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The development of metal complexes for photosynthesis of hydrogen peroxide (H2O2) from pure water and oxygen using solar energy, especially in the absence of any additives (e.g., acid, co-catalysts, and sacrificial agents), is a worthwhile pursuit, yet still remains highly challenging. More importantly, the O2 evolution from the water oxidation reaction has been impeded by the classic bottleneck, the photon-flux-density problem of sunlight that could be attributed to rarefied solar radiation for a long time. Herein, we reported synthesis of boron dipyrromethene (BODIPY)-based cyclic trinuclear silver complexes (Ag-CTC), and they exhibited strong visible-light absorption ability, a suitable energy bandgap, excellent photochemical properties and efficient charge separation ability. The integration of BODIPY motifs as oxygen reduction reaction sites and silver ions as water oxidation reaction sites allows Ag-CTC to photosynthesize H2O2 either from pure water or from sea water in the absence of any additives with a high H2O2 production rate of 183.7 and 192.3 µM h-1, which is higher than that of other reported metal-based photocatalysts. The photocatalytic mechanism was systematically and ambiguously investigated by various experimental analyses and density functional theory (DFT) calculations. Our work represents an important breakthrough in developing a new Ag photocatalyst for the transformation of O2 into H2O2 and H2O into H2O2.
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The development of novel metal-organic frameworks (MOFs) as efficient photocatalysts for hydrogen peroxide production from water and oxygen is particularly interesting, yet remains a challenge. Herein, we have prepared four cyclic trinuclear units (CTUs) based MOFs, exhibiting good light absorption ability and suitable band gaps for photosynthesis of H2O2. However, Cu-CTU-based MOFs are not able to photocatalyzed the formation of H2O2, while the alteration of metal nodes from Cu-CTU to Ag-CTU dramatically enhances the photocatalytic performance for H2O2 production and the production rates can reach as high as 17476â µmol g-1 h-1 with an apparent quantum yield of 4.72 %, at 420â nm, which is much higher than most reported MOFs. The photocatalytic mechanism is comprehensively studied by combining the isotope labeling experiments and DFT calculation. This study provides new insights into the preparation of MOF photocatalysts with high activity for H2O2 production through molecular engineering.
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The major depressive disorder (MDD) is a common and severe mental disorder. To identify a reliable biomarker for MDD is important for early diagnosis and prevention. Given easy access and high reproducibility, the structural magnetic resonance imaging (sMRI) is an ideal method to identify the biomarker for depression. In this study, sMRI data of first episode, treatment-naïve 66 MDD patients and 54 sex-, age-, and education-matched healthy controls (HC) were used to identify the differences in gray matter volume (GMV), group-level, individual-level covariance connections. Finally, the abnormal GMV and individual covariance connections were applied to classify MDD from HC. MDD patients showed higher GMV in middle occipital gyrus (MOG) and precuneus (PCun), and higher structural covariance connections between MOG and PCun. In addition, the Allen Human Brain Atlas (AHBA) was applied and revealed the genetic basis for the changes of gray matter volume. Importantly, we reported that GMV in MOG, PCun and structural covariance connectivity between MOG and PCun are able to discriminate MDD from HC. Our results revealed structural underpinnings for MDD, which may contribute towards early discriminating for depression.
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Biomarcadores , Trastorno Depresivo Mayor , Sustancia Gris , Imagen por Resonancia Magnética , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Adulto , Adulto Joven , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Vías Nerviosas/patología , Vías Nerviosas/diagnóstico por imagen , Tamaño de los Órganos , Persona de Mediana EdadRESUMEN
Yeast extract is increasingly becoming an attractive source for unraveling novel umami peptides that are healthier and more nutritious than traditional seasonings. In the present study, a strategy for screening novel umami peptides was established using mass spectrometry-based peptidomics combined with molecular interaction modeling, emphasizing on smaller peptides than previously reported. Four representative novel umami peptides of FE, YDQ, FQEY, and SPFSQ from yeast extract (Saccharomyces cerevisiae) were identified and validated by sensory evaluation, with thresholds determined as 0.234 ± 0.045, 0.576 ± 0.175, 0.327 ± 0.057 and 0.456 ± 0.070 mmol/L, respectively. Hydrogen and ionic bonds were the main characteristic interactions between the umami peptides and the well-recognized receptor T1R1/T1R3, in which Asp 110, Thr 112, Arg 114, Arg 240, Lys 342, and Glu 264 were the key sites in ligand-receptor recognition. Our study provides accurate sequences of umami peptides and molecular interaction mechanism for the umami effect.
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Péptidos , Saccharomyces cerevisiae , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/metabolismo , Péptidos/química , Humanos , Gusto , Modelos Moleculares , Aromatizantes/química , Aromatizantes/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Masculino , Proteómica , Femenino , Secuencia de AminoácidosRESUMEN
There is no detailed study on how tidal volume (VT) affects patients during one-lung ventilation (OLV). The present study conducted a meta-analysis to assess the effect of VT on physiology and clinical outcomes in OLV patients. Databases until February 2023 were retrieved from PubMed, Cochrane Library and Web of Science. Randomized controlled trials comparing the application of low and high VT ventilation in adults with OLV were performed. Demographic variables, VT, physiology, and clinical outcomes were retrieved. The random-effects model calculated the summary of odds ratios with 95% confidence intervals (CI) and mean difference with standard deviation. A total of 12 studies involving a total of 876 participants met the inclusion criteria. Low VT ventilation was associated with decreased risk of acute lung injury [relative risk 0.50, 95% CI (0.28, 0.88), P=0.02]. Low VT ventilation decreased the driving pressure (ΔP) and peak pressure (Ppeak) and improved arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2). Furthermore, the present study suggested that a significant difference in blood IL-6 was observed between low and high VT ventilation [mean difference, -35.51 pg/ml, 95% CI (-66.47, -4.54 pg/ml), P=0.02]. A decrease in the length of stay at the hospital occurred in the low VT group when set to 4-5 ml/kg. In the OLV patients, low VT ventilation decreased the risk of acute lung injury, blood IL-6, ΔP and Ppeak, and improved PaO2/FiO2. Furthermore, when low VT was set to 4-5 ml/kg, the length of stay at the hospital decreased.
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This paper aims to explore the cooperative use of agricultural waste and nanomaterials to improve environmental sustainability. The introduction highlights global environmental challenges and the objectives of integrating the two are highlighted. Valorization of agricultural waste is considered to reduce waste generation, while nanomaterials act as conversion catalysts that help to increase the efficiency of waste conversion and environmental remediation. In addition, synergistic approaches are discussed, including the combination of agricultural waste and nanomaterials, as well as the concept of enhanced resource management. The paper also presents case studies that demonstrate the success of such synergistic applications in pollution control and environmental remediation. Despite the challenges and risks, this approach can provide new ways to create more sustainable and resilient environments through the integration of resources, interdisciplinary cooperation and policy support.
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Restauración y Remediación Ambiental , Nanoestructuras , Administración de Residuos , Contaminación Ambiental/prevención & control , AgriculturaRESUMEN
Excessive intake of oil, salt and sugar is closely associated with the prevalence of non-communicable chronic diseases (NCDs). Canteen staff's knowledge, attitude and practice (KAP) about oil, salt and sugar directly affect the content in dishes and the consumers' intake. However, no valid questionnaire is used to assess KAP among canteen staff about the "oil, salt and sugar". Therefore, the present study aimed to establish and validate a questionnaire to evaluate the KAP of canteen staff about the "oil, salt and sugar". This cross-sectional study was conducted among canteen staff randomly selected from three college canteens. Participants completed the questionnaire and retested it two weeks later. Internal and test-retest reliability were assessed using Cronbach's α and Pearson correlation coefficients, respectively. Validity was assessed using the exploratory factor analysis. 100 participants finished the questionnaire, of which 66% were females with a mean age of 40.3 ± 10.5 years. The Cronbach's α coefficients of the total questionnaire and Knowledge, Attitude and Practice dimensions were 0.822, 0.830, 0.752 and 0.700, respectively. The test-retest reliability coefficient was 0.968. In exploratory factor analysis, nine common factors were extracted, with 26 items, and the cumulative contribution rate was 70.9%. The questionnaire had a satisfactory property for measuring the KAP of the "oil, salt and sugar" among canteen staff in China.
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Conocimientos, Actitudes y Práctica en Salud , Azúcares , Femenino , Humanos , Adulto , Persona de Mediana Edad , Masculino , Reproducibilidad de los Resultados , Estudios Transversales , Encuestas y Cuestionarios , Psicometría/métodosRESUMEN
Clathrin-mediated vesicular formation and trafficking are responsible for molecular cargo transport and signal transduction among organelles. Our previous study shows that CHLOROPLAST VESICULATION (CV)-containing vesicles (CVVs) are generated from chloroplasts for chloroplast degradation under abiotic stress. Here, we show that CV interacts with the clathrin heavy chain (CHC) and induces vesicle budding toward the cytosol from the chloroplast inner envelope membrane. In the defective mutants of CHC2 and the dynamin-encoding DRP1A, CVV budding and releasing from chloroplast are impeded. The mutations of CHC2 inhibit CV-induced chloroplast degradation and hypersensitivity to water stress. Moreover, CV-CHC2 interaction is impaired by the oxidized GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPC). GAPC1 overexpression suppresses CV-mediated chloroplast degradation and hypersensitivity to water stress, while CV silencing alleviates the hypersensitivity of the gapc1gapc2 plant to water stress. Together, our work identifies a pathway of clathrin-assisted CVV budding outward from chloroplast, which is involved in chloroplast degradation and stress response.
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Proteínas de Arabidopsis , Arabidopsis , Humanos , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Deshidratación/metabolismo , Cloroplastos/metabolismo , Clatrina/metabolismo , Endocitosis/fisiologíaRESUMEN
Nanotechnology emerges as an important way to safeguard global food security amid the escalating challenges posed by the expansion of the global population and the impacts of climate change. The perfect fusion of this breakthrough technology with traditional agriculture promises to revolutionize the way agriculture is traditionally practiced and provide effective solutions to the myriad of challenges in agriculture. Particularly noteworthy are the applications of nano-fertilizers and pesticides in agriculture, which have become milestones in sustainable agriculture and offer lasting alternatives to traditional methods. This review meticulously explores the key role of nano-fertilizers and pesticides in advancing sustainable agriculture. By focusing on the dynamic development of nanotechnology in the field of sustainable agriculture and its ability to address the overarching issue of global food security, this review aims to shed light on the transformative potential of nanotechnology to pave the way for a more resilient and sustainable future for agriculture.
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Dysfunction of glutamatergic synaptic plasticity in basolateral amygdala (BLA) constitutes a critical pathogenic mechanism underlying the depression-like behaviors induced by chronic pain. Astrocytes serve as an important supporting cell modulating glutamatergic synaptic transmission. Here, we found that peripheral spared nerve injury (SNI) induced astrocyte activation to release IL-6 in BLA. Inhibition of astrocyte activity attenuated SNI-induced IL-6 overexpression and depression-like behaviors. Moreover, SNI enhanced the abundance of DHHC2 in synaptosome and DHHC3 in Golgi apparatus, promoted PSD-95 palmitoylation, and increased the recruitment of GluR1 and NR2B at synapses. Suppression of IL-6 or PSD-95 palmitoylation attenuated the synaptic accumulation of GluR1 and NR2B in BLA and improved depression-like behaviors induced by SNI. Furthermore, IL-6 downstream PI3K increased the expression of DHHC3 in Golgi apparatus and facilitated the interaction of palmitoylated PSD-95 with GluR1 and NR2B at synapses. These findings collectively suggested that SNI activated astrocyte to release IL-6 in BLA, which promoted PSD-95 palmitoylation and enhanced the synaptic trafficking of GluR1 and NR2B, and subsequently mediated the depression-like behaviors induced by nerve injury.
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BACKGROUND: Grain shape is a critical agronomic trait affecting grain yield and quality. Exploration and functional characterization of grain shape-related genes will facilitate rice breeding for higher quality and yield. RESULTS: Here, we characterized a recessive mutant named Oat-like rice for its unique grain shape which highly resembles oat grains. The Oat-like rice displayed abnormal floral organs, an open hull formed by remarkably elongated leafy lemmas and paleae, occasionally formed conjugated twin brown rice, an aberrant grain shape and a low seed setting rate. By map-based cloning, we discovered that Oat-like rice harbors a novel allele of OsMADS1 gene (OsMADS1Olr), which has a spontaneous point mutation that causes the substitution of an amino acid that is highly conserved in the MADS-box domain of the MADS-box family. Further linkage analysis indicated that the point mutation in the OsMADS1Olr is associated with Oat-like rice phenotype, and expression analysis of the OsMADS1 by qRT-PCR and GUS staining also indicated that it is highly expressed in flower organs as well as in the early stages of grain development. Furthermore, OsMADS1Olr-overexpressing plants showed similar phenotypes of Oat-like rice in grain shape, possibly due to the dominant negative effect. And OsMADS1-RNAi plants also displayed grain phenotypes like Oat-like rice. These results suggested that OsMADS1Olr is responsible for the Oat-like rice phenotype including aberrant grain shape. Moreover, the expression levels of representative genes related to grain shape regulation were apparently altered in Oat-like rice, OsMADS1Olr-overexpressing and OsMADS1-RNAi transgenic plants. Finally, compared with Oat-like rice, OsMADS1Olr-overexpressing and OsMADS1-RNAi plants, mild phenotype of seed-specific OsMADS1-RNAi transgenic plants indicated that OsMADS1 may has has a direct regulation role in grain development and the grain phenotypes of Oat-like rice, OsMADS1Olr-overexpressing and OsMADS1-RNAi plants are majorly caused by the abnormal lemma and palea development. CONCLUSIONS: Altogether, our results showed that grain shape and a low seed setting rate of the notable 'Oat-like rice' are caused by a spontaneous point mutation in the novel allele OsMADS1Olr. Furthermore, our findings suggested that OsMADS1 mediates grain shape possibly by affecting the expression of representative genes related to grain shape regulation. Thus, this study not only revealed that OsMADS1 plays a vital role in regulating grain shape of rice but also highlighted the importance and value of OsMADS1 to improve the quality and yield of rice by molecular breeding.
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BACKGROUND: Persistent peripheral CD4+T cell differentiation towards T helper (Th)2 rather than Th1 has been proved to be related to immunosuppression and poor prognosis in sepsis. However, it is unclear whether these circulating Th1 and Th2 subtype accumulations differed in septic populations of distinct infection sites and presented different associations with outcomes among patients with pulmonary versus nonpulmonary sepsis. METHODS: From a secondary analysis of a prospective observational study, seventy-four previously immunocompetent patients with community-acquired severe sepsis within 24 hours upon onset were enrolled. Whole blood was collected on the admission day (D0), 3rd day (D3), and 7th day (D7). The patients were classified as pulmonary (n = 52) and nonpulmonary sepsis (n = 22). Circulating Th1 and Th2 populations were evaluated by flow cytometry, and clinical data related to disease severity and inflammatory response were collected. The associations of circulating Th1 and Th2 subset accumulations with distinct infection sites or outcomes within subgroups were explored. RESULTS: Patients with pulmonary sepsis held similar disease severity and 28-day mortality with those of nonpulmonary sepsis. Of note is the finding that circulating Th2 levels on D7 (P = 0.04) as well as Th2/Th1 on D3 (P = 0.01) and D7 (P = 0.04) were higher in the pulmonary sepsis compared with nonpulmonary sepsis while Th1 levels were lower on D0, D3, and D7 (P = 0.01, <0.01, and =0.05, respectively). Compared to 28-day survivors, higher Th2/Th1 driven by increased Th2 were observed among 28-day nonsurvivors on D3 and D7 in both groups. The association between circulatory Th2 populations or Th2/Th1 and 28-day death was detected in pulmonary sepsis (P < 0.05, HR > 1), rather than nonpulmonary sepsis. CONCLUSIONS: Circulating Th2 accumulation was more apparent among pulmonary sepsis while nonpulmonary sepsis was characterized with the hyperactive circulating Th1 subset among previously immunocompetent patients. This finding suggested that circulating Th1 and Th2 subset accumulations vary in septic subgroups with different infection sites.
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Sepsis/sangre , Células TH1/metabolismo , Células Th2/metabolismo , Anciano , Anciano de 80 o más Años , Linfocitos T CD4-Positivos/metabolismo , Enfermedades Transmisibles/sangre , Enfermedades Transmisibles/inmunología , Enfermedades Transmisibles/patología , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sepsis/inmunología , Sepsis/patologíaRESUMEN
BACKGROUND: Light provides the energy for photosynthesis and determines plant morphogenesis and development. Low light compromises photosynthetic efficiency and leads to crop yield loss. It remains unknown how rice responds to low light stress at a proteomic level. RESULTS: In this study, the quantitative proteomic analysis with isobaric tags for relative and absolute quantitation (iTRAQ) was used and 1221 differentially expressed proteins (DEPs) were identified from wild type rice plants grown in control or low light condition (17% light intensity of control), respectively. Bioinformatic analysis of DEPs indicated low light remarkably affects the abundance of chloroplastic proteins. Specifically, the proteins involved in carbon fixation (Calvin cycle), electron transport, and ATPase complex are severely downregulated under low light. Furthermore, overexpression of the downregulated gene encoding rice ß subunit of glyceraldehyde-3-phosphate dehydrogenase (OsGAPB), an enzyme in Calvin cycle, significantly increased the CO2 assimilation rate, chlorophyll content and fresh weight under low light conditions but have no obvious effect on rice growth and development under control light. CONCLUSION: Our results revealed that low light stress on vegetative stage of rice inhibits photosynthesis possibly by decreasing the photosynthetic proteins and OsGAPB gene is a good candidate for manipulating rice tolerance to low light stress.
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Emerging evidence has indicated that colony-stimulating factor-1 (CSF1) modulates neuroinflammation in the central nervous system and the development of neuropathic pain, while the underlying mechanism remains unknown. Here, we identified the increased expression of CSF1 derived from activated astrocytes in the ipsilateral dorsal horn in rats with spinal nerve ligation (SNL). Suppression of CSF1 expression alleviated neuroinflammation, neuronal hyperexcitability, and glutamatergic receptor subunit upregulation in the dorsal horn and improved SNL-induced pain behavior. We also found reduced miR-214-3p expression in the ipsilateral dorsal horn following an SNL procedure; miR-214-3p directly bound to the 3'-UTR of CSF1 mRNA and negatively regulated CSF1 expression. Intrathecal delivery of miR-214-3p mimic reversed the enhanced expression of CSF1 and astrocyte overactivity and alleviated the IL-6 upregulation and pain behavior induced by SNL. Moreover, suppression of spinal miR-214-3p increased astrocyte reactivity, promoted CSF1 and IL-6 production, and induced pain hypersensitivity in naive animals. Furthermore, SNL induced the expression of DNA methyltransferase 3a (DNMT3a) that was associated with the hypermethylation of the miR-214-3p promoter, leading to reduced miR-214-3p expression in the model rodents. Treatment with the DNMT inhibitor zebularine significantly reduced cytosine methylation in the miR-214-3p promoter; this reduced methylation consequently increased the expression of miR-214-3p and decreased the content of CSF1 in the ipsilateral dorsal horn and, further, attenuated IL-6 production and pain behavior in rats with SNL. Together, our data indicate that the DNMT3a-mediated epigenetic suppression of miR-214-3p enhanced CSF1 production in astrocytes, which subsequently induced neuroinflammation and pain behavior in SNL model rats.
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Astrocitos/metabolismo , Epigénesis Genética , Hiperalgesia/metabolismo , Factor Estimulante de Colonias de Macrófagos/metabolismo , MicroARNs/metabolismo , Neuralgia/metabolismo , Traumatismos de los Nervios Periféricos/complicaciones , Regulación hacia Arriba , Animales , Hiperalgesia/etiología , Hiperalgesia/genética , Factor Estimulante de Colonias de Macrófagos/genética , Masculino , MicroARNs/genética , Neuralgia/etiología , Neuralgia/genética , Ratas , Ratas Sprague-Dawley , Nervios Espinales/lesionesRESUMEN
BACKGROUND: Low differentiation rates of mesenchymal stem cells (MSCs) limit their therapeutic effects on patients in clinical studies. Our previous study demonstrated that overexpressing p130 or E2F4 affected the multipotential differentiation of MSCs, and the underlying mechanism was attributed to the regulation of the G1 phase. Improving the efficiency of MSC differentiation into epithelial cells is considered to be a new method. Therefore, this study was conducted to evaluate the effects of overexpressing p130 or E2F4 in MSCs on improving re-epithelization in lipopolysaccharide (LPS)-induced ARDS animals. METHODS: Mouse MSCs (mMSCs) stably transfected with p130 and E2F4 were transplanted intratracheally into LPS-induced ARDS mice. After 7 and 14 days, the mice were sacrificed, and the histopathology of the lungs was assessed by haematoxylin-eosin staining and lung injury scoring. Homing and differentiation of mMSCs were analysed by labelling and tracking mMSCs with NIR815 dye and immunofluorescent staining. Surfactant proteins A and C and occludin in the lungs were assessed by western blot. Permeability was evaluated by analysing the protein concentration of BALF using ELISA. Alveolar fluid clearance was assessed by absorbance measurements of BALF. Lung fibrosis was assessed by Masson's trichrome staining and Ashcroft scoring. RESULTS: The engraftment of mMSCs overexpressing p130 or E2F4 led to attenuated histopathological impairment of the lung tissue, and the lung injury scores of the LPS+mBM-MSC-p130 and LPS+mBM-MSC-E2F4 groups were also decreased (p < 0.05). Overexpression of p130 or E2F4 also increased the retention of mMSCs in the lung (p < 0.05), increased differentiation into type II alveolar epithelial cells (p < 0.05), and improved alveolar epithelial permeability (p < 0.05). Additionally, mMSCs overexpressing p130 or E2F4 inhibited lung fibrosis according to the deposition of collagen and the fibrosis score in the lungs (p < 0.05). CONCLUSION: Overexpressing p130 or E2F4 in mMSCs could further improve the injured structure and function of epithelial cells in the lungs of ARDS mice as a result of improved differentiation of mMSCs into epithelial cells.
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Células Epiteliales Alveolares/metabolismo , Diferenciación Celular , Factor de Transcripción E2F4/biosíntesis , Expresión Génica , Lipopolisacáridos/toxicidad , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Síndrome de Dificultad Respiratoria , Proteína p130 Similar a la del Retinoblastoma/biosíntesis , Aloinjertos , Células Epiteliales Alveolares/patología , Animales , Factor de Transcripción E2F4/genética , Masculino , Células Madre Mesenquimatosas/patología , Ratones , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/genética , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/terapia , Proteína p130 Similar a la del Retinoblastoma/genéticaRESUMEN
Certain microRNAs (miRs) have important roles in the maintenance of bone development and metabolism, and a variety of miRs are known to be deregulated in diabetes. The present study investigated the role of miR2033p in the regulation of bone loss by assessing jaw bones of a rat model of type 2 diabetes. The results indicated that miR2033p inhibited osteogenesis in the jaws of diabetic rats and in rat bone marrow mesenchymal stem cells cultured in highglucose medium. A luciferase re-porter assay was used to verify the bioinformatics prediction that miR2033p targets the 3'untranslated region of Smad1, which is an important mediator of the bone morphogenetic protein (BMP)/Smad pathway. Overexpression of Smad1 attenuated the miR2033pmediated suppres-sion of osteogenic differentiation. It was therefore indicated that the BMP/Smad pathway is attenuated and the transforming growth factorß/activin pathway is promoted by Smad1 reduction. Taken together, it was indicated that miR2033p inhibits osteogenesis in jaw bones of diabetic rats by targeting Smad1 to inhibit the BMP/Smad pathway.
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Diabetes Mellitus Experimental/genética , Maxilares/metabolismo , MicroARNs/metabolismo , Osteogénesis/genética , Proteína Smad1/genética , Animales , Secuencia de Bases , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Perfilación de la Expresión Génica , Glucosa/toxicidad , Masculino , Mandíbula/metabolismo , MicroARNs/genética , Modelos Biológicos , Osteogénesis/efectos de los fármacos , Ratas Sprague-Dawley , Proteína Smad1/metabolismoRESUMEN
Accumulation of microglia occurs in the dorsal horn in the rodent model of chronic post ischemic pain (CPIP), while the mechanism how microglia affects the development of persistent pain largely remains unknown. Here, using a rodent model of CPIP induced by ischemia-reperfusion (IR) injury in the hindpaw, we observed that microglial accumulation occurred in the ipsilateral dorsal horn after ischemia 3h, and in ipsilateral and contralateral dorsal horn in the rats with ischemia 6h. The accumulated microglia released BDNF, increased neuronal excitability in dorsal horn, and produced pain behaviors in the modeled rodents. We also found significantly increased signaling mediated by astrocytic colony-stimulating factor-1 (CSF1) and microglial CSF1 receptor (CSF1R) in dorsal horn in the ischemia 6h modeled rats. While exogenous M-CSF induced microglial activation and proliferation, BDNF production, neuronal hyperactivity in dorsal horn and behavioral hypersensitivity in the naïve rats, inhibition of astrocytic CSF1/microglial CSF1R signaling by fluorocitric or PLX3397 significantly suppressed microglial activation and proliferation, BDNF upregulation, and neuronal activity in dorsal horn, as well as the mechanical allodynia and thermal hyperalgesia, in the rats with ischemia 6h. Collectively, these results demonstrated that glial CSF1/CSF1R pathway mediated the microglial activation and proliferation, which facilitated the nociceptive output and contributed to the chronic pain induced by IR injury.
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Dolor Crónico/metabolismo , Factores Estimulantes de Colonias/metabolismo , Receptores del Factor Estimulante de Colonias/metabolismo , Animales , Astrocitos/metabolismo , Conducta Animal/fisiología , Sensibilización del Sistema Nervioso Central/fisiología , Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Hiperalgesia/metabolismo , Isquemia/fisiopatología , Factor Estimulante de Colonias de Macrófagos/metabolismo , Masculino , Microglía/metabolismo , Neuralgia/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Asta Dorsal de la Médula Espinal/metabolismo , Regulación hacia ArribaRESUMEN
Chronic pain is the most prominent and disabling symptom in the patients with osteoarthritis (OA), and the underlying mechanism largely remains unclear. Interleukin-6 (IL-6), a proinflammatory cytokine, is critically involved in the development and maintenance of central sensitization in several rodent models of chronic pain. The present study aims to elucidate the IL-6 mediated neurological adaptation in dorsal horn in the rat with monosodium iodoacetate (MIA) - induced OA. Significant upregulation of IL-6 expression was detected in the dorsal horn in the modeled rats. Blockade of IL-6 function by tocilizumab markedly suppressed the activation of astrocytes and microglia in the ipsilateral dorsal horn, reduced c-Fos immunoreactivity in dorsal horn neurons, and attenuated the upregulation of glutamate receptor subunits GluR1 and NR2B in dorsal horn in the rats with MIA-induced OA. It was further reported that administration of tocilizumab significantly improved the performance in weight-bearing test and mitigated the mechanical allodynia in the modeled rats. These data illustrated spinal IL-6 mediated mechanism underlying the chronic pain, and proposed the potential therapeutic effect of tocilizumab on the chronic pain in the setting of OA.
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Conducta Animal/efectos de los fármacos , Interleucina-6/antagonistas & inhibidores , Osteoartritis/complicaciones , Dolor/etiología , Dolor/metabolismo , Asta Dorsal de la Médula Espinal/efectos de los fármacos , Asta Dorsal de la Médula Espinal/metabolismo , Animales , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Interleucina-6/metabolismo , Masculino , Dolor/tratamiento farmacológico , Dolor/fisiopatología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Asta Dorsal de la Médula Espinal/fisiopatología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Fructose-1, 6-bisphosphate aldolase (FBA) is a key plant enzyme that is involved in glycolysis, gluconeogenesis, and the Calvin cycle. It plays significant roles in biotic and abiotic stress responses, as well as in regulating growth and development processes. In the present paper, 21 genes encoding TaFBA isoenzymes were identified, characterized, and categorized into three groups: class I chloroplast/plastid FBA (CpFBA), class I cytosol FBA (cFBA), and class II chloroplast/plastid FBA. By using a prediction online database and genomic PCR analysis of Chinese Spring nulli-tetrasomic lines, we have confirmed the chromosomal location of these genes in 12 chromosomes of four homologous groups. Sequence and genomic structure analysis revealed the high identity of the allelic TaFBA genes and the origin of different TaFBA genes. Numerous putative environment stimulus-responsive cis-elements have been identified in 1,500-bp regions of TaFBA gene promoters, of which the most abundant are the light-regulated elements (LREs). Phylogenetic reconstruction using the deduced protein sequence of 245 FBA genes indicated an independent evolutionary pathway for the class I and class II groups. Although, earlier studies have indicated that class II FBA only occurs in prokaryote and fungi, our results have demonstrated that a few class II CpFBAs exist in wheat and other closely related species. Class I TaFBA was predicted to be tetramers and class II to be dimers. Gene expression analysis based on microarray and transcriptome databases suggested the distinct role of TaFBAs in different tissues and developmental stages. The TaFBA 4-9 genes were highly expressed in leaves and might play important roles in wheat development. The differential expression patterns of the TaFBA genes in light/dark and a few abiotic stress conditions were also analyzed. The results suggested that LRE cis-elements of TaFBA gene promoters were not directly related to light responses. Most TaFBA genes had higher expression levels in the roots than in the shoots when under various stresses. Class I cytosol TaFBA genes, particularly TaFBA10/12/18 and TaFBA13/16, and three class II TaFBA genes are involved in responses to various abiotic stresses. Class I CpFBA genes in wheat are apparently sensitive to different stress conditions.