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The intestinal barrier is vulnerable to damage by microbiota-induced inflammation that is normally restrained through mechanisms promoting homeostasis. Such disruptions contribute to autoimmune and inflammatory diseases including inflammatory bowel disease. We identified a regulatory loop whereby, in the presence of the normal microbiota, intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CX3CR1 reduced expansion of intestinal microbe-specific T helper 1 (Th1) cells and promoted generation of regulatory T cells responsive to food antigens and the microbiota itself. We identified that disruption of the microbiota resulted in CX3CR1+ APC-dependent inflammatory Th1 cell responses with increased pathology after pathogen infection. Colonization with microbes that can adhere to the epithelium was able to compensate for intestinal microbiota loss, indicating that although microbial interactions with the epithelium can be pathogenic, they can also activate homeostatic regulatory mechanisms. Our results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes tissue homeostasis.
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Receptor 1 de Quimiocinas CX3C/metabolismo , Microbioma Gastrointestinal/inmunología , Mucosa Intestinal/inmunología , Sistema Mononuclear Fagocítico/inmunología , Linfocitos T Reguladores/inmunología , Células TH1/inmunología , Animales , Presentación de Antígeno , Adhesión Bacteriana/inmunología , Modelos Animales de Enfermedad , Femenino , Homeostasis , Tolerancia Inmunológica , Inmunidad Mucosa , Inflamación/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Interleucina-10/inmunología , Interleucina-10/metabolismo , Mucosa Intestinal/microbiología , Masculino , Ratones , Células RAW 264.7RESUMEN
Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection1. Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen while limiting inflammatory anti-commensal responses1,2. Antigen-specific recognition of intestinal microorganisms by T cells has previously been described3,4. Although the local environment shapes the differentiation of effector cells3-5 it is unclear how microbiota-specific T cells are educated in the thymus. Here we show that intestinal colonization in early life leads to the trafficking of microbial antigens from the intestine to the thymus by intestinal dendritic cells, which then induce the expansion of microbiota-specific T cells. Once in the periphery, microbiota-specific T cells have pathogenic potential or can protect against related pathogens. In this way, the developing microbiota shapes and expands the thymic and peripheral T cell repertoire, allowing for enhanced recognition of intestinal microorganisms and pathogens.
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Células Dendríticas/inmunología , Microbioma Gastrointestinal/inmunología , Linfocitos T/citología , Linfocitos T/inmunología , Timo/citología , Timo/inmunología , Envejecimiento/inmunología , Animales , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/metabolismo , Receptor 1 de Quimiocinas CX3C/metabolismo , ADN Bacteriano/análisis , Células Dendríticas/metabolismo , Escherichia coli/inmunología , Femenino , Masculino , Ratones , Especificidad de Órganos , Salmonella/inmunología , Simbiosis/inmunología , Timo/metabolismoRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Phosphorylation and dephosphorylation of viral movement proteins plays a crucial role in regulating virus movement. Our study focused on investigating the movement protein TGBp1 of Bamboo mosaic virus (BaMV), which is a single-stranded positive-sense RNA virus. Specifically, we examined four potential phosphorylation sites (S15, S18, T58, and S247) within the TGBp1 protein. To study the impact of phosphorylation, we introduced amino acid substitutions at the selected sites. Alanine substitutions were used to prevent phosphorylation, while aspartate substitutions were employed to mimic phosphorylation. Our findings suggest that mimicking phosphorylation at S15, S18 and T58 of TGBp1 might be linked to silencing suppressor activities. The phosphorylated form at these sites exhibits a loss of silencing suppressor activity, leading to reduced viral accumulation in the inoculated leaves. Furthermore, mimicking phosphorylation at residues S15 and S18 could diminish viral accumulation at the single-cell level, while doing so at residue T58 could influence virus movement. However, mimicking phosphorylation at residue S247 does not appear to be relevant to both functions of TGBp1. Overall, our study provides insights into the functional significance of specific phosphorylation sites in BaMV TGBp1, illuminating the regulatory mechanisms involved in virus movement and silencing suppression.
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Potexvirus , Fosforilación , Potexvirus/genética , Alanina , Sustitución de AminoácidosRESUMEN
Persistent organic pollutants (POPs), including xenoestrogens and polyfluoroalkyl substances (PFAS), demand urgent global intervention. Fenton oxidation, catalyzed by iron ions, offers a cost-effective means to degrade POPs. However, numerous challenges like acid dependency, catalyst loss, and toxic waste generation hinder practical application. Efforts to create long-lasting heterogeneous Fenton catalysts, capable of simultaneously eliminating acid requirements, sustaining rapid kinetics, and retaining iron efficiently, have been unsuccessful. This study introduces an innovative heterogeneous zwitterionic hydrogel-based Fenton catalyst, surmounting these challenges in a cost-effective and scalable manner. The hydrogel, hosting individually complexed iron ions in a porous scaffold, exhibits substantial effective surface area and kinetics akin to homogeneous Fenton reactions. Complexed ions within the hydrogel can initiate Fenton degradation at neutral pH, eliminating acid additions. Simultaneously, the zwitterionic hydrogel scaffold, chosen for its resistance to Fenton oxidation, forms strong bonds with iron ions, enabling prolonged reuse. Diverging from existing designs, the catalyst proves compatible with UV-Fenton processes and achieves rapid self-regeneration during operation, offering a promising solution for the efficient and scalable degradation of POPs. The study underscores the efficacy of the approach by demonstrating the swift degradation of three significant contaminants-xenoestrogens, pesticides, and PFAS-across multiple cycles at trace concentrations.
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Interstitial cystitis/bladder pain syndrome with Hunner's lesion (HIC) is characterized by chronic inflammation and nerve hyperplasia; however, the pathogenesis of HIC remains a mystery. In this study, we detected both Epstein-Barr virus (EBV) latency infection genes EBNA-1 and LMP-1 and EBV lytic infection BZLF-1 and BRLF-1 expression in the HIC bladders, indicating the coexistence of EBV persistence and reactivation in the B cells in HIC bladders. Upregulation of EBV-associated inflammatory genes in HIC bladders, such as TNF-α and IL-6, suggests EBV infection is implicated in the pathogenesis of bladder inflammation. Nerve hyperplasia and upregulation of brain-derived neurotrophic factor (BDNF) were noted in the HIC bladders. Double immunochemical staining and flow cytometry revealed the origin of BDNF to be EBV-infected B cells. Inducible BDNF expression was noted in B cells upon EBV infection, but not in the T cells. A chromatin immunoprecipitation study revealed BDNF transcription could be promoted by cooperation between EBV nuclear antigens, chromatin modifiers, and B-cell-specific transcription. Knockdown of BDNF in EBV-infected B cells resulted in the inhibition of cell proliferation and viability. Downregulation of phosphorylated SMAD2 and STAT3 after BDNF knockdown may play a role in the mechanism. Implantation of latent EBV-infected B cells into rat bladder walls resulted in a higher expression level of CD45 and PGP9.5, suggesting tissue inflammation and nerve hyperplasia. In contrast, implantation of BDNF depleted EBV-infected B cells abrogated these effects. This is the first study to provide insights into the mechanisms underlying the involvement of EBV-infected B cells in HIC pathogenesis. © 2022 The Pathological Society of Great Britain and Ireland.
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Cistitis Intersticial , Cistitis , Infecciones por Virus de Epstein-Barr , Animales , Ratas , Cistitis Intersticial/genética , Cistitis Intersticial/complicaciones , Cistitis Intersticial/metabolismo , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Hiperplasia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Cistitis/complicaciones , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Proteínas Virales/metabolismo , Inflamación/complicacionesRESUMEN
Knockout of ERß in the mouse leads to nuclear expression of epidermal growth factor receptor (EGFR) in the prostate. To examine whether ERß plays a similar role in the human prostate, we used four cohorts of men: 1) a Swedish cohort of normal prostates and PCa (prostate cancer) of different Gleason grades; 2) men with benign prostatic hyperplasia (BPH) treated with the 5α-reductase inhibitor, finasteride, and finasteride together with the ERß agonists, soy isoflavones; 3) men with PCa above Gleason grade 4 (GG4), treated with ADT (androgen deprivation therapy) and abiraterone (AA), the blocker of androgen synthesis for different durations; and 4) men with GG4 PCa on ADT or ADT with the AR (androgen receptor) blocker, enzalutamide, for 4 mo to 6 mo. In men with BPH, finasteride treatment induced EGFR nuclear expression, but, when finasteride was combined with isoflavones, EGFR remained on the cell membrane. In GG4 patients, blocking of AR for 4 mo to 6 mo resulted in loss of ERß and PTEN expression and increase in patients with nuclear EGFR from 10 to 40%. In the men with GG4 PCa, blocking of adrenal synthesis of testosterone for 2 mo to 7 mo had the beneficial effect of increasing ERß expression, but, on treatment longer than 8 mo, ERß was lost and EGFR moved to the nucleus. Since nuclear EGFR is a predictor of poor outcome in PCa, addition of ERß agonists together with abiraterone should be considered as a treatment that might sustain expression of ERß and offer some benefit to patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Receptor beta de Estrógeno/agonistas , Hiperplasia Prostática/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Transporte Activo de Núcleo Celular/efectos de los fármacos , Antagonistas de Andrógenos/farmacología , Antagonistas de Andrógenos/uso terapéutico , Androstenos/farmacología , Androstenos/uso terapéutico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzamidas/farmacología , Benzamidas/uso terapéutico , Biopsia , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Estudios de Cohortes , Receptores ErbB/metabolismo , Receptor beta de Estrógeno/metabolismo , Finasterida/farmacología , Finasterida/uso terapéutico , Humanos , Masculino , Ratones , Ratones Noqueados , Clasificación del Tumor , Nitrilos/farmacología , Nitrilos/uso terapéutico , Fosfohidrolasa PTEN/metabolismo , Feniltiohidantoína/farmacología , Feniltiohidantoína/uso terapéutico , Fitoestrógenos/farmacología , Fitoestrógenos/uso terapéutico , Próstata/citología , Próstata/efectos de los fármacos , Próstata/patología , Hiperplasia Prostática/patología , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismoRESUMEN
BACKGROUND: The status of central lymph nodes is crucial for determining the surgical approach to papillary thyroid carcinoma (PTC). Because of the differences between genders in central lymph node metastasis (CLNM), we aimed to construct separate predictive models for CLNM according to gender. METHODS: In our study, a total of 1258 PTC patients who underwent thyroid cancer surgery from September 2021 to March 2023 were analyzed retrospectively. The data were analysed univariately and multivariately using SPSS software grouped according to gender and nomograms of CLNM were plotted using R software. The variables included in this study were sex, Age, body mass index, Diabetes, chronic lymphocytic thyroiditis (CLT), Suspicious central lymph node (SCLN), A/T, Margin, Microcalcification (MC), BRAF, Number, Location, CLNM. RESULTS: The preoperative nomogram in male patients included four clinical variables: CLT, Margin, Number, Size. The preoperative nomogram of female patients included six clinical variables: Age, SCLN, Margin, MC, Number, Size. The calibration curves showed great agreement in both the training group and the validation group. The decision curve analysis showed the feasibility of nomogram in predicting CLNM in both man and woman. CONCLUSION: Based on the successful establishment of nomogram, we can analyze the variability of CLNM between male and female, which may provide clinicians with personalized clinical schemes in the treatment of PTC.
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Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Masculino , Femenino , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Nomogramas , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Estudios Retrospectivos , Metástasis Linfática/patología , Carcinoma Papilar/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Factores de RiesgoRESUMEN
OBJECTIVE: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia. MATERIALS AND METHODS: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1ß, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model. RESULTS: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model. CONCLUSIONS: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.
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Flavonas , Microglía , Factor 88 de Diferenciación Mieloide , Factor de Transcripción STAT3 , Receptor Toll-Like 4 , Pez Cebra , Animales , Receptor Toll-Like 4/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Factor de Transcripción STAT3/metabolismo , Ratones , Flavonas/farmacología , Factor 88 de Diferenciación Mieloide/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Lipopolisacáridos/toxicidad , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Línea Celular , Antiinflamatorios/farmacologíaRESUMEN
Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan. Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.
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Hiperaldosteronismo , Hipertensión , Humanos , Aldosterona , Hiperaldosteronismo/diagnóstico , Renina , Hidrocortisona , CaptoprilRESUMEN
Adrenal venous sampling (AVS) is a crucial method for the lateralization of primary aldosteronism (PA). It is advised to halt the use of the patient's antihypertensive medications and correct hypokalemia prior to undergoing AVS. Hospitals equipped to conduct AVS should establish their own diagnostic criteria based on current guidelines. If the patient's antihypertensive medications cannot be discontinued, AVS can be performed as long as the serum renin level is suppressed. The Task Force of Taiwan PA recommends using a combination of adrenocorticotropic hormone stimulation, quick cortisol assay, and C-arm cone-beam computed tomography to maximize the success of AVS and minimize errors by using the simultaneous sampling technique. If AVS is not successful, an NP-59 (131 I-6-ß-iodomethyl-19-norcholesterol) scan can be used as an alternative method to lateralize PA. We depicted the details of the lateralization procedures (mainly AVS, and alternatively NP-59) and their tips and tricks for confirmed PA patients who would consider to undergo surgical treatment (unilateral adrenalectomy) if the subtyping shows unilateral disease.
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Glándulas Suprarrenales , Hiperaldosteronismo , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Aldosterona , Antihipertensivos , Adosterol , Estudios RetrospectivosRESUMEN
The implantation of human embryos is a complex process involving various cytokines and receptors expressed by both endometrium and embryos. However, the role of cytokines produced by a single embryo in successful implantation is largely unknown. This study aimed to investigate the role of IL-1ß expressed in a single-embryo-conditioned medium (ECM) in embryo implantation. Seventy samples of single ECM were analyzed by a specially designed magnetic-beads-based microfluidic chip from 15 women. We discovered that IL-1ß level increased as the embryo developed, and the difference was significant. In addition, receiver operator characteristic (ROC) curves analysis showed a higher chance of pregnancy when the IL-1ß level on day 5 ECM was below 79.37 pg/mL and the difference between day 5 and day 3 was below 24.90 pg/mL. Our study discovered a possible association between embryonic proteomic expression and successful implantation, which might facilitate single-embryo transfer in the future by helping clinicians identify the embryo with the greatest implantation potential.
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Microfluídica , Proteómica , Embarazo , Humanos , Femenino , Medios de Cultivo Condicionados , Interleucina-1beta , Blastocisto , Implantación del Embrión , CitocinasRESUMEN
BACKGROUND: Establishing a nurturing bond with the unborn child is essential for expectant mothers throughout pregnancy. While the influence of family support and pregnancy adaptation on maternal-fetal bonding is evident, these factors remain unexplored in the early stages of pregnancy. This study aims to elucidate the dynamic interaction between family support, pregnancy adaptation, and maternal-fetal bonding during the first trimester, explicitly investigating the mediating role of pregnancy adaptation. METHOD: A cross-sectional design was conducted to recruit expectant mothers between 8 and 12 weeks of gestation without significant complications. RESULTS: Family support and pregnancy adaptation emerged as significant predictors of maternal-fetal bonding, and pregnancy adaptation mediated the relationship between family support and maternal-fetal bonding in the first trimester. CONCLUSIONS: The study confirms the critical role of family support and pregnancy adaptation in facilitating maternal-fetal bonding during early pregnancy, with pregnancy adaptation fully mediating this relationship. Healthcare providers are encouraged to involve family members in early interventions, focusing on assessing family support and engaging them in education and activities to strengthen the emotional bond between the mother and her unborn child.
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Duchenne muscular dystrophy (DMD), the most common form of childhood muscular dystrophy, is caused by mutations in the dystrophin gene. In addition to debilitating muscle degeneration, patients display a range of cognitive deficits thought to result from the loss of dystrophin normally expressed in the brain. While the function of dystrophin in muscle tissue is well characterized, its role in the brain is still poorly understood. The highest expression of dystrophin in the mouse brain is in cerebellar Purkinje cells (PCs), where it colocalizes with GABAA receptor clusters. Using ex vivo electrophysiological recordings from connected molecular layer interneuron (MLI)-PC pairs, we investigated changes in inhibitory synaptic transmission caused by dystrophin deficiency. In male mdx mice (which lack long-form dystrophin), we found that responses at MLI-PC pairs were reduced by â¼60% because of both decreased quantal response amplitude and a reduced number of functional vesicle release sites. Using electron microscopy, we found significantly fewer and smaller anatomically defined inhibitory synapses contacting the soma of PCs in mdx mice, suggesting that dystrophin may play a critical role in synapse formation and/or maintenance. Functionally, we found reduced MLI-evoked pauses in PC firing in acute slices. In vivo recordings from awake mdx mice showed increased sensory-evoked simple spike firing in positively modulating PCs, consistent with reduced feedforward inhibition, but no change in negatively modulating PCs. These data suggest that dystrophin deficiency in PCs disrupts inhibitory signaling in the cerebellar circuit and PC firing patterns, potentially contributing to cognitive and motor deficits observed in mdx mice and DMD patients.SIGNIFICANCE STATEMENT Duchenne muscular dystrophy (DMD) is primarily characterized by progressive muscle weakening caused by genetic mutations in the gene for dystrophin. Dystrophin is also normally expressed in the CNS, and DMD patients experience a range of nonprogressive cognitive deficits. The pathophysiology of CNS neurons resulting from loss of dystrophin and the function of dystrophin in neurons are still poorly understood. Using cerebellar PCs as a model, we found that the loss of dystrophin specifically disrupts the number and strength of inhibitory synaptic connections, suggesting that dystrophin participates in formation and/or maintenance of these synapses. This work provides insight into the function of dystrophin in the CNS and establishes neuronal and synaptic dysfunction, which may underlie cognitive deficits in DMD.
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Distrofia Muscular de Duchenne , Células de Purkinje , Animales , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Endogámicos mdx , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patología , Células de Purkinje/metabolismo , Células de Purkinje/patología , Receptores de GABA-A/metabolismo , Transmisión Sináptica/fisiologíaRESUMEN
BACKGROUND: Recent years have witnessed impressive growth in applying natural medicine in tumor treatment. Saffron is reported to elicit an inhibitory property against BC. Herein, we sought to explore the specific components and mechanistic basis of saffron's anti-breast carcinoma (BC) function. METHODS: Bioinformatics analysis was employed to analyze saffron components' anti-BC activity and screen the corresponding target genes involved in BC. Then, the roles of the main saffron ingredient quercetin in the activity of BC cells were examined using CCK-8, MTS, flow cytometry, colony formation, Transwell, and Gelatin zymogram assays. Additionally, the interactions among Quercetin, EET, and Stat3 were assessed by immunofluorescence and Western blot, and LC-MS/MS determined the levels of AA, EETs, and CYP3A. Finally, BC xenograft mouse models were established to verify the anti-BC function of Quercetin in vivo. RESULTS: Quercetin, the main active component of saffron, inhibited BC progression. Quercetin suppressed BC cell growth, migration, and invasion and inhibited CYP3A4 expression and activity in BC. Mechanistically, Quercetin down-regulated CYP3A4 to block the nuclear translocation of Stat3 by decreasing the metabolization of AA to EETs, thereby alleviating BC. Moreover, exogenously added EETs counteracted the anti-tumor effect of Quercetin on BC. Quercetin also inhibited the tumor growth of tumor-bearing nude mice. CONCLUSION: Quercetin could inhibit the activity of CYP3A to down-regulate AA metabolites EETs, consequently hampering p-Stat3 and nuclear translocation, thus impeding BC development.
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Productos Biológicos , Neoplasias de la Mama , Humanos , Animales , Ratones , Femenino , Ácido Araquidónico , Citocromo P-450 CYP3A , Quercetina/farmacología , Quercetina/uso terapéutico , Cromatografía Liquida , Ratones Desnudos , Espectrometría de Masas en Tándem , Neoplasias de la Mama/tratamiento farmacológicoRESUMEN
The full spectrum of risks for the life course of inactive hepatitis B virus (HBV) carriers remains unclear. In this study, 995 untreated HBV carriers (median age: 42.8 years; median follow-up: 30.2 years) were included. Their data were sourced from a population-based cohort study of male civil servants recruited in 1989-1992. Outcomes were identified by active follow-up examinations and linkage with national health insurance research database. At baseline, 483 subjects were inactive carriers, 385 with indeterminate phase, and 127 with other phases. The joint lifetime risk for incident cirrhosis, decompensation, hepatocellular carcinoma, and liver-related deaths was lower for inactive carriers compared to subjects in other phases (p < 0.0001). There was a trend of increase in incidence among inactive carriers; the 5-, 10-, and 20-year cumulative incidences were 1.86%, 6.03%, and 10.07%, respectively. Of the inactive carriers, 37.7% cleared HBsAg and 36.6% had biochemical relapse during the study. Biochemical relapse, obesity, and advanced age were predictors for disease progression in inactive carriers. Virological relapse was the predominant cause of biochemical relapse. Higher HBV-DNA levels (≥1000 copies/mL or 200 IU/mL) and HBV genotype B (vs. C) were associated with higher virological relapse rate. After 30 years, we found that one-time measure of inactive carrier state continued to have the lowest risk compared with other infection phases. Despite a more favorable prognosis, inactive carriers had a non-negligible risk. Our findings of lifetime risk may provide important clues for the management of such patients and consideration of therapeutic strategies aiming to achieve functional cure.
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Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , Humanos , Masculino , Adulto , Estudios de Cohortes , Recurrencia Local de Neoplasia , Virus de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B , ADN Viral/genética , Neoplasias Hepáticas/epidemiología , Recurrencia , Antígenos e de la Hepatitis B , Portador Sano/epidemiología , Hepatitis B/complicacionesRESUMEN
Atomic layer deposited Al2O3 films are incorporated into miniature light emitting diodes (mini-LEDs) as an internal moisture barrier layer. The experimental results show that the water vapor transmission rate reaches ≤10-4â g/m2/day when the Al2O3 thickness is ≥40â nm. The mini-LED with a 40â nm-thick Al2O3 layer shows negligible degradation after 1000â h of 85°C/85% relative humidity testing, whereas the device without an Al2O3 layer fails after only 500â h due to delamination occurring at the GaN surface. Current-voltage characteristics of the device without an Al2O3 moisture barrier layer indicate an increase in series resistance and ideality factor. This study provides a simple, light-weighting method to have a satisfactory encapsulation function for miniature LEDs.
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Constituting approximately 10% of flowering plant species, orchids (Orchidaceae) display unique flower morphologies, possess an extraordinary diversity in lifestyle, and have successfully colonized almost every habitat on Earth. Here we report the draft genome sequence of Apostasia shenzhenica, a representative of one of two genera that form a sister lineage to the rest of the Orchidaceae, providing a reference for inferring the genome content and structure of the most recent common ancestor of all extant orchids and improving our understanding of their origins and evolution. In addition, we present transcriptome data for representatives of Vanilloideae, Cypripedioideae and Orchidoideae, and novel third-generation genome data for two species of Epidendroideae, covering all five orchid subfamilies. A. shenzhenica shows clear evidence of a whole-genome duplication, which is shared by all orchids and occurred shortly before their divergence. Comparisons between A. shenzhenica and other orchids and angiosperms also permitted the reconstruction of an ancestral orchid gene toolkit. We identify new gene families, gene family expansions and contractions, and changes within MADS-box gene classes, which control a diverse suite of developmental processes, during orchid evolution. This study sheds new light on the genetic mechanisms underpinning key orchid innovations, including the development of the labellum and gynostemium, pollinia, and seeds without endosperm, as well as the evolution of epiphytism; reveals relationships between the Orchidaceae subfamilies; and helps clarify the evolutionary history of orchids within the angiosperms.
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Evolución Molecular , Genoma de Planta/genética , Orchidaceae/genética , Filogenia , Genes de Plantas/genética , Orchidaceae/anatomía & histología , Orchidaceae/clasificación , TranscriptomaRESUMEN
OBJECTIVE: Patients with Graves' disease who remain hyperthyroid under the treatment of antithyroid drugs (ATD) or cannot tolerate ATD usually receive radioactive iodine (RAI) to control disease activity. This pilot study aimed to identify predictors of prolonged euthyroidism > 12 months after receiving RAI. METHODS: Demographic, clinical, and laboratory data from 117 patients receiving RAI were retrospectively collected, including age, gender, body surface area, smoking status, free thyroxine, thyrotropin, thyrotropin binding inhibiting immunoglobulin, microsomal antibody, thyroglobulin antibody, medication history, and thyroid volume. Only 85 patients without missing values were included in statistical analysis. The calculated RAI dose was the estimated thyroid volume × 0.4. The difference and ratio between the actual and calculated RAI doses were examined. A stepwise logistic regression analysis was conducted to identify important predictors of prolonged euthyroidism > 12 months. The cut-off values for discretizing continuous covariates were estimated by fitting generalized additive models. RESULTS: Among the 85 patients on RAI, 18 (21.2%) achieved prolonged euthyroidism > 12 months, 38 (44.7%) remained hyperthyroid with decreased ATD doses, but 29 (34.1%) suffered permanent hypothyroidism and needed long-term levothyroxine. Logistic regression analysis revealed that patients with age > 66 years, 33 < age ≤ 66 years, quitting smoking vs nonsmoking or current smoking, 600 < micorsomal antibody ≤ 1729 IU/mL, 47% < thyrotropin binding inhibiting immunoglobulin ≤ 81%, 7 < thyroglobulin antibody ≤ 162 IU/mL, 0.63 < ratio between actual and calculated RAI doses ≤ 1.96, or taking hydroxychloroquine would have a higher chance of reaching prolonged euthyroidism > 12 months after receiving RAI. Its area under the Receiver Operating Characteristic (ROC) curve was 0.932. CONCLUSION: Patients with Graves' disease who received an actual RAI dose close to the calculated RAI dose achieved prolonged euthyroidism > 12 months if they also took hydroxychloroquine during RAI treatment.
Asunto(s)
Enfermedad de Graves , Hipertiroidismo , Yodo , Neoplasias de la Tiroides , Humanos , Preescolar , Radioisótopos de Yodo/uso terapéutico , Proyectos Piloto , Tiroglobulina , Estudios Retrospectivos , Hidroxicloroquina/uso terapéutico , Enfermedad de Graves/tratamiento farmacológico , Enfermedad de Graves/radioterapia , Hipertiroidismo/tratamiento farmacológico , Antitiroideos/uso terapéutico , TirotropinaRESUMEN
BACKGROUND: Creating a supportive breastfeeding environment after childbirth and enabling women to work with reassurance are essential in maternal care services. The study aimed to explore the effectiveness of the utilization rate of public and workplace lactation rooms in relation to the breastfeeding rate among postpartum women returning to work in Taiwan. METHODS: The study involved a secondary data analysis on 6,992 and 7,350 postpartum women surveyed in 2011 and 2016, respectively. Interviews were conducted with women six months postpartum. Logistic regression analysis was employed to calculate the odds ratio and investigate the differences in the utilization rates of public lactation rooms (PLR) and workplace lactation rooms (WLR) among working mothers over a five-year period, to confirm the effectiveness of public strategies. RESULTS: Comparing the years 2011 and 2016, significant differences in the rates of exclusive breastfeeding (EBF) and any breastfeeding (ABF) among working mothers returning to work after an 8-week maternity leave, depending on whether they used PLR or WLR. The rates were higher in 2016 than in 2011. For mothers who used PLR, the breastfeeding rates for EBF at the second, fourth, and sixth months (2011 vs. 2016: 67.6% vs. 81.1%, 75.0% vs. 86.4%, 77.5% vs. 86.2%) and ABF at the second, fourth, and sixth months (2011 vs. 2016: 60.3% vs. 73.9%, 68.8% vs. 81.3%, 73.7% vs. 85.6%). For mothers who used WLR, the breastfeeding rates for EBF at the second, fourth, and sixth months (2011 vs. 2016: 51.3% vs. 58.7%, 54.7% vs. 61.4%, 57.5% vs. 59.3%) and ABF at the second, fourth, and sixth months (2011 vs. 2016: 48.4% vs. 57.0%, 52.3% vs. 60.5%, 54.1% vs. 62.4%). When comparing 2011 to 2016 from the second to the sixth month postpartum, adjusted odds ratios for EBF (PLR: 4.17-5.23 vs. 4.06-6.22, WLR: 1.71-1.83 vs. 1.30-1.61) and ABF (PLR: 6.44-7.02 vs. 9.27-9.90, WLR: 1.91-1.98 vs. 1.97-1.99) showed differences. CONCLUSION: Lactation support rooms play a vital role in motivating working mothers to sustain breastfeeding upon their return to work. Incentivizing businesses to build additional lactation rooms and offering breastfeeding resources is essential in striving to enhance the global breastfeeding rate.