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Glandular secretory trichomes (GSTs) can secrete and store a variety of specific metabolites. By increasing GST density, valuable metabolites can be enhanced in terms of productivity. However, the comprehensive and detailed regulatory network of GST initiation still needs further investigation. By screening a complementary DNA library derived from young leaves of Artemisia annua, we identified a MADS-box transcription factor, AaSEPALLATA1 (AaSEP1), that positively regulates GST initiation. Overexpression of AaSEP1 in A. annua substantially increased GST density and artemisinin content. The HOMEODOMAIN PROTEIN 1 (AaHD1)-AaMYB16 regulatory network regulates GST initiation via the jasmonate (JA) signaling pathway. In this study, AaSEP1 enhanced the function of AaHD1 activation on downstream GST initiation gene GLANDULAR TRICHOME-SPECIFIC WRKY 2 (AaGSW2) through interaction with AaMYB16. Moreover, AaSEP1 interacted with the JA ZIM-domain 8 (AaJAZ8) and served as an important factor in JA-mediated GST initiation. We also found that AaSEP1 interacted with CONSTITUTIVE PHOTOMORPHOGENIC 1 (AaCOP1), a major repressor of light signaling. In this study, we identified a MADS-box transcription factor that is induced by JA and light signaling and that promotes the initiation of GST in A. annua.
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Artemisia annua , Tricomas , Tricomas/genética , Tricomas/metabolismo , Artemisia annua/genética , Artemisia annua/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ciclopentanos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
For years, the paths of sequencing technologies and mass spectrometry have occurred in isolation, with each developing its own unique culture and expertise. These two technologies are crucial for inspecting complementary aspects of the molecular phenotype across the central dogma. Integrative multiomics strives to bridge the analysis gap among different fields to complete more comprehensive mechanisms of life events and diseases. Proteogenomics is one integrated multiomics field. Here in this review, we mainly summarize and discuss three aspects: workflow of proteogenomics, proteogenomics applications in cancer research, and the SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis of proteogenomics in cancer research. In conclusion, proteogenomics has a promising future as it clarifies the functional consequences of many unannotated genomic abnormalities or noncanonical variants and identifies driver genes and novel therapeutic targets across cancers, which would substantially accelerate the development of precision oncology.
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Vegetative propagation (VP) is an important practice for production in many horticultural plants. Sugar supply constitutes the basis of VP in bulb flowers, but the underlying molecular basis remains elusive. By performing a combined sequencing technologies coupled with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry approach for metabolic analyses, we compared two Lycoris species with contrasting regeneration rates: high-regeneration Lycoris sprengeri and low-regeneration Lycoris aurea. A comprehensive multi-omics analyses identified both expected processes involving carbohydrate metabolism and transcription factor networks, as well as the metabolic characteristics for each developmental stage. A higher abundance of the differentially expressed genes including those encoding ethylene responsive factors was detected at bulblet initiation stage compared to the late stage of bulblet development. High hexose-to-sucrose ratio correlated to bulblet formation across all the species examined, indicating its role in the VP process in Lycoris bulb. Importantly, a clear difference between cell wall invertase (CWIN)-catalyzed sucrose unloading in high-regeneration species and the sucrose synthase-catalyzed pathway in low-regeneration species was observed at the bulblet initiation stage, which was supported by findings from carboxyfluorescein tracing and quantitative real-time PCR analyses. Collectively, the findings indicate a sugar-mediated model of the regulation of VP in which high CWIN expression or activity may promote bulblet initiation via enhancing apoplasmic unloading of sucrose or sugar signals, whereas the subsequent high ratio of hexose-to-sucrose likely supports cell division characterized in the next phase of bulblet formation.
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Lycoris , Transcriptoma , Metabolismo de los Hidratos de Carbono/genética , Etilenos , Lycoris/genética , Lycoris/metabolismo , Metaboloma , Sacarosa/metabolismo , Factores de Transcripción/metabolismo , beta-Fructofuranosidasa/metabolismoRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is a major health concern worldwide, and the incidence of metabolic disorders associated with NAFLD is rapidly increasing because of the obesity epidemic. There are currently no approved drugs that prevent or treat NAFLD. Recent evidence shows that bavachin, a flavonoid isolated from the seeds and fruits of Psoralea corylifolia L., increases the transcriptional activity of PPARγ and insulin sensitivity during preadipocyte differentiation, but the effect of bavachin on glucose and lipid metabolism remains unclear. In the current study we investigated the effects of bavachin on obesity-associated NAFLD in vivo and in vitro. In mouse primary hepatocytes and Huh7 cells, treatment with bavachin (20 µM) significantly suppressed PA/OA or high glucose/high insulin-induced increases in the expression of fatty acid synthesis-related genes and the number and size of lipid droplets. Furthermore, bavachin treatment markedly elevated the phosphorylation levels of AKT and GSK-3ß, improving the insulin signaling activity in the cells. In HFD-induced obese mice, administration of bavachin (30 mg/kg, i.p. every other day for 8 weeks) efficiently attenuated the increases in body weight, liver weight, blood glucose, and liver and serum triglyceride contents. Moreover, bavachin administration significantly alleviated hepatic inflammation and ameliorated HFD-induced glucose intolerance and insulin resistance. We demonstrated that bavachin protected against HFD-induced obesity by inducing fat thermogenesis and browning subcutaneous white adipose tissue (subWAT). We revealed that bavachin repressed the expression of lipid synthesis genes in the liver of obese mice, while promoting the expression of thermogenesis, browning, and mitochondrial respiration-related genes in subWAT and brown adipose tissue (BAT) in the mice. In conclusion, bavachin attenuates hepatic steatosis and obesity by repressing de novo lipogenesis, inducing fat thermogenesis and browning subWAT, suggesting that bavachin is a potential drug for NAFLD therapy.
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Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ratones Obesos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hígado/metabolismo , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/genética , Flavonoides/farmacología , Dieta , Glucosa/metabolismo , Insulina/metabolismo , Dieta Alta en Grasa , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Sebaceous adenocarcinoma (SAC) mostly occurs in the elderly, and SAC in young and middle-aged population is inadequately investigated. OBJECTIVE: To explore the clinical features and prognosis of young and middle-aged adults with SAC. MATERIALS AND METHODS: Patients with skin SAC between ages 18 and 59 years from the Surveillance, Epidemiology, and End Results database (1975-2016) were eligible for this study. RESULTS: Seven hundred thirty-nine cases were identified. The proportion of extraocular SAC in the nonelderly increased from 1975-2005 to 2006-2016 ( p = .001), male predominance was observed in overall patients whereas female predominance in Asian population, and young patients had more head and neck SAC than middle-aged patients ( p = .014). The prognosis of young patients was better than middle-aged patients ( p = .004). Other independent prognostic factors included sex, marital status, tumor size, surgery, chemotherapy, and multiple primary cancer history. CONCLUSION: An increasing proportion of extraocular SAC was observed in young and middle-aged patients, and the young developed more head and neck SAC than the middle-aged. Female predominance was found in Asian population, and female patients had better prognosis. Younger age and married status indicated better prognosis, and around 20% of young and middle-aged patients might have poorer survival because of Muir-Torre syndrome.
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Adenocarcinoma Sebáceo , Síndrome de Muir-Torre , Neoplasias de las Glándulas Sebáceas , Adenocarcinoma Sebáceo/patología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de las Glándulas Sebáceas/epidemiología , Neoplasias de las Glándulas Sebáceas/patología , Neoplasias de las Glándulas Sebáceas/terapia , Piel/patología , Adulto JovenRESUMEN
Cold acclimation (CA) is a well-known strategy employed by plants to enhance freezing tolerance (FT) in winter. Global warming could disturb CA and increase the potential for winter freeze-injury. Thus, developing robust FT through complete CA is essential. To explore the molecular mechanisms of CA in woody perennials, we compared field and artificial CAs. Transcriptomic data showed that photosynthesis/photoprotection and fatty acid metabolism pathways were specifically enriched in field CA; carbohydrate metabolism, secondary metabolism and circadian rhythm pathways were commonly enriched in both field and artificial CAs. When compared with plants in vegetative growth in the chamber, we found that the light signals with warm air temperatures in the fall might induce the accumulation of leaf abscisic acid (ABA) and jasmonic acid (JA) concentrations, and activate Ca2+ , ABA and JA signaling transductions in plants. With the gradual cooling occurrence in winter, more accumulation of anthocyanin, chlorophyll degradation, closure/degradation of photosystem II reaction centers, and substantial accumulation of glucose and fructose contributed to obtaining robust FT during field CA. Moreover, we observed that in Rhododendron 'Elsie Lee', ABA and JA decreased in winter, which may be due to the strong requirement of zeaxanthin for rapid thermal dissipation and unsaturated fatty acids for membrane fluidity. Taken together, our results indicate that artificial CA has limitations to understand the field CA and field light signals (like short photoperiod, light intensity and/or light quality) before the low temperature in fall might be essential for complete CA.
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Perfilación de la Expresión Génica , Rhododendron/metabolismo , Aclimatación , Antocianinas/metabolismo , Carotenoides/metabolismo , Congelación , Genes de Plantas/fisiología , Ácido Linoleico/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/fisiología , Rhododendron/fisiología , Estrés Fisiológico , Ácido alfa-Linolénico/metabolismoRESUMEN
The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.
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Cadmio/metabolismo , Proteínas de Transporte de Catión/genética , Selenio/metabolismo , Transporte Biológico , Proteínas de Transporte de Catión/metabolismo , Bases de Datos Genéticas , Enfermedad/genética , Células HeLa , Homeostasis , Humanos , Hierro/metabolismo , Manganeso/metabolismo , Polimorfismo de Nucleótido Simple/genética , Zinc/metabolismoRESUMEN
The design and synthesis of metal-organic frameworks (MOFs) enclosed with multiple catalytic active sites is favorable for cooperative catalysis, but is is still challenging. Herein, we developed a sequential postsynthetic ionization and metalation strategy to prepare bifunctional multivariate Zr-MOFs incorporating zinc porphyrin and imidazolium functionalities. Using this facile strategy, tetratopic [5,10,15,20-tetrakis(4-carboxyphenyl)porphyrinato]zinc(II) (ZnTCPP) ligands were successfully installed into the cationic Zr-MOF to obtain ZnTCPPâ(Br-)Etim-UiO-66. These MTV-MOFs, including TCPPâIm-UiO-66, TCPPâ(Br-)Etim-UiO-66, and ZnTCPPâ(Br-)Etim-UiO-66, were well characterized and used in CO2 capture and conversion into cyclic carbonate from allyl glycidyl ether and CO2 under cocatalyst-free and 1 bar CO2 pressure conditions. It was found that the structural features and CO2 affinity properties of these MTV-MOFs can be tuned by introducing imidazolium groups or doping zinc sites. Additionally, ZnTCPPâ(Br-)Etim-UiO-66 exhibited enhanced catalytic activities compared to other MTV-MOFs herein for obtaining the 3-allyloxy-1,2-proplyene carbonate product, which was attributed to the cooperative effect of Zn2+ sites and Br- ions in this microporous ionic MTV-MOF. ZnTCPPâ(Br-)Etim-UiO-66 can be recycled easily and used at least three times.
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Tumor angiogenesis is mediated by vascular endothelial growth factor receptor (VEGFR) and other protein kinases. Inhibition of these kinases presents an attractive approach for developing anticancer therapeutics. In this work, a series of 2,5,7-trisubstituted oxazolo[5,4-d]pyrimidines were synthesized, and their inhibitory activities were investigated against VEGFR-2 and human umbilical vein endothelial cells (HUVEC) in vitro. Compound 9n exhibited the most potent inhibitory activity with IC50 values of 0.33 and 0.29â µM for VEGFR-2â kinase and HUVEC, respectively. A further kinase selectivity assay revealed that these compounds exhibit good VEGFR and moderate EGFR inhibitory activities. Docking analysis suggested a common mode of interaction at the ATP-binding site of VEGFR-2.
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Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adenosina Trifosfato/metabolismo , Sitios de Unión , Proliferación Celular/efectos de los fármacos , Técnicas de Química Sintética , Evaluación Preclínica de Medicamentos/métodos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Pirimidinas/química , Relación Estructura-Actividad , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The prostate-specific antigen (PSA) test contributes a lot to the diagnosis and treatment of prostate cancer (PCa) and, along with imaging-guided prostate biopsy, has improved the diagnosis rate of lower-risk PCa and the accuracy of its clinical staging. However, many questions and controversies remain as to the choice of optimal biopsy strategies. Scholars differ in views about how to utilize PCa-related biomarkers to optimize the detection of initial and repeat biopsies. This review focuses on the present status of and advances in transrectal ultrasound-guided biopsy for PCa.
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Biopsia Guiada por Imagen/métodos , Próstata/patología , Neoplasias de la Próstata/patología , Humanos , Masculino , Antígeno Prostático Específico/sangre , Ultrasonografía Intervencional/métodosRESUMEN
OBJECTIVE: To investigate epidemiological characteristics of prevalence, impact factors and etiology on developmental delay of 18-month-old children from four districts/counties in Beijing. METHODS: An epidemiological study on developmental delay was designed to investigate all the 18-month-old children enrolled from Shunyi,Daxing,Miyun and Yanqing districts/counties in Beijing from May to September, 2011. Combining the tertiary network of child health with hospital clinical study was used. Child developmental questionnaires were completed by doctors in communities of the first network of child health. Gesell Developmental Schedules for children with Denver developmental screening test (DDST) screening positive results were assessed by doctors in districts/counties hospitals of the second network of child health. The children diagnosed as developmental delay were transferred to the tertiary hospitals of the third network of child health for further etiological diagnosis, follow-up and developmental evaluation. The case-control study compared between children with/without developmental delay were performed in accordance with the 1:4 ratios by gender and residence community matched. SPSS 16.0 was adopted for data analysis of the case-control study. RESULTS: A total of 3 182 children were screened among the 4 037 children fitting the criteria,and the coverage rate was 78.8% (3 182/4 037). Of the 3 182 screened children, 22 children were diagnosed as developmental delay. The prevalence rate was 6.91 (22/3 182). Out of the 22 children with developmental delay, 15 were boys and 7 were girls. The sex ratio was 2.1:1. The prevalence rates of the children with developmental delay in Shunyi, Daxing, Miyun and Yanqing were 3.45 (4/1 160), 4.50 (5/1 111), 15.87 (7/441) and 12.77 (6/479), respectively. The results from one-way ANOVA analysis showed the main risk factors in children with developmental delay included low-income families, mothers' low educational level, small size for gestational age infant, multiple fetuses, serious diseases after birth, congenital malformations and physical retardation (P<0.05). CONCLUSION: The screening coverage rate of this study is 78.8%. The prevalence rate of children with developmental delay is 6.91 , which is significantly different in sex ratio and districts of the subjects. The etiology of developmental delay might be associated with social-economic and biological factors.
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Discapacidades del Desarrollo/epidemiología , China/epidemiología , Discapacidades del Desarrollo/etiología , Femenino , Humanos , Lactante , Masculino , Tamizaje Masivo , Prevalencia , Factores de Riesgo , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
Bone cancer pain is difficult to treat and has a strong impact on the quality of life of patients. Few therapies have emerged because the molecular mechanisms underlying bone cancer pain are poorly understood. Recently, T-cell death-associated gene 8 (TDAG8) has been shown to participate in complete Freund's adjuvant-induced chronic inflammatory pain. In this study, we aimed to examine whether TDAG8 and its downstream protein kinase A (PKA) pathway are involved in bone cancer pain. A bone cancer pain model was made by inoculation of Walker 256 cells into the intramedullary space of rat tibia. Spinal TDAG8 expression was increased after inoculation with tumor cells. Intrathecal TDAG8 siRNA attenuated bone cancer pain behaviors during the initiation and maintenance phases; there were also concomitant decreases in TDAG8 mRNA and protein levels in spinal cord. Moreover, we found spinal PKA and phosphorylated cAMP response element-binding (pCREB) protein levels were up-regulated in the rat model of bone cancer pain. Knockdown of TDAG8 resulted in reduced bone cancer pain-induced spinal PKA and pCREB protein expression in two procedures. Furthermore, intrathecal H-89 (a PKA inhibitor) significantly attenuated bone cancer pain behaviors in rats. Our results suggest a causal relationship between TDAG8 expression and the initiation and maintenance of bone cancer pain. Activation of spinal TDAG8 contributes to bone cancer pain through the PKA signaling pathway in rats. These findings may lead to novel strategies for the treatment of bone cancer pain.
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Neoplasias Óseas/complicaciones , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Dolor/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Carcinoma 256 de Walker , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Femenino , Isoquinolinas/farmacología , Trasplante de Neoplasias , Dolor/enzimología , Dolor/etiología , Células del Asta Posterior/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , ARN Interferente Pequeño , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Sulfonamidas/farmacología , Regulación hacia ArribaRESUMEN
Previous studies have suggested that the release of brain-derived neurotrophic factor (BDNF) from microglia in spinal cord is necessary for maintaining pain hypersensitivity after nerve injury. However, little is known about its role in cancer-induced bone pain (CIBP), which is in some ways unique. This study demonstrates a critical role of minocycline (a potent inhibitor of microglial activation)-modulated BDNF in the induction and maintenance of behavioral hypersensitivity in a rat model of CIBP. We assessed mechanical threshold and spontaneous pain of CIBP rats. Moreover, minocycline was administered intrathecally from day 4 to day 6 (early stage) or from day 10 to day 12 (later stage), after carcinoma cell inoculation. Real-time PCR, Western blots, and double immunofluorescence were used to detect the expression of OX-42 (marker of activated microglia), phosphorylated p38-MAPK (p-p38), and BDNF. We found that intrathecal minocycline could prevent CIBP at an early stage of tumor growth (from day 4 to day 6). However, at the late stage (from day 10 to day 12), intrathecal minocycline had no effect. Moreover, the expression of OX-42 and BDNF under CIBP, peaking on day 6, were all reduced after minocycline injection from day 4 to day 6. The ability of minocycline-induced reduction of BDNF in the induction of behavioral hypersensitivity could provide an opportunity for alleviating CIBP.
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Antibacterianos/uso terapéutico , Neoplasias Óseas/complicaciones , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Minociclina/uso terapéutico , Umbral del Dolor/efectos de los fármacos , Dolor/tratamiento farmacológico , Médula Espinal/efectos de los fármacos , Animales , Antibacterianos/farmacología , Conducta Animal/efectos de los fármacos , Neoplasias Óseas/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/farmacología , Femenino , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Minociclina/farmacología , Dolor/etiología , Dolor/metabolismo , Dimensión del Dolor , Fosforilación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Médula Espinal/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Brain-derived neurotrophic factor (BDNF) released within the spinal cord induces phosphorylation of N-methyl-D-aspartate (NMDA) receptors on the spinal cord neurons. This process is necessary for maintaining pain hypersensitivity after nerve injury. However, little is known about the role of BDNF and NMDA receptors in cancer-induced bone pain (CIBP), whose features are unique. This study demonstrates a critical role of the BDNF-modulated NMDA subunit 1 (NR1) in the induction and maintenance of behavioral hypersensitivity in a rat model of CIBP, both in the spinal cord and in the dorsal root ganglia (DRG). We selectively suppressed BDNF expression by RNA interference (RNAi) using intrathecal administration of BDNF small interfering RNA (siRNA). Then, we assessed mechanical threshold and spontaneous pain in CIBP rats. Real-time PCR, Western blotting, and fluorescent immunohistochemical staining were used to detect BDNF or NR1 both in vivo and in vitro. BDNF and phospho-NR1 were expressed under CIBP experimental conditions, with expression levels peaking at day 6 (BDNF) or 9 (NR1). Intrathecal BDNF siRNA prevented CIBP at an early stage of tumor growth (days 4-6). However, at later stages (days 10-12), intrathecal BDNF siRNA only attenuated, but did not completely block, the established CIBP. BDNF-induced NMDA receptor activation in the spinal cord or DRG leads to central sensitization and behavioral hypersensitivity. Thus, BDNF might provide a targeting opportunity for alleviating CIBP.
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Neoplasias Óseas/complicaciones , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Dolor/etiología , Receptores de N-Metil-D-Aspartato/metabolismo , Dolor Abdominal/tratamiento farmacológico , Dolor Abdominal/etiología , Análisis de Varianza , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Modelos Animales de Enfermedad , Femenino , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/etiología , Microglía/efectos de los fármacos , Microglía/metabolismo , Dolor/tratamiento farmacológico , Dolor/metabolismo , Dolor/patología , ARN Mensajero/metabolismo , ARN Interferente Pequeño/uso terapéutico , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Médula Espinal/patología , Factores de TiempoRESUMEN
Breast cancer is the most common malignancy in women, and many breast cancer patients fail conventional treatment strategies of chemotherapy, radiation, and antiestrogen therapy. Research into the molecular pathways and biomarkers involved in the development of breast cancer should yield information that will guide therapeutic decisions. Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are involved in the carcinogenesis of breast cancer and exist tight crosstalk with estrogen receptor (ER) pathway. Combination of EGFR and COX-2 inhibitors, therefore, could be an effective strategy for reducing cell growth in estrogen-dependent breast cancer. In order to verify the effects of EGFR and COX-2 inhibitors, breast cancer cells MCF-7 and SKBR-3 were characterized for receptors status and then treated with respective inhibitors (nimotuzumab and celecoxib) alone and in combination. Both cell lines were sensitive to celecoxib, but not to nimotuzumab. However, combination of two drugs demonstrated synergistic effects on cell killing. Moreover, association of two drugs resulted in SKBR-3 cells, a further G0/G1 phase arrest than one drug alone. Downregulation of p-EGFR, p-Akt, p-mTOR, and amplified in breast cancer 1 (AIB1) were observed in both cell lines, and upregulation of E-cadherin was only found in MCF-7, after treatment with single agent or in combination. These studies suggest that nimotuzumab and celecoxib exert synergistic antiproliferation effects in breast cancer, which partly correlates with ER status. Due to Akt/mTOR, EMT and AIB1 pathways participate in this process, therefore, E-cadherin and AIB1 may be considered as possible biomarkers to predict response in ER-positive breast cancer cells treated with EGFR and COX-2 inhibitors.
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Anticuerpos Monoclonales Humanizados/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Pirazoles/farmacología , Sulfonamidas/farmacología , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/efectos de los fármacos , Western Blotting , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cadherinas/metabolismo , Celecoxib , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/farmacología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Receptores ErbB/metabolismo , Estrógenos/metabolismo , Femenino , Citometría de Flujo , Fase G1/efectos de los fármacos , Humanos , Coactivador 3 de Receptor Nuclear/metabolismo , Pirazoles/administración & dosificación , Receptores de Estrógenos/metabolismo , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Sulfonamidas/administración & dosificación , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
INTRODUCTION: It is unknown whether dressings reduce the risk of SSI after clean and clean-contaminated surgery. OBJECTIVE: This meta-analysis was conducted to assess the outcomes of immediate air exposure of surgical sites after primary closure. MATERIALS AND METHODS: A systematic search of Embase, PubMed, and Web of Science from the time of database establishment through October 2021 was performed. The SSI incidence and other surgical wound-associated events were extracted and their effect sizes calculated. RESULTS: Six RCTs with a total of 1243 surgery cases (1228 non-contaminated, 15 contaminated) were included. SSI incidence of 11% and 11.1% was observed for immediate air exposure and dressings, respectively, when pooled irrespective of surgery type (RR, 0.95; 95% CI, 0.68-1.33 [P = .76]). Subgroup analysis showed similar SSI incidence between air exposure and dressings following clean (P = .39) and clean-contaminated surgery (P = .64). Neither gauze dressings (P = .65), film dressings (P = .07), nor tissue glue-as-a-dressing (P = .94) use resulted in significantly lower SSI incidence than air exposure. CONCLUSIONS: This meta-analysis shows that dressings (gauze dressings, film dressings, and tissue glue-as-a-dressing) do not outperform immediate air exposure in terms of SSI occurrence following primary closure of clean and clean-contaminated surgical wounds.
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Herida Quirúrgica , Adhesivos Tisulares , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Cicatrización de Heridas , Ensayos Clínicos Controlados Aleatorios como Asunto , VendajesRESUMEN
We examined the dynamics of community structure in forests formed after cutting all Phyllostachys edulis at altitude of 480, 580, 700 and 800 m of the Mount Tianmu National Nature Reserve in Zhejiang Province, from 2017 to 2020, using phytocommunity method. Results showed that the total number of plant individuals was 515 belonging to 50 species, 43 genera and 27 families in 2017. After three years, 30 new plant species emerged, belonging to 23 genera and 14 families, and the number of individuals increased by 116.9% in 2020. The new species were mainly P. edulis, Callicarpa bodinieri, Lindera glauca, Litsea cubeba and Broussonetia papyrifera, which primarily distributed at the altitude of 580 and 700 m. The tree species with the largest importance value in the communities at altitude of 580, 700 and 800 m remained stable, including Cunninghamia lanceolata, Ailanthus altis-sima and Liquidambar formosana, whereas that in community at altitude of 480 m changed from C. lanceolata to Camellia oleifera. Meanwhile, the diameter distributions of community significantly differed across different altitudes. The diameter distribution of the community at altitude of 480 m displayed a single peak left skewness from the reverse 'J' type, whilst that at altitude of 700 m developed from a reverse 'J' type to an exponential type. The diameter distribution in the community at altitude of 800 m followed a normal pattern and the peak value shifted from 24 to 30 cm. Both the Simpson dominance index and Shannon diversity index of the four communities increased across the three years, and all decreased significantly with the increase of altitude. Meanwhile, ß diversity increased with rising altitude and increasing distance among altitudes. The recruitment of new species in 2020 provided sufficient seedlings and saplings for natural regeneration, but it had not yet succeeded to the subtropical climax community.
Asunto(s)
Altitud , Poaceae , Humanos , Árboles , Bosques , ChinaRESUMEN
Cold acclimation (CA) and deacclimation (DA), which are often accompanied by changes in freezing tolerance (FT), carbohydrates and hormones, are crucial for winter survival, especially under global warming. Plants with weak CA and premature DA caused by warm winters and/or unseasonal warm spells can be easily injured by adverse reactions to cold. Thus, understanding the molecular mechanisms of FT is imperative. In this study, we used high-throughput RNA-seq to profile the CA and DA of leaves of overwintering Rhododendron "Miyo-no-Sakae" over time; these leaves do not undergo dormancy but do undergo photoprotection during CA, and they do not grow during DA. Using Mfuzz and weighted gene coexpression network analysis, we identified specific transcriptional characteristics in each phase of CA and DA and proposed networks involving coexpressed genes and physiological traits. In particular, we discovered that the circadian rhythm is critical for obtaining the strongest FT, and high expression of circadian rhythm-related genes might be linked to sugar accumulation during winter. Furthermore, evergreen leaves exhibited robust photoprotection during winter, as revealed by high values of nonphotochemical quenching, high expression of transcripts annotated as "early light-induced proteins", loss of granum stacks and destacking of thylakoids, all of which were alleviated during DA. The strong requirement of photoprotection could be the reason for decreased abscisic acid (ABA) and jasmonic acid (JA) contents during CA, and decreases in ABA and JA contents may contribute to decreases in lignin content. Our data suggest that the molecular mechanisms of FT in overwintering leaves are unique, which may be due to the high requirements for photoprotection during winter.
RESUMEN
The plant Artemisia annua is well known for its production of artemisinin, a sesquiterpene lactone that is an effective antimalarial compound. Although remarkable progress has been made toward understanding artemisinin biosynthesis, the effect of MADS-box family transcription factors on artemisinin biosynthesis is still poorly understood. In this study, we identified a MADS transcription factor, AaSEP4, that was predominantly expressed in trichome. AaSEP4 acts as a nuclear-localized transcriptional activator activating the expression of AaGSW1 (GLANDULAR TRICHOME-SPECIFIC WRKY1). Dual-luciferase and Yeast one-hybrid assays revealed that AaSEP4 directly bound to the CArG motif in the promoter region of AaGSW1. Overexpression of AaSEP4 in A. annua significantly induced the expression of AaGSW1 and four artemisinin biosynthesis genes, including amorpha-4,11-diene synthase (ADS), cytochrome P450 monooxygenase (CYP71AV1), double-bond reductase 2 (DBR2) and aldehyde dehydrogenase 1 (ALDH1). Furthermore, the results of high-performance liquid chromatography (HPLC) showed that the artemisinin content was significantly increased in the AaSEP4-overexpressed plants. In addition, RT-qPCR results showed that AaSEP4 was induced by methyl jasmonic acid (MeJA) treatment. Taken together, these results explicitly demonstrate that AaSEP4 is a positive regulator of artemisinin biosynthesis, which can be used in the development of high-artemisinin yielding A. annua varieties.