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Ecdysone-induced protein 93 (E93), known as the 'adult-specifier' transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. Although E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discover that, in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNA is broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we reveal that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis that is necessary to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects, and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.
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Metamorfosis Biológica , Ovario , Reproducción , Animales , Femenino , Reproducción/genética , Metamorfosis Biológica/genética , Ovario/metabolismo , Regulación del Desarrollo de la Expresión Génica , Vitelogénesis/genética , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genéticaRESUMEN
MOTIVATION: The registration of serial section electron microscope images is a critical step in reconstructing biological tissue volumes, and it aims to eliminate complex nonlinear deformations from sectioning and replicate the correct neurite structure. However, due to the inherent properties of biological structures and the challenges posed by section preparation of biological tissues, achieving an accurate registration of serial sections remains a significant challenge. Conventional nonlinear registration techniques, which are effective in eliminating nonlinear deformation, can also eliminate the natural morphological variation of neurites across sections. Additionally, accumulation of registration errors alters the neurite structure. RESULTS: This article proposes a novel method for serial section registration that utilizes an unsupervised optical flow network to measure feature similarity rather than pixel similarity to eliminate nonlinear deformation and achieve pairwise registration between sections. The optical flow network is then employed to estimate and compensate for cumulative registration error, thereby allowing for the reconstruction of the structure of biological tissues. Based on the novel serial section registration method, a serial split technique is proposed for long-serial sections. Experimental results demonstrate that the state-of-the-art method proposed here effectively improves the spatial continuity of serial sections, leading to more accurate registration and improved reconstruction of the structure of biological tissues. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/TongXin-CASIA/EFSR.
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Flujo Optico , Microscopía/métodos , Programas Informáticos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Depression is a debilitating mental illness that poses a serious threat to human health. Nitric Oxide (NO), as an important gasotransmitter, is closely associated with the pathogenesis of depressive disorders. Effective monitoring of NO fluctuation is beneficial for the diagnosis of depression and therapy assessment of antidepressants. Currently, there is a lack of effective methods for rapidly and sensitively identifying NO and elucidating its relationship with depression diseases. Herein, we developed a NIR dye TJ730-based fluorescent probe TJ730-Golgi-NO incorporating benzenesulfonamide as a Golgi-targeted moiety and the thiosemicarbazide group for NO detection. The probe exhibited turn-on fluorescence ability and a large Stokes shift of 158 nm, which shows high sensitivity, selectivity, and rapid response (<1 min) for NO detection. TJ730-Golgi-NO could detect exogenous and endogenous NO in cells stimulated by Glu and LPS, and target Golgi apparatus. Moreover, we disclose a significant increase of NO in the depression model and a weak fluorescence evidenced in the fluoxetine-treated depression mice. This study provides a competent tool for studying the function of NO and helping improve the effective treatment of depression diseases.
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Depresión , Colorantes Fluorescentes , Aparato de Golgi , Óxido Nítrico , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/farmacología , Animales , Óxido Nítrico/metabolismo , Óxido Nítrico/análisis , Ratones , Aparato de Golgi/metabolismo , Depresión/tratamiento farmacológico , Estructura Molecular , Humanos , Modelos Animales de Enfermedad , Masculino , Relación Estructura-Actividad , Rayos Infrarrojos , Relación Dosis-Respuesta a Droga , Imagen Óptica , Células RAW 264.7RESUMEN
OBJECTIVE: Insulin resistance (IR) imposes a significant burden on inflammatory diseases, and the triglyceride-glucose (TyG) index, which is an easily accessible indicator for detecting IR, holds great application potential in predicting the risk of arthritis. The aim of this study is to analyze the association between the TyG index and the risk of new-onset arthritis in the common population aged over 45 using a prospective cohort study design. METHOD: This population-based cohort study involved 4418 participants from the China Health and Retirement Longitudinal Study (from Wave 1 to Wave 4). Multivariate logistic regression models were employed to investigate the association between the TyG index and new-onset arthritis, and RCS analyses were used to investigate potential non-linear relationships. Moreover, decision trees were utilized to identify high-risk populations for incident arthritis. RESULT: Throughout a 7-year follow-up interval, it was found that 396 participants (8.96%) developed arthritis. The last TyG index quartile group (Q4) presented the highest risk of arthritis (OR, 1.39; 95% CI, 1.01, 1.91). No dose-response relationship between the TyG index and new-onset arthritis was identified (Poverall=0.068, Pnon-linear=0.203). In the stratified analysis, we observed BMI ranging from 18.5 to 24 exhibited a heightened susceptibility to the adverse effects of the TyG index on the risk of developing arthritis (P for interaction = 0.035). CONCLUSION: The TyG index can be used as an independent risk indicator for predicting the start of new-onset arthritis within individuals aged 45 and above within the general population. Improving glucose and lipid metabolism, along with insulin resistance, may play a big part in improving the primary prevention of arthritis.
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Artritis , Resistencia a la Insulina , Humanos , Estudios de Cohortes , Estudios Longitudinales , Estudios Prospectivos , Artritis/diagnóstico , Artritis/epidemiología , Glucosa , Factores de Riesgo , Triglicéridos , Glucemia , BiomarcadoresRESUMEN
Early-stage glottic laryngeal carcinoma refers to Tis-T2 lesions without cervical lymph nodes involvement and distant metastasis. Rosiglitazone facilitates expression of anti-inflammatory substances in the body, protecting immune system and improving patient's treatment efficacy and prognosis. We aimed to clarify the influence of rosiglitazone on prognosis of early-stage glottic laryngeal carcinoma. The control group received low-temperature plasma radiofrequency ablation and the observation group additionally received rosiglitazone; 4 mg, 2 times/day for 6 months. After treatment, the observation group showed reduction in the fundamental frequency perturbation and amplitude perturbation and increase in the harmonic-to-noise ratio relative to the control group. Total effective rate was 80.31% and 77.14% for observation and control groups, respectively (P > 0.05). Peripheral blood immune makers were higher in the observation group. The incidence rates of adverse reactions were lower in the observation group. The median survival time was 33 months in control group and 47 months in observation group (P < 0.05). The five-year survival rate was 77.14% in the observation group and 54.29% in the control group (P < 0.05). Rosiglitazone can prolong the survival of early-stage glottic laryngeal carcinoma patients, improving immune function and reducing adverse reactions during treatment.
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Neoplasias Laríngeas , Calidad de Vida , Rosiglitazona , Humanos , Rosiglitazona/farmacología , Rosiglitazona/uso terapéutico , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/mortalidad , Masculino , Persona de Mediana Edad , Femenino , Pronóstico , Anciano , Glotis/patología , Glotis/efectos de los fármacos , Estadificación de Neoplasias , Adulto , Resultado del TratamientoRESUMEN
The redox system is closely related to changes in cellular metabolism. Regulating immune cell metabolism and preventing abnormal activation by adding antioxidants may become an effective treatment for oxidative stress and inflammation-related diseases. Quercetin is a naturally sourced flavonoid with anti-inflammatory and antioxidant activities. However, whether quercetin can inhibit LPS-induced oxidative stress in inflammatory macrophages by affecting immunometabolism has been rarely reported. Therefore, the present study combined cell biology and molecular biology methods to investigate the antioxidant effect and mechanism of quercetin in LPS-induced inflammatory macrophages at the RNA and protein levels. Firstly, quercetin was found to attenuate the effect of LPS on macrophage proliferation and reduce LPS-induced cell proliferation and pseudopodia formation by inhibiting cell differentiation, as measured by cell activity and proliferation. Subsequently, through the detection of intracellular reactive oxygen species (ROS) levels, mRNA expression of pro-inflammatory factors and antioxidant enzyme activity, it was found that quercetin can improve the antioxidant enzyme activity of inflammatory macrophages and inhibit their ROS production and overexpression of inflammatory factors. In addition, the results of mitochondrial morphology and mitochondrial function assays showed that quercetin could upregulate the mitochondrial membrane potential, ATP production and ATP synthase content decrease induced by LPS, and reverse the mitochondrial morphology damage to a certain extent. Finally, Western blotting analysis demonstrated that quercetin significantly upregulated the protein expressions of SIRT1 and PGC-1α, that were inhibited by LPS. And the inhibitory effects of quercetin on LPS-induced ROS production in macrophages and the protective effects on mitochondrial morphology and membrane potential were significantly decreased by the addition of SIRT1 inhibitors. These results suggested that quercetin reprograms the mitochondria metabolism of macrophages through the SIRT1/PGC-1α signaling pathway, thereby exerting its effect of alleviating LPS-induced oxidative stress damage.
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Antioxidantes , Quercetina , Quercetina/farmacología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Lipopolisacáridos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/metabolismo , Estrés Oxidativo , Macrófagos/metabolismo , Transducción de Señal , Adenosina Trifosfato/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismoRESUMEN
BACKGROUND: Polysaccharides are the most widely used additives to enhance the quality of surimi gels. Oat ß-glucan (OG), a functional polysaccharide, is known to affect the gelation characteristics of surimi. However, it has been rarely reported. Therefore, the effect of OG at different levels on gelling properties, protein conformation, and microstructures of silver carp surimi gels were investigated. RESULTS: An increase in the OG content from 0 to 1.0% significantly improved the hardness, springiness, chewiness, puncture properties, storage modulus, and loss modulus of surimi gels. Moreover, the incorporation of OG (0-1.0%) facilitated the unfolding of proteins, resulting in the conformational transformation from α-helix to ß-sheet and ß-turn. Consequently, surimi-OG gels displayed a denser network structure with smaller and more uniform voids. Furthermore, partial free water in the gel network was converted into immobile water, increasing the water-holding capacity. However, a further increase in the OG concentration (1.0-2.0%) resulted in a looser and more uneven network structure with large and numerous cavities. In addition, the whiteness of composite gels decreased with increasing content of OG. CONCLUSION: The addition of 1.0% OG dramatically improved the gelation performance of silver carp surimi, providing a theoretical foundation for the exploitation and manufacture of functional surimi products. © 2023 Society of Chemical Industry.
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Carpas , Proteínas de Peces , Animales , Proteínas de Peces/química , Manipulación de Alimentos/métodos , Geles/química , Conformación Proteica , Agua , Productos Pesqueros/análisisRESUMEN
Humanized mice reconstituted with a functional human immune system (HIS) are instrumental in studying human immunity and immune disorders in vivo. The poor or lack of cross-reactivity between mouse cytokines and human cells limits the development and/or function of human immune cell subsets including human myeloid, natural killer and B cells. Here we explored the potential to achieve long-term production of human cytokines in immunodeficient mice using a transposon-plasmid-based hydrodynamic injection approach. We constructed a transposon-plasmid carrying five human cytokine coding sequences (named PB-5F), and observed that four of the cytokines (granulocyte-macrophage colony-stimulating factor, interleukin (IL)-15, IL-6 and IL-3) were detectable in sera and three (granulocyte-macrophage colony-stimulating factor, IL-15 and IL-6) showed long-term production in immunodeficient mice that received a single hydrodynamic injection of PB-5F plus the transposase plasmid (Super PB). Furthermore, a single injection of PB-5F/Super PB markedly enhanced the reconstitution of human myeloid cells and natural killer cells, and promoted human B-cell maturation in HIS mice. Taken together, our data revealed that hydrodynamic injection of the PB-5F/Super PB vectors may serve as a convenient and efficacious means to promote human immune function in HIS mice.
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Citocinas , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Animales , Citocinas/genética , Humanos , Hidrodinámica , Interleucina-6/genética , Células Asesinas Naturales , Ratones , Plásmidos/genéticaRESUMEN
BACKGROUND: To compare MMA-related gene mutations in MMA children and the population in Qingdao, discuss the blood propionyl carnitine (C3), free carnitine (C0) methionine (MET), the mutual ratio and division difference in normal group, carrier group, and MMA group to analyze the relationship between some hotspot mutations and biochemical indicators. METHODS: In total 3,700 newborns testing negative in tandem mass spectrometry (MS/MS) were selected at random and submitted for testing 8 pathogenic sites in MMACHC and 10 in MMUT. The gene mutations in 84 cases with detected mutation genes and 42 diagnosed children were compared. The levels and concentration distribution of C3, C0, MET, C3/C2, C3/C0, C3/MET in the blood samples of three groups were analyzed as well as the difference of biochemical indicators in newborns with hotspot mutations (c.609A>G, c.482G>A, and c.658-660delAAG). RESULTS: All 8 pathogenic mutations in MMACHC in the population were detected and were basically consistent with the mutation types and frequency order in MMA group. The first three were c.609G>A, c.482G>A, and c.658_660delAAG. There were more types of mutation sites detected in MMA group than carrier group. Five out of 10 MMUT gene mutations were detected in the population, and 9 MMUT gene mutation sites were detected in MMA group. The findings in the two groups and the preset sites were not completely consistent. C3, C0, C3/C2, C3/C0, C3/MET in MMA group were higher than carrier and normal groups, and the difference was statistically significant; the MET in MMA group was lower than carrier and normal groups, and the difference was statistical¬ly significant. Based on the three sets of data distribution graphs, C3, C3/C2, C3/C0, and C3/MET were well distinguished. There were differences in the average C3 and C0 levels between carrier and normal groups, but with an obvious cross distribution in the graphs, and no difference in other indicators. In contrast to non-carrier group, C0, C3, C3/C0, C3/C2, and C3/MET concentration levels were higher in 609A>G mutation group, while MET level was lower, with statistical significance; in c.482G>A mutation group, C3, C3/C0, C3/C2, and C3/MET concentration levels were lower than non-carrier group, while MET level was higher, with statistical significance; in c.658-660delAAG mutation group, C0, C3, C3/C0, C3/C2, MET, and C3/MET concentration levels were not statistically different in contrast to other groups. CONCLUSIONS: The top three mutations in MMA children in Qingdao area are c.609A>G, c.482G>A, c.658-660del AAG mutations in MMAHC; C3, C3/C2, C3/C0 can be used as specific prompt indicators for MMA screening; C3, C3/C2, C3/C0, C3/MET can be used as specific prompt indicators for combined MMA screening; abnormalities in biochemical indicators in hotspot mutation group intuitively explains c.609A>G mutation and early-onset MMA. c.482G>A mutation links with late-onset MMA.
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Errores Innatos del Metabolismo de los Aminoácidos , Espectrometría de Masas en Tándem , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/genética , Niño , Humanos , Recién Nacido , Ácido Metilmalónico , Biología Molecular , Mutación , OxidorreductasasRESUMEN
Neutrophils are involved in the development of endometritis, but it remains unknown how neutrophils induce inflammation and tissue damage. Neutrophil extracellular traps (NETs) clear invading pathogens during infection but induce pyroptosis, leading to inflammation and tissue damage. Thus, our objective was to investigate whether NETs participate in bovine endometrial epithelial cell (BEEC) pyroptosis during endometritis. To confirm this, NETs and caspase-1/4; apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC); nod-like receptor protein-3 (NLRP3); and gasdermin D N-terminal (GSDMD-N), TNF-a, IL-1ß, IL-6, and IL-18 in endometrial tissue were detected. Pathological section and vaginal discharge smears were performed to visually determine endometritis in the uterus. BEECs were stimulated with NETs to induce pyroptosis, which was treated with DNase I against pyroptosis. Caspase-1/4, ASC, NLRP3, GSDMD-N, TNF-a, IL-1ß, IL-6, and IL-18 in BEECs were analyzed in endometrial tissue. The results showed that NET formation, as well as pyroptosis-related proteins and proinflammatory, cytokines were elevated in the endometrial tissue of cows with endometritis. Pathological sections and vaginal discharge smears showed increased neutrophils and plasma cells in the uterus, as well as tissue congestion. In BEECs, NETs increased the level of pyroptosis-related proteins and proinflammatory cytokines and were diminished by DNase I. In summary NETs participate BEEC pyroptosis during endometritis in dairy cows.
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Endometritis , Trampas Extracelulares , Excreción Vaginal , Humanos , Femenino , Bovinos , Animales , Piroptosis , Trampas Extracelulares/metabolismo , Endometritis/veterinaria , Interleucina-18/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Interleucina-6/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Células Epiteliales/metabolismo , Inflamación , Proteínas NLR/metabolismo , Citocinas/metabolismo , Desoxirribonucleasa I/metabolismoRESUMEN
Coherent population trapping (CPT) resonance signals have promise in a wide range of applications involving precision sensing. Generally, the CPT phenomenon occurs in a three-level Λ system with a bichromatic phase-coherent light fields. We theoretically and experimentally studied an Rb vapor-cell-based atomic system involving bichromatic CPT optical fields and an external microwave (MW) field simultaneously. In such a mixing scheme, the coherence of the ground states could be controlled either by the Rabi frequency of the microwave field or by the relative phase between the optical fields and the MW field. Moreover, we investigated the Rabi resonance in this mixing scheme. The Rabi frequency of the MW field can be measured SI (International System of Units)-traceably based on the Rabi resonance lineshape, and thus holds the potential to realize intensity stabilization of the optical field in this system. Simple theoretical models and numerical calculations are also presented to explain the experimental results. There is scope to use the proposed technique in future development of SI-traceable optical field strength standards.
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Glioblastoma multiforme (GBM) is a highly lethal and aggressive tumor of the brain that carries a poor prognosis. Temozolomide (TMZ) has been widely used as a first-line treatment for GBM. However, poor brain targeting, side effects, and drug resistance limit its application for the treatment of GBM. We designed a Temozolomide-conjugated gold nanoparticle functionalized with an antibody against the ephrin type-A receptor 3 (anti-EphA3-TMZ@GNPs) for targeted GBM therapy via intranasal administration. The system can bypass the blood-brain barrier and target active glioma cells to improve the glioma targeting of TMZ and enhance the treatment efficacy, while reducing the peripheral toxicity and drug resistance. The prepared anti-EphA3-TMZ@GNPs were 46.12 ± 2.0 nm and suitable for intranasal administration, which demonstrated high safety to the nasal mucosa in a toxicity assay. In vitro studies showed that anti-EphA3-TMZ@GNPs exhibited significantly enhanced cellular uptake and toxicity, and a higher cell apoptosis ratio has been seen compared with that of TMZ (54.9 and 14.1%, respectively) toward glioma cells (C6). The results from experiments on TMZ-resistant glioma cells (T98G) demonstrated that the IC50 of anti-EphA3-TMZ@GNPs (64.06 ± 0.16 µM) was 18.5-fold lower than that of TMZ. In addition, Western blot analysis also revealed that anti-EphA3-TMZ@GNPs effectively down-modulated expression of O6-methylguanine-DNA methyltransferase and increased chemosensitivity of T98G to TMZ. The antiglioma efficacy in vivo was investigated in orthotopic glioma-bearing rats, and the results demonstrated that the anti-EphA3-TMZ@GNPs prolonged the median survival time to 42 days and increased tumor-cell apoptosis dramatically compared with TMZ. In conclusion, anti-EphA3-TMZ@GNPs could serve as an intranasal drug delivery system for efficacious treatment of GBM.
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Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Glioma/tratamiento farmacológico , Oro/química , Nanopartículas del Metal/química , Receptor EphA3/metabolismo , Temozolomida/farmacología , Administración Intranasal/métodos , Animales , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/metabolismo , Línea Celular , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Glioblastoma/metabolismo , Glioma/metabolismo , Humanos , Masculino , Ratas , Ratas Sprague-Dawley , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Liver xenotransplantation (LXT) is greatly impeded by severe thrombocytopenia, anemia, and coagulopathy. Hepatic phagocytic cells are thought to play an important role in LXT-induced thrombocytopenia and anemia. In this study, we investigated whether the lack of recipient CD47-donor SIRPα interaction, which is known to induce xenograft rejection by macrophages, exacerbates platelet and RBC depletion following LXT. We first addressed this question in the absence of anti-donor immune responses using a syngeneic mouse liver transplantation (LT) model. Neither wild-type (WT) nor CD47KO B6 mice developed thrombocytopenia following LT from WT B6 donors. Although a moderate decline in RBCs was detected following LT, there was no significant difference in RBC counts between WT and CD47KO recipients. Because mouse CD47 is cross-reactive with rat SIRPα, we then compared thrombocytopenia and anemia between WT and CD47KO mice following rat LXT. Unlike syngeneic mouse LT, significant thrombocytopenia and anemia were detected following rat LXT. However, the severities of both platelet and RBC depletions were comparable between WT and CD47KO recipients. Furthermore, WT and CD47KO recipients showed a similar extent of early platelet activation. Our results indicate that CD47-SIRPα signaling does not significantly affect the loss of platelets or RBCs following LXT, suggesting that the limited cross-reactivity between recipient CD47 and donor SIRPα is not a significant risk factor for LXT-induced thrombocytopenia and anemia.
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Anemia , Trombocitopenia , Anemia/etiología , Animales , Antígeno CD47 , Xenoinjertos , Hígado , Ratones , Ratones Noqueados , Fagocitosis , Ratas , Receptores Inmunológicos , Factores de Riesgo , Trombocitopenia/etiología , Trasplante HeterólogoRESUMEN
Increasing evidence indicates that the NOD-like receptors (NLRs) family may act as critical back-up defenses and provide synergistic responses when confronted with persistent danger. However, the precise regulatory mechanism of NLRs and the contribution of NLRs to cancer are still unknown. In our previous study, we found that estrogen receptors (ERs) have a close connection with NLRs in the inflammatory response. Here, ERs are first identified as NLRs transcription regulation factors, both regulate NLRs expression and promote inflammasome co-localization. Furthermore, we identified that NLRP3 was differentially expressed in colon normal and cancer cells, selective ERα antagonist could significantly decrease pro-inflammatory cytokines expression, suppress proliferation and promote apoptosis by inhibited NLRP3 expression and inflammasome activity. In short, the research demonstrates that ERs participate in the NLR-associated signaling pathway in cancer by directly regulating NLRs. Our results provide novel insight into ERs as therapeutic targets in NLR-related inflammation and cancer.
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Carcinogénesis/inmunología , Inflamasomas/inmunología , Proteínas NLR/inmunología , Receptores de Estrógenos/inmunología , Carcinogénesis/patología , Línea Celular Tumoral , Humanos , Inflamasomas/análisis , Inflamación/inmunología , Inflamación/patología , Modelos Moleculares , Proteína con Dominio Pirina 3 de la Familia NLR/análisis , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Proteínas NLR/análisis , Receptores de Estrógenos/análisis , Transducción de SeñalRESUMEN
AIMS: To investigate the clinicopathological features and outcomes of adefovir dipivoxil (ADV)-related renal impairment in Chinese patients. MATERIALS AND METHODS: Clinical, pathological, and follow-up data from 15 patients with ADV-related renal impairment were studied. Proximal renal tubular dysfunction (PRTD) was defined by the presence of at least two of the following four abnormalities: hypophosphatemia, hypouricemia, nondiabetic glucosuria, and proteinuria. RESULTS: All patients were treated for 3 - 15 (mean 6.7) years with daily ADV of 10 mg. Renal impairment manifested as PRTD (12, 80%), elevated serum creatinine (12, 80%), and hematuria (2, 13.3%). Mild to moderate tubulointerstitial injury primarily affecting the proximal tubules by light microscopy, and enlarged, dysmorphic mitochondria with loss and disorientation of cristae by electron microscope were identified in all of our cases. Four patients had pathological evidence of IgA nephropathy. The phosphorus, serum uric acid, and creatinine levels were normalized after ADV cessation in 66.7% (8/12) of affected patients, 27.3% (3/11) of affected patients, and 25% (3/12) of affected patients, respectively; proteinuria was eliminated in 7 of 13 affected patients (53.8%); and glucosuria and hematuria both disappeared in all affected patients. These abnormalities had hardly any recovery, and even aggravated with new-onset glucosuria, new-onset hematuria in 3 patients who replaced ADV with tenofovir. CONCLUSION: Nephrotoxicity developed in patients undergoing long-term ADV treatment and was partially reversible after drug cessation. Tubulointerstitial lesions and heteromorphic mitochondria were the predominant pathological changes. Patients with ADV-induced renal impairment should replace ADV with other antiviral agents other than tenofovir.â©.
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Adenina/análogos & derivados , Antivirales/efectos adversos , Organofosfonatos/efectos adversos , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/patología , Adenina/efectos adversos , Adulto , Creatinina/sangre , Femenino , Glucosuria/inducido químicamente , Hematuria/inducido químicamente , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Hipofosfatemia/inducido químicamente , Túbulos Renales Proximales/patología , Túbulos Renales Proximales/fisiopatología , Masculino , Persona de Mediana Edad , Mitocondrias/patología , Fósforo/sangre , Proteinuria/inducido químicamente , Insuficiencia Renal/fisiopatología , Ácido Úrico/sangreRESUMEN
AGPase catalyzes a key rate-limiting step that converts ATP and Glc-1-p into ADP-glucose and diphosphate in maize starch biosynthesis. Previous studies suggest that AGPase is modulated by redox, thermal and allosteric regulation. However, the phosphorylation of AGPase is unclear in the kernel starch biosynthesis process. Phos-tagTM technology is a novel method using phos-tagTM agarose beads for separation, purification, and detection of phosphorylated proteins. Here we identified phos-tagTM agarose binding proteins from maize endosperm. Results showed a total of 1733 proteins identified from 10,678 distinct peptides. Interestingly, a total of 21 unique peptides for AGPase sub-unit Brittle-2 (Bt2) were identified. Bt2 was demonstrated by immunoblot when enriched maize endosperm protein with phos-tagTM agarose was in different pollination stages. In contrast, Bt2 would lose binding to phos-tagTM when samples were treated with alkaline phosphatase (ALP). Furthermore, Bt2 could be detected by Pro-Q diamond staining specifically for phosphorylated protein. We further identified the phosphorylation sites of Bt2 at Ser10, Thr451, and Thr462 by iTRAQ. In addition, dephosphorylation of Bt2 decreased the activity of AGPase in the native gel assay through ALP treatment. Taking together, these results strongly suggest that the phosphorylation of AGPase may be a new model to regulate AGPase activity in the starch biosynthesis process.
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Endospermo/metabolismo , Glucosa-1-Fosfato Adenililtransferasa/metabolismo , Proteínas de Plantas/metabolismo , Subunidades de Proteína/metabolismo , Proteómica/métodos , Almidón/biosíntesis , Zea mays/metabolismo , Secuencia de Aminoácidos , Anticuerpos/metabolismo , Modelos Biológicos , Fosforilación , Proteínas de Plantas/química , SefarosaRESUMEN
BACKGROUND: A rodent model of photodynamic AION resulting from intravenous verteporfin is presented. The analysis of the morphological function, the pathological changes and the potential mechanism of action were further investigated. METHODS: Photodynamic treatment was conducted on the optic nerve head (ONH) following administration of the photosensitizer. The fellow eye was considered as sham control. Fundus Fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT) and Flash-visual evoked potential (F-VEP) recordings were conducted at different time points. Immunohistochemistry was used to observe apoptotic cell death (TUNEL) and macrophage infiltration (ED-1/Iba-1). Retrograde labeling of retinal ganglion cells (RGCs) was used to evaluate the loss of RGCs. RESULTS: After laser treatment, SD-OCT indicated optic nerve edema, while FFA indicated late leakage of the ONH. F-VEPs were distinctly reduced compared to control eyes. The number of apoptotic RGCs peaked on day 14 (5.71 ± 0.76, p < 0.01). The infiltration of ED-1 and Iba-1 increased on the 3rd day following PDT, while it peaked on day 14 (67.5 ± 9.57 and 77.5 ± 12.58 respectively, p < 0.01). Following 3 weeks of AION, the densities of RGCs in the central retinas of the normal and AION eyes were 3075 ± 298/mm2 and 2078 ± 141/mm2 (p < 0.01), respectively. CONCLUSIONS: Verteporfin photodynamic treatment on rodents ONH can lead to functional, histological, and pathological changes. This type of animal model of AION is easy to establish and stable. It can be used for studying the mechanism and neuroprotective medicine of AION injury.
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Neuropatía Óptica Isquémica/fisiopatología , Fármacos Fotosensibilizantes/toxicidad , Verteporfina/toxicidad , Animales , Modelos Animales de Enfermedad , Potenciales Evocados Visuales/fisiología , Angiografía con Fluoresceína , Rayos Láser , Masculino , Disco Óptico/patología , Ratas Sprague-Dawley , Células Ganglionares de la Retina/patología , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: The present study analyzed the appearances of optical coherence tomography angiography (OCTA) in patients with central serous chorioretinopathy (CSC) based on fluorescein angiography (FA) and indocyanine green angiography (ICGA). METHOD: In the current case series, 54 eyes of 50 patients diagnosed as CSC were evaluated retrospectively. OCTA, FA, and ICGA were performed on each patient. Two trained observers examined the OCTA images independently to confirm and compare the choriocapillary appearance with that on FA/ICGA. Also, the leakage of vessels on FA, perfusion of choroidal blood flow on ICGA, blood flow density, and vascular morphology on OCTA, as well as, the effect of serous retinal detachment (SRD) on imaging were observed. Furthermore, the image findings of contralateral eyes were included. RESULTS: 47/54 eyes (corresponding to 43 patients in 50 patients) were finally diagnosed with CSC that presented a leakage on FA and dilated vessels on ICGA, and the corresponding areas could be recognized on OCTA. However, in some of the cases (15 eyes, 31.9%), a portion of the leakage lesion on FA did not overlap completely with that on OCTA. On the OCTA B-scan, six eyes did not show a choriocapillary flow signal under subretinal fluid (SRF) with a median SRD height of 485 µm, despite the dilated vessels on ICGA. Approximately, 21 contralateral eyes without SRD and leakage presented dilated vessels on ICGA; however, only 13 eyes could be recognized on OCTA. In addition, seven eyes presented CSC on FA/ICGA but manifested explicit abnormal vascularization beneath the retinal pigment epithelium (RPE) on OCTA. CONCLUSION: FA/ICGA remains the gold standard for the diagnosis of CSC and cannot be completely replaced by OCTA. However, in some cases displaying hot-spots CNV, OCTA can contribute toward a definite diagnosis. The SRD height may exert a shielding effect on the choriocapillary flow signals on OCTA. Lasers Surg. Med. 50:987-993, 2018. © 2018 Wiley Periodicals, Inc.
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Coriorretinopatía Serosa Central/diagnóstico por imagen , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Adulto , Anciano , Colorantes , Estudios Transversales , Femenino , Humanos , Verde de Indocianina , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
In this study, the mitochondrial damage effect and mechanism of zearalenone (ZEA) in swine small intestine IPEC-J2 cells in vitro were comprehensively characterized. The analyses revealed that ZEA at high doses (8 and 7 µg/mL) can significantly increase P < 0.05 the malondialdehyde levels and decrease antioxidant enzymes activities after 48 h of exposure. Meanwhile, the reactive oxygen species (ROS) accumulation increased in high dose ZEA-treated groups after 2 h treatment, but decreased due to the ROS-induced mitochondrial damage and the caused cell apoptosis after 48 h of high does ZEA treatment. Moreover, the decreasing of mitochondrial membrane potential (MMP; ΔΨ) in high dose ZEA exposure was observed in line with the increasing ROS production in mitochondria. Results suggest that ZEA exposure can induce mitochondrial damage by reducing antioxidant enzyme activities, accumulation of ROS, and decreasing MMP. The mitochondrial damage had a dramatic concentration-effects relationship with ZEA.
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Apoptosis/efectos de los fármacos , Intestino Delgado/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Zearalenona/toxicidad , Animales , Línea Celular , Intestino Delgado/patología , Mitocondrias/patología , PorcinosRESUMEN
Pyramid-based deformation decomposition is a promising registration framework, which gradually decomposes the deformation field into multi-resolution subfields for precise registration. However, most pyramid-based methods directly produce one subfield per resolution level, which does not fully depict the spatial deformation. In this paper, we propose a novel registration model, called GroupMorph. Different from typical pyramid-based methods, we adopt the grouping-combination strategy to predict deformation field at each resolution. Specifically, we perform group-wise correlation calculation to measure the similarities of grouped features. After that, n groups of deformation subfields with different receptive fields are predicted in parallel. By composing these subfields, a deformation field with multi-receptive field ranges is formed, which can effectively identify both large and small deformations. Meanwhile, a contextual fusion module is designed to fuse the contextual features and provide the inter-group information for the field estimator of the next level. By leveraging the inter-group correspondence, the synergy among deformation subfields is enhanced. Extensive experiments on four public datasets demonstrate the effectiveness of GroupMorph. Code is available at https://github.com/TVayne/GroupMorph.