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Rice is a major food crop in the world. Owing to the shortage of rural labor and the development of agricultural mechanization, direct seeding has become the main method of rice cultivation. At present, the main problems faced by direct seeding of rice are low whole seedling rate, serious weeds, and easy lodging of rice in the middle and late stages of growth. Along with the rapid development of functional genomics, the functions of a large number of genes have been confirmed, including seed vigor, low-temperature tolerance germination, low oxygen tolerance growth, early seedling vigor, early root vigor, resistance to lodging, and other functional genes related to the direct seeding of rice. A review of the related functional genes has not yet been reported. In this study, the genes related to direct seeding of rice are summarized to comprehensively understand the genetic basis and mechanism of action in direct seeding of rice and to lay the foundation for further basic theoretical research and breeding application research in direct seeding of rice.
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Objective: To investigate the correlation between GAL-3, Klotho, calcium and phosphorus indexes and cardiovascular complications in patients with chronic kidney disease (CKD). Methods: This is a retrospective study. Forty patients with CKD and cardiovascular complications admitted to the Affiliated Hospital of Hebei University from February 20, 2022 to February 20, 2023 were selected as the experimental group, and another 40 patients with CKD without cardiovascular complications were selected as the control group. The differences in serum Ca+2, PO- 4, GAL-3 and Klotho levels between the two groups were analyzed, and the correlations between the above indicators levels and creatinine levels were analyzed. The correlation between the above indicators levels and cardiac function classification was analyzed, and analyzed the risk factors of CKD complicated with cardiovascular complications. Results: The levels of Ca+2, PO- 4 and GAL-3 in the experimental group were significantly higher than those in the control group, while the level of Klotho was significantly lower than that in the control group. The levels of Ca+2 and PO- 4 were positively correlated with the level of Creatinine (Cr), while the level of Klotho was negatively correlated with the Cr. The levels of Ca+2 and PO- 4 were positively correlated with cardiac function classification, while the level of Klotho was negatively correlated with cardiac function classification. Logistic regression analysis showed that hypertension, BMI, Cr, Ca+2, PO- 4 and VLDL were risk factors for cardiovascular complications, and Klotho level was a protective factor. Conclusion: A positive correlation can be seen between the levels of Ca+2, PO- 4 and cardiac function classification in patients with CKD. Klotho is a protective factor for cardiovascular diseases.
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BACKGROUND: Indirect Traumatic optic neuropathy (ITON) is a severe disease characterized by a sudden decline of visual function after craniofacial injury. However, the best treatment for ITON is unknown. Endoscopic transnasal optic canal decompression (ETOCD) has gradually been used for ITON treatment worldwide in recent years. OBJECTIVE: To assess the effect of ETOCD on visual acuity in patients with ITON and identify factors that affect prognosis. METHODS: In this study, clinical characteristics of 44 ITON patients who underwent ETOCD in Qilu Hospital of Shandong University were retrospectively analyzed. Factors affecting prognosis were also evaluated. RESULTS: ETOCD treatment improved the vision of 20 (45.5%) patients with no patient suffering from vision deterioration. The mean value of visual acuity (VA) scores improved from 1.57 to 2.39 (P < 0.001). Patients with residual vision had a better VA improvement percent than those without light perception (66.67% versus 34.48%, χ2 = 4.13, P = 0.042). Although shorter duration before ETOCD was associated with better improvement score in ITON patients (r = -0.30, P = 0.044), optic canal fracture (OCF) and optic nerve sheath incision did not affect the prognosis of these patients. Five ITON patients with cerebrospinal fluid rhinorrhea were treated with free nasal mucosal flap during the surgery, and no other severe surgical complication occurred. CONCLUSIONS: ETOCD can effectively and safely improve the vision of ITON patients, patients with residual vision and those treated earlier may benefit more from this surgery.
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Traumatismos del Nervio Óptico , Descompresión Quirúrgica , Humanos , Traumatismos del Nervio Óptico/complicaciones , Traumatismos del Nervio Óptico/cirugía , Estudios Retrospectivos , Hueso EsfenoidesRESUMEN
Lipopolysaccharide (LPS) and lipoteichoic acid (LTA) are key virulence factors of Escherichia coli and Staphylococcus aureus respectively, and both of them could cause inflammatory reaction in bovine mammary glands. In this study, we used bovine mammary epithelial cells (BMECs) as pattern recognition receptors and stimulated them with LPS or LTA to investigate the global transcriptional response variations of BMECs to these two different virulent factors through RNA-Seq analysis. We found 100 differentially expressed genes (DEGs) with 95 up-regulated and 5 down-regulated genes in LPS-treated group, whereas 24 DEGs with 12 up-regulated and 12 down-regulated genes in LTA-treated group compared to control. Although the number and expression changes of DEGs are significantly different between LPS vs Control and LTA vs Control, KEGG pathway enrichment analysis showed the majorities of DEGs in each pair were enriched on cytokine-cytokine receptor interaction, NF-κB signaling pathway, and NOD-like receptor signaling pathway, especially cytokines and chemokines. These results provided a comprehensive analysis of gene expression profiles elicited by LPS and LTA in BMECs, contributing to the understanding of early "pathogen-host" interactions during intramammary infections.
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Células Epiteliales/efectos de los fármacos , Regulación de la Expresión Génica , Lipopolisacáridos/metabolismo , Estrés Fisiológico , Ácidos Teicoicos/metabolismo , Factores de Virulencia/metabolismo , Animales , Bovinos , Células Cultivadas , Células Epiteliales/fisiología , Perfilación de la Expresión Génica , Análisis de Secuencia de ARNRESUMEN
NEW FINDINGS: What is the central question of this study? What is the mechanism of DNA methylation in allergic rhinitis? What is the main finding and its importance? A miR-199-3p-Dnmt3a-STAT3 signalling pathway is involved in ovalbumin-induced allergic rhinitis, and miR-199-3p antagomir can relieve the symptoms in the mouse model. ABSTRACT: Recent research has pointed out the involvement of epigenetic modifications in allergic rhinitis (AR), especially DNA methylation. However, the detailed mechanism has remained largely uncovered. We used ovalbumin (OVA) to induce AR in mouse, and behaviour scores were used to confirm its successful establishment. Histamine and other inflammatory factors were detected to further verify success of the model. Real-time PCR was employed to identify the overexpression of miR-199-3p and subsequent down-regulation of DNA methyltransferase 3a (Dnmt3a). Western blotting was utilized to detect Dnmt3a and signal transducer and activator of transcription 3 (STAT3) at the protein level. Bisulfite sequencing PCR was applied to reveal the methylation status of the Stat3 promoter region. A dual-reporter assay was used to confirm the direct targeting of miR-199-3p on the Dnmt3a mRNA and an antagomir specific to miR-199-3p was injected to rescue the symptoms of AR. The AR model was successfully established in mouse and confirmed by both behaviour and molecular markers. We also found lowered expression of Dnmt3a and consecutive hypomethylation of Stat3 promoter and elevated expression of STAT3, which then led to overexpression of IgE and other inflammatory factors. MicroRNAs that worked on the Dnmt3a 3'-untranslated region were predicted and then verified by dual-reporter assay. Finally injection of a miR-199-3p antagomir successfully attenuated the symptoms of AR. We propose that the miR-199-3p-Dnmt3a-STAT3 signalling pathway is involved in OVA-induced AR.
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ADN (Citosina-5-)-Metiltransferasas/genética , MicroARNs/genética , Ovalbúmina/farmacología , Rinitis Alérgica/inducido químicamente , Rinitis Alérgica/genética , Factor de Transcripción STAT3/genética , Transducción de Señal/genética , Regiones no Traducidas 3'/genética , Animales , Línea Celular , Metilación de ADN/genética , ADN Metiltransferasa 3A , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Endogámicos BALB CRESUMEN
Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss.
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Diferenciación Celular/efectos de los fármacos , Ácidos Cumáricos/farmacología , Gentamicinas , Pérdida Auditiva/inducido químicamente , Células-Madre Neurales/efectos de los fármacos , Células Receptoras Sensoriales/efectos de los fármacos , Animales , Animales Recién Nacidos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cóclea/citología , Cóclea/efectos de los fármacos , Pérdida Auditiva/patología , Ratones , Ratones Endogámicos BALB C , Células-Madre Neurales/fisiología , Neurogénesis/efectos de los fármacos , Células Receptoras Sensoriales/fisiologíaRESUMEN
Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis.
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Células Epiteliales/patología , Fibroblastos/patología , Inflamación/patología , Mastitis Bovina/patología , Animales , Bovinos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Inflamación/genética , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células del Estroma/efectos de los fármacos , Células del Estroma/patología , Ácidos Teicoicos/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Nasal and sinonasal inverted papilloma (NSIP) is a benign tumor in which surface epithelial cells grow downward into the underlying supportive tissue with varying degrees of metaplasia. Human papillomavirus (HPV) has been proposed as the causal agent in the pathogenesis of this disease. Many studies have shown that HPV can activate the Akt/mechanistic target of rapamycin (mTOR) signaling pathway, but the role of this pathway in HPV-associated NSIP is largely unknown. In this study, we enrolled 40 control tissue samples and 80 NSIP tissue samples. HPV genotyping showed that 47 of the 80 examined cases of NSIP were HPV-positive (58.8%), and the most common subtype was HPV11 (20/53, 37.7%). The immunohistochemistry showed statistically significant differences in phosphorylated Akt and phosphorylated S6 ribosomal protein staining among control samples, HPV-positive NSIP and HPV-negative NSIP. The HPV11 L1-L2 plasmid increased the proliferation of normal human nasopharyngeal epithelial NP69-SV40T cells and human nasopharyngeal cancer CNE1 cells. Meanwhile, rapamycin, an mTOR inhibitor, reversed the increased cell proliferation induced by the HPV11 L1-L2 plasmid. Western blot analysis showed that Akt/mTOR/S6 were overexpressed in NP69-SV40T cells and CNE1 cells infected with the HPV11 L1-L2 plasmid. These data demonstrate that HPV promotes cell proliferation through the Akt/mTOR signaling pathway in NSIP.
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Neoplasias Nasales/etiología , Papiloma Invertido/etiología , Papillomaviridae/aislamiento & purificación , Proteínas Proto-Oncogénicas c-akt/fisiología , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/fisiología , Adolescente , Adulto , Anciano , Proliferación Celular , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Nasales/virología , Papiloma Invertido/virología , Papillomaviridae/genética , Estudios Retrospectivos , Adulto JovenRESUMEN
Allergic rhinitis (AR) is one of the common disorders in airway allergic inflammation. The pathogenesis of AR is unclear. It is accepted that immune deregulation is associated with the pathogenesis of AR. Recent reports suggest that a large number of micro RNAs (miR) can regulate immune functions. This study aims to investigate the role of miR-146a in an enforcing immunotherapy of AR. In this study, a mouse AR model was created. The levels of miR-146a in the mouse nasal mucosa were assessed by real time RT-PCR. A specific immunotherapy was performed in AR mice. The results showed that the AR mice had an AR-like inflammation in the nasal mucosa. Compared with naïve mice, markedly lower levels of miR-146a were detected in AR mice. The co-administration with miR-146a significantly enforced the effect of ovalbumin (OVA)-specific immunotherapy on inhibition of AR inflammation in the nasal mucosa. Further analysis showed that miR-146a induced transforming growth factor-ß in dendritic cells; the latter induced naïve CD4(+) T cells to differentiate into regulatory T cells. In conclusion, miR-146a can enforce OVA-specific immunotherapy via inducing antigen-specific regulatory T cells. miR-146a may have therapeutic potential to be used in the immunotherapy of allergic diseases.
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Inmunoterapia , MicroARNs/genética , Rinitis Alérgica/genética , Rinitis Alérgica/inmunología , Animales , Estudios de Casos y Controles , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Modelos Animales de Enfermedad , Epítopos de Linfocito T/inmunología , Expresión Génica , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Inmunoterapia Adoptiva , Recuento de Linfocitos , Masculino , Ratones , Nanopartículas , Mucosa Nasal/citología , Mucosa Nasal/inmunología , Mucosa Nasal/metabolismo , Ovalbúmina/inmunología , Rinitis Alérgica/diagnóstico , Rinitis Alérgica/metabolismo , Rinitis Alérgica/terapia , Especificidad del Receptor de Antígeno de Linfocitos T/inmunología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Vacunas/inmunologíaRESUMEN
This study compares clinical characteristics and survival between patients with and without laryngeal function (LF) preservation during surgical treatment for hypopharyngeal carcinoma. We retrospectively reviewed 485 cases of hypopharyngeal carcinoma treated at a single institution for analysis. There were 337 cases with and 148 cases without LF preservation after surgery. Preservation of LF was complete in 237 patients and partial in 100 patients. There were significant statistical differences between the preservation group and the group without preservation in T-stage (P < 0.001), overall staging (P < 0.001), and tumor sites (P < 0.001) except the N-stage (P = 0.240). The patients with LF preservation had significantly better overall survival (log-rank, P = 0.005) and a lower risk of death than those without LF preservation (HR 0.62, 95% CI 0.43-0.97), after multivariable adjustment. Treatment with surgery in combination with radiotherapy is still the favorable choice for patients with hypopharyngeal carcinoma. The maximal restoration of pharyngoesophageal continuity and function improves survival for patients whose tumors are excised completely for the preservation of LF and laryngeal and pharyngeal reconstruction.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Hipofaríngeas , Laringectomía/métodos , Tratamientos Conservadores del Órgano/métodos , Procedimientos de Cirugía Plástica/métodos , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/fisiopatología , Carcinoma de Células Escamosas/cirugía , China/epidemiología , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/fisiopatología , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Neoplasias Hipofaríngeas/mortalidad , Neoplasias Hipofaríngeas/patología , Neoplasias Hipofaríngeas/fisiopatología , Neoplasias Hipofaríngeas/cirugía , Laringe/fisiopatología , Laringe/cirugía , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Faringe/fisiopatología , Faringe/cirugía , Calidad de Vida , Recuperación de la Función , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello , Análisis de SupervivenciaRESUMEN
To study the species of lanthanum (III) nitrate (La[NO3]3) dispersed in cell media and the effect on the osteoblast differentiation of bone marrow stroma cells (BMSCs). Different La-containing precipitations were obtained by adding various concentrations of La(NO3)3 solutions to Dulbecco's modified Eagle medium (DMEM) or DMEM with fetal bovine serum (FBS). A series of characterisation methods, including dynamic light scattering, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, and protein quantification were employed to clarify the species of the different La-containing precipitations. The primary BMSCs were isolated, and the cell viability, alkaline phosphatase activity, and the formation of a mineralised nodule of BMSCs were tested when treated with different La-containing precipitations. The La(NO3)3 solutions in DMEM could form LaPO4, which exits in the particle formation, while the La(NO3)3 solutions in DMEM with FBS could form a La-PO4-protein compound. When treated with La(NO3)3 solutions in DMEM, the cell viability of the BMSCs was inhibited at the concentrations of 1, 10, and 100 µM at 1 day and 3 days. Meanwhile, the supernatant derived from the La(NO3)3 solutions in DMEM did not affect the cell viability of the BMSCs. In addition, the precipitate derived from the La(NO3)3 solutions in DMEM added to the complete medium inhibited the cell viability of the BMSCs at concentrations of 10 µM and 100 µM. When treated with La(NO3)3 solutions in DMEM with FBS, the derived precipitate and supernatant did not affect the cell viability of the BMSCs, except for the concentration of 100 µM La(NO3)3. The La-PO4-protein formed from the La(NO3)3 solutions in DMEM with FBS inhibited the osteoblast differentiation of BMSCs at the concentration of 1 µM La(NO3)3 (P < 0.05) but had no effect on either the osteoblast differentiation at the concentrations of 0.001 and 0.1 µM or on the formation of a mineralised nodule at all tested concentrations of La(NO3)3. Overall, La(NO3)3 solutions in different cell culture media could form different La-containing compounds: La-PO4 particles (in DMEM) and a La-PO4-protein compound (in DMEM with FBS). The different La-containing compounds caused different effects on the cell viability, osteoblast differentiation, and the formation of a mineralised nodule of the BMSCs. The La-containing precipitation inhibited the osteoblast differentiation by inhibiting the expression of osteoblast-related genes and proteins, providing a theoretical basis for clinical doctors to apply phosphorus-lowering drugs such as lanthanum carbon.
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Células Madre Mesenquimatosas , Nitratos , Ratones , Animales , Nitratos/farmacología , Nitratos/metabolismo , Lantano/farmacología , Lantano/metabolismo , Osteogénesis , Células Cultivadas , Diferenciación Celular , Células de la Médula Ósea , Proliferación Celular , Células del EstromaRESUMEN
To evaluate whether radiomics models based on unenhanced paranasal sinuses CT images could be a useful tool for differentiating inverted papilloma (IP) from chronic rhinosinusitis with polyps (CRSwNP). This retrospective study recruited 240 patients with CRSwNP and 106 patients with IP from three centers. 253 patients from Qilu Hospital were randomly divided into the training set (n = 151) and the internal validation set (n = 102) with a ratio of 6:4. 93 patients from the other two centers were used as the external validation set. The patients with the unilateral disease (n = 115) from Qilu Hospital were selected to further develop a subgroup analysis. Lesion segmentation was manually delineated in CT images. Least absolute shrinkage and selection operator algorithm was performed for feature reduction and selection. Decision tree, support vector machine, random forest, and adaptive boosting regressor were employed to establish the differential diagnosis models. 43 radiomic features were selected for modeling. Among the models, RF achieved the best results, with an AUC of 0.998, 0.943, and 0.934 in the training set, the internal validation set, and the external validation set, respectively. In the subgroup analysis, RF achieved an AUC of 0.999 in the training set and 0.963 in the internal validation set. The proposed radiomics models offered a non-invasion and accurate differential approach between IP and CRSwNP and has some significance in guiding clinicians determining the best treatment plans, as well as predicting the prognosis.
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Pólipos Nasales , Papiloma Invertido , Radiómica , Rinosinusitis , Tomografía Computarizada por Rayos X , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Crónica , Diagnóstico Diferencial , Pólipos Nasales/diagnóstico por imagen , Pólipos Nasales/patología , Papiloma Invertido/diagnóstico por imagen , Papiloma Invertido/patología , Estudios Retrospectivos , Rinosinusitis/diagnóstico por imagen , Rinosinusitis/patología , Tomografía Computarizada por Rayos X/métodosRESUMEN
Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.
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Extracellular acidic pH-activated chloride channels (ICl,acid) have been found in a variety of mammalian cells. In the present study, the expression and regulation of ICl,acid were investigated in THP-1 cells. Patch clamp recordings demonstrated that an extracellular acidic solution induced an outward rectified current, which could be blocked by the Cl(-) channel blocker. The currents exhibited time-dependent facilitation and inactivation. The relative anion permeability of this current followed the sequence Cl(-)>Br(-)>I(-)>gluconate. NADPH oxidase inhibitors did not decrease pH 4.4-induced currents. However, reactive oxygen species (ROS) scavengers and mitochondrial inhibitors inhibited pH 4.4-induced currents. Fluorescence imaging of intracellular ROS and mitochondrial activity confirmed these findings. We conclude that ICl,acid occurs in human THP-1 cells and that ICl,acid may be regulated by intracellular ROS mainly originating from mitochondria.
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Canales de Cloruro/fisiología , Potenciales de la Membrana , Monocitos/fisiología , Especies Reactivas de Oxígeno/metabolismo , Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/farmacología , Ácidos/química , Línea Celular Tumoral , Canales de Cloruro/antagonistas & inhibidores , Humanos , Concentración de Iones de Hidrógeno , Mitocondrias/fisiología , Técnicas de Placa-Clamp , SolucionesRESUMEN
Increased autophagic vacuoles (AVs) occur in injured or degenerating neurons, under both developmental and pathological situations. Although an induced autophagy has been shown in inflammation response to cell factors, the underlying mechanism(s) remain(s) unknown. Here, we show that both cell factor IL-6 and environmental toxin MPP(+) promote the formation of vacuolation in SHSY5Y cells. By electron and immunofluorescent microscopy analyses, we showed that these structures are acid autolysosomes, containing cellular debris, and labeled by LC3 or LAMP1, markers of autophagosomes or lysosomes, respectively. Combining MPP(+) and IL-6 do not further increase vacuolation of SHSY5Y cells, and the vacuolation is less than that in the MPP(+)-treated group. MPP(+)-induced vacuolation results from significant increase in autophagy formation and delay in autophagy degradation, in relation to a decline of the lysosomal activity of arylsulfatase A. At molecular level, we show that this defect in autolysosomal maturation is independent of mammalian target of rapamycin and p38 inhibitions. Most importantly, we provide the first evidence that activation of ERK pathway is sufficient to commit cell to autophagic vacuolation. The sustained activation is required for MPP(+) to disrupt the autophagic pathway. IL-6 also induces a temporary and significant activation of ERK, but not sustained activation, and change sustained activation in MPP(+)-treated group into temporary activation. Taken together, these findings strongly support that IL-6 promotes the maturation of autophagosomes into functional autolysosomes by regulating ERK.
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Autofagia/efectos de los fármacos , Interleucina-6/farmacología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , 1-Metil-4-fenilpiridinio/farmacología , Western Blotting , Línea Celular Tumoral , Cerebrósido Sulfatasa/metabolismo , Flavonoides/farmacología , Humanos , Lisosomas/metabolismo , Lisosomas/ultraestructura , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Microscopía Electrónica , Microscopía Fluorescente , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Fagosomas/metabolismo , Fagosomas/ultraestructura , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Vacuolas/metabolismo , Vacuolas/ultraestructuraRESUMEN
In order to investigate the mechanisms and therapeutic effects of valproate combined with lithium carbonate on mouse model of Parkinson's disease (PD), male C57BL/6 mice were injected into intraperitoneal with valproate (20 µg/ml) combined with lithium carbonate (10 µg/ml) for 7 days following 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) (30 mg/kg) administration, and the effects on motor function were analyzed. Immunohistochemistry and Western blotting were used to detect alterations in the expression of PD biomarkers, including tyrosine hydroxylase (TH), and the level of autophagy was evaluated by the detection of microtubule-associated protein light chain 3 (LC3). In addition, the levels of monoamine neurotransmitters were measured in the striatum using high performance liquid chromatography (HPLC). After MPTP exposure, all groups manifested decreased rolling bar latency and spontaneous activity, in addition to increased pole-climbing time. The combined treatment group exhibited a recovery of rolling bar latency and pole-climbing time. The number of dopaminergic neurons in the substantia nigra following MPTP treatment was higher in the combined treatment group compared with the positive control group (p = .003). Immunoreactivity for LC3 was higher in the combined treatment group than in the controls (p = .003). The concentrations of both striatal dopamine and the dopamine metabolite dihydroxyphenyl acetic acid (DOPAC) were decreased in both MPTP-treated groups compared with the controls. The loss of DOPAC was less severe in the combined treatment group relative to the positive control group (p = .001). Therefore, we infer that valproate combined with lithium carbonate can rescue dopaminergic neurons and ameliorate the loss of DOPAC following MPTP treatment, likely via activation of autophagic/lysosomal pathways.
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Autofagia/fisiología , Carbonato de Litio/administración & dosificación , Intoxicación por MPTP/tratamiento farmacológico , Trastornos Parkinsonianos/tratamiento farmacológico , Ácido Valproico/administración & dosificación , Animales , Autofagia/efectos de los fármacos , Quimioterapia Combinada , Intoxicación por MPTP/metabolismo , Intoxicación por MPTP/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/patología , Distribución AleatoriaRESUMEN
Background: Allergic rhinitis (AR) is an important risk factor for the development of asthma. The "unified airway" theory considers the upper and lower airways as a morphological and functional whole. However, studies exploring biomarkers linking the upper and lower airways in allergic disease are lacking, which may provide insight into the mechanisms underlying AR comorbid asthma. Purpose: To integrate bioinformatics techniques to explore biomarkers in airway allergic diseases, and to provide a molecular etiology profile for preventing the development of asthma in AR patients. Methods: Biomarkers were screened by identifying key genes common between AR and asthma through WGCNA and differential gene analysis. GO and KEGG analyses were performed using DAVID. Immuno-infiltration analysis was performed by CIBERSORTx. The predictive value of CST1 to distinguish Th2-high asthma was determined by ROC curves. GSEA was used to analyze the signaling pathways involved in CST1. TargetScan and miRNet were combined with GSE142237 to construct ceRNA network. CMap was used to explore potential therapeutic drugs. Results: Validation of datasets showed that CST1 was the only gene that was up-regulated in both upper and lower airways in patients with AR and asthma, and correlation heatmaps showed that CST1 was the gene with the highest sum of correlation coefficients. GO and KEGG analysis demonstrated that the lower airways of AR patients were mainly involved in inflammatory and immune responses, similar to asthma. Immune infiltration showed that CST1 was mainly positively correlated with activated CD4 memory T cells. According to the ROC curve, CST1 showed excellent diagnostic efficiency for Th2-high asthma. GSEA indicated that CST1 was involved in the FcϵRI signaling pathway and O-glycan biosynthesis. A ceRNA network including the lncRNAs KCNQ1OT1 and NEAT1 was constructed. Four drugs, including verrucarin-A, had the potential to prevent the development of asthma in AR patients. In addition, corticosteroids were found to downregulate CST1 expression. Conclusion: CST1 plays a key role in the development of AR comorbid asthma and may be a biomarker for airway allergic diseases. Targeted treatment of CST1 has the potential to prevent the development of asthma in AR patients and deserves further study.
Asunto(s)
Asma , Rinitis Alérgica , Humanos , Transcriptoma , Rinitis Alérgica/genética , Sistema Respiratorio , BiomarcadoresRESUMEN
Chronic rhinosinusitis (CRS) is characterized by poor prognosis and propensity for recurrence even after surgery. Identification of those CRS patients with high risk of relapse preoperatively will contribute to personalized treatment recommendations. In this paper, we proposed a multi-task deep learning network for sinus segmentation and CRS recurrence prediction simultaneously to develop and validate a deep learning radiomics-based nomogram for preoperatively predicting recurrence in CRS patients who needed surgical treatment. 265 paranasal sinuses computed tomography (CT) images of CRS from two independent medical centers were analyzed to build and test models. The sinus segmentation model achieved good segmentation results. Furthermore, the nomogram combining a deep learning signature and clinical factors also showed excellent recurrence prediction ability for CRS. Our study not only facilitates a technique for sinus segmentation but also provides a noninvasive method for preoperatively predicting recurrence in patients with CRS.
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High-salinity and blast disease are two major stresses that cause dramatic yield loss in rice production. GF14 (14-3-3) genes have been reported to play important role in biotic and abiotic stresses in plants. However, the roles of OsGF14C remain unknown. To understand the functions and regulatory mechanisms of OsGF14C in regulating salinity tolerance and blast resistance in rice, we have conducted OsGF14C-overexpressing transgenic experiments in the present study. Our results showed that overexpression of OsGF14C enhanced salinity tolerance but reduced blast resistance in rice. The enhanced salinity tolerance is related to the reduction of methylglyoxal and Na+ uptake instead of exclusion or compartmentation and the negative role of OsGF14C in blast resistance is associated with the suppression of OsGF14E, OsGF14F and PR genes. Our results together with the results from the previous studies suggest that the lipoxygenase gene LOX2 which is regulated by OsGF14C may play roles in coordinating salinity tolerance and blast resistance in rice. The current study for the first time revealed the possible roles of OsGF14C in regulating salinity tolerance and blast resistance in rice, and laid down a foundation for further functional study and crosstalk regulation between salinity and blast resistance in rice.
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The porous iron-based metal organic frameworks (NH2-MIL-101(Fe)), which consists of 2-amino benzene dicarboxylic acid (H2BDC-NH2) and ferrous ions were synthesized through one-step hydrothermal method. The surface area and pore volume of as-synthesized NH2-MIL-101(Fe) were 66.48 m2/g and 0.09 cm3/g, respectively. The excellent photocatalytic performance endows NH2-MIL-101(Fe) to generate hydroxyl radical (â¢OH), which then acting as efficiently active sites for azo dye degradation in wastewater. Meanwhile, the outstanding stability ability of NH2-MIL-101(Fe) indicates the potential candidate for wastewater treatment.