrolled in this retrospective cohort study. Patients were divided into two groups according to whether their electrocardiograms (ECGs) were posted on the WeChat platform. The two groups were compared for the following: diagnosis time of first ECG, time from first medical contact (FMC) to catheterization laboratory (CL) activity, bypass emergency department (ED) or critical care unit (CCU), time of door to wire, time of door to balloon, time of FMC to wire, heart failure during hospitalization, cardiogenic shock during hospitalization, malignant arrhythmia during hospitalization, death during hospitalization, total hospital cost, and length of stay. Results: The diagnosis time for the first ECG was 10.05 ± 3.30 mins in the control group and 2.50 ± 0.82 mins in the WeChat group (p < 0.05). The time from FMC to CL activity was significantly shorter in the WeChat group compared to the control group (p < 0.05). None of the control group patients bypassed the ED, compared to 80 (80%) of patients in the WeChat group (p < 0.05). The time from door to wire was 60.22 ± 12.73 mins in the WeChat group and 92.56 ± 20.23 mins in the control group (p < 0.05). The time of FMC to wire was also significantly shorter in the WeChat group than in the control group (p < 0.05). The WeChat group had a significantly lower rate of heart failure during hospitalization than the control group (p < 0.05). However, the two groups showed no significant differences for cardiogenic shock during hospitalization, malignant arrhythmia during hospitalization, death during hospitalization, total hospital cost, and length of stay. Conclusions: The smartphone-based WeChat platform demonstrated high efficacy and accessibility in reducing the ischemia time for STEMI patients. Our results indicate that social media platforms such as WeChat could be a useful approach for improving the prognosis of cardiovascular disease.
RESUMEN
BACKGROUND: Sepsis is a life-threatening organ dysfunction syndrome resulted from severe infection with high morbidity and mortality. Cluster of differentiation 38 (CD38) is a multifunctional type II transmembrane glycoprotein widely expressed on the surface of various immunocytes membranes that mediates host immune response to infection and plays an important role in many inflammatory diseases. Daphnetin (Daph), isolated from the daphne genus plant, is a natural coumarin derivative that possesses anti-inflammatory and anti-apoptotic effects. The current study aimed to investigate the role and mechanism of Daph in alleviating lipopolysaccharide (LPS)-induced septic lung injury, and to explore whether the protective effect of Daph in mice and cell models was related to CD38. METHODS: Firstly, network pharmacology analysis of Daph was performed. Secondly, LPS-induced septic lung injury in mice were treated with Daph or vehicle control respectively and then assessed for survival, pulmonary inflammation and pathological changes. Lastly, Mouse lung epithelial cells (MLE-12 cells) were transfected with CD38 shRNA plasmid or CD38 overexpressed plasmid, followed by LPS and Daph treatment. Cells were assessed for viability and transfection efficiency, inflammatory and signaling. RESULTS: Our results indicated that Daph treatment improved survival rate and alleviated pulmonary pathological damage of the sepsis mice, as well as reduced the excessive release of pro-inflammatory cytokines IL-1ß, IL-18, IL-6, iNOS and chemokines MCP-1 regulated by MAPK/NF-κB pathway in pulmonary injury. Daph treatment decreased Caspase-3 and Bax, increased Bcl-2, inhibited nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis in lung tissues of septic lung injury. Also, Daph treatment reduced the level of excessive inflammatory mediators, inhibited apoptosis and pyroptosis in MLE-12 cells. It is noteworthy that the protective effect of Daph on MLE-12 cells damage and death was assisted by the enhanced expression of CD38. CONCLUSIONS: Our results demonstrated that Daph offered a beneficial therapeutic effect for septic lung injury via the up-regulation of CD38 and inhibition of MAPK/NF-κB/NLRP3 pathway. Video Abstract.
Asunto(s)
Lesión Pulmonar , Sepsis , Umbeliferonas , Animales , Ratones , Lipopolisacáridos , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/tratamiento farmacológico , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sepsis/metabolismo , Umbeliferonas/farmacologíaRESUMEN
Using an extended Su-Schrieffer-Heeger model and a nonadiabatic dynamics method, we investigate the dynamics of bipolarons in coupled nondegenerate organic chains including the spin-orbit coupling and interchain coupling. By tracing the time-dependent evolution of the charges and spins in each chain, an obvious oscillating spin Hall effect (SHE) from the bipolaron transport is revealed. The results are compared with that from polaron-dominated transport. A reduction of amplitude and an increase of oscillating frequency are observed for the SHE from the bipolaron transport. The mechanism is attributed to the enhanced skew scattering off the larger transient deformations of the chains in the case of the bipolaron. Spectrum analysis by fast Fourier transform of the SHE signal demonstrates a distinct shift of two characteristic peaks to a higher onset frequency compared to the polaron transport. The charge-spin conversion efficiency is also compared, where a larger conversion efficiency is obtained from the bipolaron transport due to the lower saturated velocity. The effects of the strength of the electric field and the interactions are discussed. This work reveals the role of the bipolaron in organic SHE and provides a feasible way to achieve larger conversion efficiency by controlling the species of carriers with the concentration of the dopant.
RESUMEN
OBJECTIVES: Optical Coherence Tomograph (OCT) imaging technology can be used to examine, in vivo, the human ET. At present, it is impossible to achieve the OCT scanning vivo and ex vivo in the same individual human body, or study the consistency between OCT images and histological images of the eustachian tube nasopharyngeal region and adjacent structures. The aim of this study was to determine the consistency between OCT images and histological sections in vivo and ex vivo in miniature pigs. METHODS: OCT imaging was performed on five adult miniature pigs in vivo and ex vivo. The images of the eustachian tube OCT (ET-OCT), nasopharynx OCT (NP-OCT) and histological cross sections were further studied. RESULTS: All five miniature pigs achieved the OCT scan successfully, acquiring ET-OCT and NP-OCT images in vivo and ex vivo on both sides. The acquired ET OCT images closely matched the histological images, revealing details of the cartilage, submucosa, glands, and mucosa. The lower segment of the ET wall mucosa had an abundance of glands and submucosal tissues, with more low-signal areas appearing in the ex vivo images. The NP-OCT images of the nasopharynx matched the details of the mucosa and submucosal tissues. The ex-vivo OCT images showed thicker mucosa and more scattered slightly lower signal areas compared to the vivo OCT images. CONCLUSIONS: ET-OCT images and NP-OCT images matched the histological structure of eustachian tube nasopharyngeal region structures in miniature pigs both in vivo and ex vivo. OCT images may be sensitive to changes in edema and ischemia status. There is a great potential for morphological assessment of inflammation, edema, injure, mucus gland status.
Asunto(s)
Trompa Auditiva , Adulto , Porcinos , Humanos , Animales , Trompa Auditiva/diagnóstico por imagen , Porcinos Enanos , Tomografía de Coherencia Óptica/métodos , Inflamación , Nasofaringe/diagnóstico por imagenRESUMEN
Objective: The prevalence of antimicrobial resistance in Helicobacter pylori (HP) infection has increased globally. This study aimed to compare the efficacy of Biling Weitong granules (BLWTG) combined with quadruple therapy in patients with refractory HP infection who had previously failed eradication therapy. Methods: This single-center prospective study enrolled patients with two or more consecutive failed HP treatments. A total of 122 patients with previously failed HP treatment from our hospital were recruited as participants and randomly (1:1) allocated to two eradication groups: patients treated with bismuth-containing quadruple therapy (esomeprazole 40 mg, amoxicillin 1.0 g, bismuth potassium citrate 220 mg, and clarithromycin 500 mg, twice daily [EACB group]) for 14 days. And those treated with BLWTG (5 g three times daily) combined with the EACB group for 14 days (BLWTG+EACB group). The therapeutic effects of the two treatment programs were comprehensively evaluated. Results: The study group had a significantly higher improvement rate in symptoms (dull stomach pain, nausea, gastric distension, loss of appetite, and belching) compared to the control group (P < .05). Eight weeks after drug withdrawal, the eradication rates in the control and study groups were 49.18% and 73.77%, respectively. The levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α were significantly lower in both groups after treatment but were significantly lower in the study group than in the control group (P < .05). Conclusions: The combination of BLWTG and standard four-drug therapy had a high eradication rate and low recurrence rate in patients with refractory HP infection. Additionally, this combined therapy could regulate inflammatory reactions and reduce drug-related adverse reactions.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/etiología , Bismuto/farmacología , Bismuto/uso terapéutico , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Estudios Prospectivos , Quimioterapia Combinada , Resultado del Tratamiento , Amoxicilina/uso terapéutico , Amoxicilina/farmacologíaRESUMEN
Objectives: This study aimed to examine (1) the feasibility of the study procedures (i.e. recruitment, retention, attendance, and assessment completion rates), and (2) the effects of horticultural therapy (HT) on apathy, cognitive ability, quality of life, and functional capacity.Methods: This was a parallel-group, match-paired, randomized controlled trial. Thirty-two participants were allocated to either the experimental or the control group. Data were collected at baseline (T0), immediately postintervention (T1), and 3 months postintervention (T2). The Apathy Evaluation Scale-informant version (AES-I); Mini-Mental State Examination (MMSE); Quality of Life in Alzheimer's disease (QoL-AD) scale; Barthel index (BI) were used to measure apathy, cognitive ability, quality of life, and functional capacity, respectively.Results: The recruitment, retention, attendance and assessment completion rates were 22.7%, 87.5%, 100% and 100%, respectively. The between-group differences in AES-I (p = 0.007) and MMSE (p = 0.034) scores were statistically significant at T1. In the experimental group, the AES-I (p = 0.001), MMSE (p = 0.010), and QoL-AD (p = 0.017) scores were significantly different over time. In the post hoc pair-wise analysis, the AES-I scores of the experimental group observed at T1 were significantly lower than that at T0 (p = 0.032). In the control group, the MMSE scores (p = 0.001) were significantly different over time.Conclusion: HT is feasible for residents with dementia and apathy. The HT program effectively reduced apathy and promoted cognitive function, but its effects on quality of life and functional capacity were not observed.
Asunto(s)
Enfermedad de Alzheimer , Apatía , Demencia , Terapia Hortícola , Demencia/terapia , Humanos , Casas de Salud , Proyectos Piloto , Calidad de VidaRESUMEN
BACKGROUND: Cucumber green mottle mosaic virus (CGMMV) causes substantial global losses in cucurbit crops, especially watermelon. N6-methyladenosine (m6A) methylation in RNA is one of the most important post-transcriptional modification mechanisms in eukaryotes. It has been shown to have important regulatory functions in some model plants, but there has been no research regarding m6A modifications in watermelon. RESULTS: We measured the global m6A level in resistant watermelon after CGMMV infection using a colorimetric method. And the results found that the global m6A level significantly decreased in resistant watermelon after CGMMV infection. Specifically, m6A libraries were constructed for the resistant watermelon leaves collected 48 h after CGMMV infection and the whole-genome m6A-seq were carried out. Numerous m6A modified peaks were identified from CGMMV-infected and control (uninfected) samples. The modification distributions and motifs of these m6A peaks were highly conserved in watermelon transcripts but the modification was more abundant than in other reported crop plants. In early response to CGMMV infection, 422 differentially methylated genes (DMGs) were identified, most of which were hypomethylated, and probably associated with the increased expression of watermelon m6A demethylase gene ClALKBH4B. Gene Ontology (GO) analysis indicated quite a few DMGs were involved in RNA biology and stress responsive pathways. Combined with RNA-seq analysis, there was generally a negative correlation between m6A RNA methylation and transcript level in the watermelon transcriptome. Both the m6A methylation and transcript levels of 59 modified genes significantly changed in response to CGMMV infection and some were involved in plant immunity. CONCLUSIONS: Our study represents the first comprehensive characterization of m6A patterns in the watermelon transcriptome and helps to clarify the roles and regulatory mechanisms of m6A modification in watermelon in early responses to CGMMV.
Asunto(s)
Tobamovirus/genética , Transcriptoma/genética , Adenosina/análogos & derivados , Adenosina/genética , Adenosina/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Enfermedades de las Plantas/virología , RNA-SeqRESUMEN
Smartphones are increasingly becoming an efficient platform for solving indoor positioning problems. Fingerprint-based positioning methods are popular because of the wide deployment of wireless local area networks in indoor environments and the lack of model propagation paths. However, Wi-Fi fingerprint information is singular, and its positioning accuracy is typically 2-10 m; thus, it struggles to meet the requirements of high-precision indoor positioning. Therefore, this paper proposes a positioning algorithm that combines Wi-Fi fingerprints and visual information to generate fingerprints. The algorithm involves two steps: merged-fingerprint generation and fingerprint positioning. In the merged-fingerprint generation stage, the kernel principal component analysis feature of the Wi-Fi fingerprint and the local binary pattern features of the scene image are fused. In the fingerprint positioning stage, a light gradient boosting machine (LightGBM) is trained with mutually exclusive feature bundling and histogram optimization to obtain an accurate positioning model. The method is tested in an actual environment. The experimental results show that the positioning accuracy of the LightGBM method is 90% within a range of 1.53 m. Compared with the single-fingerprint positioning method, the accuracy is improved by more than 20%, and the performance is improved by more than 15% compared with other methods. The average locating error is 0.78 m.
RESUMEN
In recent years, people's daily lives have become inseparable from a variety of electronic devices, especially mobile phones, which have undoubtedly become necessity in people's daily lives. In this paper, we are looking for a reliable way to acquire visual quality of the display product so that we can improve the user's experience with the display product. This paper proposes two major contributions: the first one is the establishment of a new subjective assessment database (DPQAD) of display products' screen images. Specifically, we invited 57 inexperienced observers to rate 150 screen images showing the display product. At the same time, in order to improve the reliability of screen display quality score, we combined the single stimulation method with the stimulation comparison method to evaluate the newly created display products' screen images database effectively. The second one is the development of a new no-reference image quality assessment (IQA) metric. For a given image of the display product, first our method extracts 27 features by analyzing the contrast, sharpness, brightness, etc., and then uses the regression module to obtain the visual quality score. Comprehensive experiments show that our method can evaluate natural scene images and screen content images at the same time. Moreover, compared with ten state-of-the-art IQA methods, our method shows obvious superiority on DPQAD.
RESUMEN
Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) play vital roles in plant defense responses against viral infections. However, there is no systematic understanding of lncRNAs and circRNAs and their competing endogenous RNA (ceRNA) networks in watermelon under cucumber green mottle mosaic virus (CGMMV) stress. Here, we present the characterization and expression profiles of lncRNAs and circRNAs in watermelon leaves 48-h post-inoculation (48 hpi) with CGMMV, with mock inoculation as a control. Deep sequencing analysis revealed 2373 lncRNAs and 606 circRNAs in the two libraries. Among them, 67 lncRNAs (40 upregulated and 27 downregulated) and 548 circRNAs (277 upregulated and 271 downregulated) were differentially expressed (DE) in the 48 hpi library compared with the control library. Furthermore, 263 cis-acting matched lncRNA-mRNA pairs were detected for 49 of the DE-lncRNAs. KEGG pathway analysis of the cis target genes of the DE-lncRNAs revealed significant associations with phenylalanine metabolism, the citrate cycle (TCA cycle), and endocytosis. Additionally, 30 DE-lncRNAs were identified as putative target mimics of 33 microRNAs (miRNAs), and 153 DE-circRNAs were identified as putative target mimics of 88 miRNAs. Furthermore, ceRNA networks of lncRNA/circRNA-miRNA-mRNA in response to CGMMV infection are described, with 12 DE-lncRNAs and 65 DE-circRNAs combining with 22 miRNAs and competing for the miRNA binding sites on 29 mRNAs. The qRT-PCR validation of selected lncRNAs and circRNAs showed a general correlation with the high-throughput sequencing results. This study provides a valuable resource of lncRNAs and circRNAs involved in the response to CGMMV infection in watermelon.
Asunto(s)
Citrullus/virología , Interacciones Huésped-Patógeno , Enfermedades de las Plantas/virología , ARN Circular/metabolismo , ARN Largo no Codificante/metabolismo , ARN de Planta/metabolismo , Tobamovirus/crecimiento & desarrollo , Citrullus/inmunología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedades de las Plantas/inmunología , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
An N-heterocyclic carbene (NHC)-catalyzed α-functionalization of the in situ activated α,ß-unsaturated carboxylic acids bearing γ-H was realized through formal [4 + 2] annulations with o-quinone methides, which paved a new avenue for the assembly and modification of the dihydrocoumarin scaffold in good yields with excellent diastereo- and enantioselectivities.
RESUMEN
Randomized controlled trials (RCTs) are important for evidence-based medicine; however, their quality of reporting remains to be evaluated. The aim of this study was to assess the quality of the report concerning solid tumor medication. Articles were searched in PubMed to identify all oncology phase III RCTs published from 2011 to 2015, and the results were classified manually through Endnote X7.0 software. Registration rate, primary end point (PEP) consistency, positive result rate, enrollment time point, outcome feedback in the registry, and publish time zone were extracted and assessed. The overall registration rate was higher than years before; nevertheless, a portion of trials showed PEP discrepancies and enrolled patients before registration in either journal formats. Trials published in top 5 general medical journals paid more attention to results feedback on registration websites and were more prompt with publication after study accomplishment. Our data suggested general medical journals may be more rigorous compared to oncology journals but identified a preference for positive results. On the whole, RCTs published between 2011 and 2015 seemed fairly standardized. Surveillance in registry and outcome feedback still needs to be strengthened for the stringency and reliability of clinical trials in solid tumor medication territory.
Asunto(s)
Antineoplásicos/uso terapéutico , Exactitud de los Datos , Neoplasias/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Informe de Investigación/normas , Medicina Basada en la Evidencia/normas , Humanos , Oncología Médica/normas , Reproducibilidad de los ResultadosRESUMEN
Dysferlinopathy, a progressive muscular dystrophy, results from mutations in the Dysferlin gene (DYSF, MIM*603009). Traditional diagnosis relies on the reduction or absence of dysferlin. However, altered dysferlin has been observed in other myopathies, leading to a precise diagnosis through molecular genetics. In this study, we report a patient who was previously misdiagnosed as inflammatory myopathy based on routine clinicopathological examinations alone. However, muscle biopsy specimens were analyzed further by immunohistochemistry of muscular dystrophy-related proteins, and gene-targeted next generation sequencing (NGS) was used to correctly identify muscular dystrophy. DNA was sequenced with NGS and the detected mutation was verified by Sanger sequencing. Our targeted NGS found a novel missense mutation (c.5392G > A) in the DYSF gene, allowing correct diagnosis of LGMD2B in our patient. We discovered of a novel missense mutation in the DYSF gene and have broadened the DYSF mutation spectrum, which may be correlated in patients with presumed dysferlinopathy, especially when lymphocytic infiltration is observed.
RESUMEN
Stochastic resonance is studied in a class of non-smooth systems with a controllable parameter causing a change among monostability, bistability, and multistability, driven by colored noise. The system becomes smooth at a bifurcation point. Time scales in the non-smooth well are analyzed and transition rates of the non-smooth potential barriers are obtained. Analytical expressions for the response amplitude depending on the controllable parameter, frequency, noise intensity, and correlation time are derived in the bistable and multistable regions in the adiabatic limit. With the decrease of frequency, the optimal correlation time according to the maximum response is increasing; on the contrary, the optimal noise intensity is on the decline. Multistability of the system enhances the optimal transition rates and optimal response amplitude.
RESUMEN
Context 2a,-3a,-24-Trihydroxyurs-12-en-28-oic acid (TEO, a corosolic acid analogue) is a triterpenoid saponin isolated from Actinidia valvata Dunn (Actinidiaceae), a well-known traditional Chinese medicine. Objective This study investigated the anti-proliferation and inducing apoptosis effects of TEO in three human hepatocellular carcinoma (HCC) cell lines. Materials and methods Cytotoxic activity of TEO was determined by the MTT assay at various concentrations from 2.5 to 40 µg/mL in BEL-7402, BEL-7404 and SMMC-7721 cell lines. Cell morphology was assessed by acridine orange/ethidium bromide and 4'-6-diamidino-2-phenylindole dihydrochloride staining and fluorescence microscopy. Cell-cycle distribution and DNA damage were determined by flow cytometry and comet assay. Mitochondrial dysfunction was assessed by JC-1 staining and transmission electron microscopy. Apoptosis changes were explored by Western blot, TNF-α and caspase-3, -8, -9 assays. Results TEO exhibited inhibition effects on BEL-7402, BEL-7404 and SMMC-7721 cells treated for 24 h, the IC50 values were 34.6, 30.8 and 30.5 µg/mL, respectively. TEO (40 µg/mL)-treated three cell lines increased by more than 21% in the G1 phase and presented the morphological change and DNA damage. TEO also declined the mitochondrial membrane potential and altered mitochondrial ultra-structure. Furthermore, caspase-3, caspase-8, caspase-9 and TNF-α were also activated. Mechanism investigation showed that TEO could decrease anti-apoptotic Bcl-2 protein expression, increase proapoptotic Bax and Bid proteins expressions and increase Bax/Bcl-2 ratio. Conclusion Our results demonstrate for the first time that TEO inhibited growth of HCC cell lines and induced G1 phase arrest. Moreover, proapoptotic effects of TEO were mediated through the activation of TNF-α, caspases and mitochondrial pathway.
Asunto(s)
Actinidia , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Mitocondrias Hepáticas/efectos de los fármacos , Extractos Vegetales/farmacología , Triterpenos/farmacología , Actinidia/química , Proteínas Reguladoras de la Apoptosis/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/ultraestructura , Línea Celular Tumoral , Forma de la Célula/efectos de los fármacos , Daño del ADN , Relación Dosis-Respuesta a Droga , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/ultraestructura , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Mitocondrias Hepáticas/ultraestructura , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Triterpenos/aislamiento & purificación , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Maternal immune tolerance to the semi-allogenic fetus is required for successful pregnancy in mammals. Monoclonal nonspecific suppressor factor beta (MNSFB) is an immunosuppressive factor present in uterine epithelial and stromal cells, as well as in macrophages and T cells. Although the functional neutralization of MNSFB using specific antibodies against it lead to failed embryo implantation in mice, the exact role of MNSFB at the fetal-maternal interface remains unclear. The present study generated conditional heterozygous Mnsfb-deficient (Mnsfb(+/) (-) ) mice using the LoxP/Cre system. Western-blot analyses showed that uterine MNSFB protein in Mnsfb(+/-) mice was remarkably down-regulated compared to that in the wild-type (Mnsfb(+/+) ) mice. The litter size of female Mnsfb(+/-) mice was significantly reduced, which corresponded to developmental failure of embryos beyond Day 11 of pregnancy. The expression level of MNSFB protein was also lower in the failing compared to the normal embryos. An aberrant interaction between the embryos of Day-4 pregnant wild-type mice and endometrial stromal cells of female Mnsfb(+/-) mice was observed in vitro. The uterine Day-5 abundance of P53, BAX, and BCL-G in pregnant Mnsfb(+/-) mice was significantly decreased compared to that of wild-type mice, whereas the expression of P27 and tumor necrosis factor alpha (TNFA) was elevated. By comparison, the levels of MNSFB and BAX proteins in human decidual tissues obtained from recurrent spontaneous miscarriage patients were significantly reduced compared to those obtained from legal medial abortion, highlighting the involvement of MNSFB in the pathogenesis of recurrent spontaneous miscarriage. Together, these results demonstrated that a deficiency in MNSFb is associated with pregnancy loss, probably through reduced P53 and/or increased TNFA production at the fetal-maternal interface.