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WRN helicase is a promising target for treatment of cancers with microsatellite instability (MSI) due to its essential role in resolving deleterious non-canonical DNA structures that accumulate in cells with faulty mismatch repair mechanisms1-5. Currently there are no approved drugs directly targeting human DNA or RNA helicases, in part owing to the challenging nature of developing potent and selective compounds to this class of proteins. Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214. This compound selectively engages a cysteine (C727) located in a region of the helicase domain subject to interdomain movement during DNA unwinding. VVD-133214 binds WRN protein cooperatively with nucleotide and stabilizes compact conformations lacking the dynamic flexibility necessary for proper helicase function, resulting in widespread double-stranded DNA breaks, nuclear swelling and cell death in MSI-high (MSI-H), but not in microsatellite-stable, cells. The compound was well tolerated in mice and led to robust tumour regression in multiple MSI-H colorectal cancer cell lines and patient-derived xenograft models. Our work shows an allosteric approach for inhibition of WRN function that circumvents competition from an endogenous ATP cofactor in cancer cells, and designates VVD-133214 as a promising drug candidate for patients with MSI-H cancers.
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Regulación Alostérica , Descubrimiento de Drogas , Inhibidores Enzimáticos , Proteómica , Helicasa del Síndrome de Werner , Animales , Femenino , Humanos , Masculino , Ratones , Regulación Alostérica/efectos de los fármacos , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Cisteína/efectos de los fármacos , Cisteína/metabolismo , Roturas del ADN de Doble Cadena/efectos de los fármacos , Descubrimiento de Drogas/métodos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inestabilidad de Microsatélites , Modelos Moleculares , Helicasa del Síndrome de Werner/antagonistas & inhibidores , Helicasa del Síndrome de Werner/química , Helicasa del Síndrome de Werner/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Muerte Celular/efectos de los fármacos , Adenosina Trifosfato/metabolismoRESUMEN
The study investigates the therapeutic effects and mechanisms of ginsenoside Rg_1(GRg_1) on sepsis-induced acute lung injury(SALI). A murine model of SALI was created using cecal ligation and puncture(CLP) surgery, and mice were randomly assigned to groups for GRg_1 intervention. Survival and body weight changes were recorded, lung function was assessed with a non-invasive lung function test system, and lung tissue damage was evaluated through HE staining. The content and expression of inflammatory factors were measured by ELISA and qRT-PCR. Apoptosis was examined using flow cytometry and TUNEL staining. The activation and expression of apoptosis-related molecules cysteinyl aspartate specific proteinase 3(caspase-3), B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein(Bax), and endoplasmic reticulum stress-related molecules protein kinase R-like endoplasmic reticulum kinase(PERK), eukaryotic initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), and C/EBP homologous protein(CHOP) were studied using Western blot and qRT-PCR. In addition, an in vitro model of lipopolysaccharide(LPS)-induced lung alveolar epithelial cell injury was used, with the application of the endoplasmic reticulum stress inducer tunicamycin to validate the action mechanism of GRg_1. RESULTS:: indicated that, when compared to the model group, GRg_1 intervention significantly enhanced the survival time of CLP mice, mitigated body weight loss, and improved impaired lung function indices. The GRg_1-treated mice also displayed reduced lung tissue pathological scores, a reduced lung tissue wet-to-dry weight ratio, and lower protein content in the bronchoalveolar lavage fluid. Serum levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α), as well as the mRNA expressions of these cytokines in lung tissues, were decreased. There was a notable decrease in the proportion of apopto-tic alveolar epithelial cells, and down-regulated expressions of caspase-3, Bax, PERK, eIF2α, ATF4, and CHOP and up-regulated expression of Bcl-2 were observed. In vitro findings showed that the apoptosis-lowering and apoptosis-related protein down-regulating effects of GRg_1 were significantly inhibited with the co-application of tunicamycin. Altogether, GRg_1 reduces apoptosis of alveolar epithelial cells, inhibits inflammation in the lungs, alleviates lung injury, and enhances lung function, possibly through the PERK/eIF2α/ATF4/CHOP pathway.
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Factor de Transcripción Activador 4 , Lesión Pulmonar Aguda , Células Epiteliales Alveolares , Apoptosis , Factor 2 Eucariótico de Iniciación , Ginsenósidos , Sepsis , Factor de Transcripción CHOP , eIF-2 Quinasa , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/genética , Ginsenósidos/farmacología , Factor de Transcripción Activador 4/metabolismo , Factor de Transcripción Activador 4/genética , Ratones , Apoptosis/efectos de los fármacos , Factor de Transcripción CHOP/metabolismo , Factor de Transcripción CHOP/genética , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/metabolismo , Sepsis/genética , eIF-2 Quinasa/metabolismo , eIF-2 Quinasa/genética , Factor 2 Eucariótico de Iniciación/metabolismo , Factor 2 Eucariótico de Iniciación/genética , Masculino , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/metabolismo , Humanos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
Chemokine CXCL4L1, a homologue of CXCL4, is a more potent antiangiogenic ligand. Its structural property is correlated with the downstream receptor binding. The two chemokines execute their functions by binding the receptors of CXCR3A and CXCR3B. The receptors differ by an extra 51-residue extension in the CXCR3B N-terminus. To understand the binding specificity, a GB1 protein scaffold was used to carry different CXCR3 extracellular elements, and artificial CXCL4 and CXCL4L1 monomers were engineered for the binding assay. We first characterized the molten globule property of CXCL4L1. The structural property causes the CXCL4L1 tetramer to dissociate into monomers in low concentrations, but native CXCL4 adopts a stable tetramer structure in solution. In the titration experiments, the combination of the CXCR3A N-terminus and receptor extracellular loop 2 provided moderate and comparable binding affinities to CXCL4 and CXCL4L1, while sulfation on the CXCR3A N-terminal tyrosine residues provided binding specificity. However, the CXCR3B N-terminal extension did not show significant enhancement in the binding of CXCL4 or CXCL4L1. This result indicates that the tendency to form a chemokine monomer and the binding affinity together contribute the high antiangiogenic activity of CXCL4L1.
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Quimiocinas , Factor Plaquetario 4 , Factor Plaquetario 4/química , Factor Plaquetario 4/metabolismo , Receptores CXCR3/químicaRESUMEN
BACKGROUND: The controversy surrounding Roux-en-Y (R-Y) and Billroth II with Braun (BII + B) reconstruction as an anti-bile reflux procedure after distal gastrectomy has persisted. Recent studies have demonstrated their efficacy, but the long-term outcomes and postoperative quality of life (QoL) among patients have yet to be evaluated. Therefore, we compared the short-term and long-term outcomes of the two procedures as well as QoL. METHODS: The clinical data of 151 patients who underwent total laparoscopic distal gastrectomy (TLDG) at the Gastrointestinal Surgery Department of the Second Hospital of Fujian Medical University from January 2016 to December 2019 were retrospectively analyzed. Of these, 57 cases with Roux-en-Y procedure (R-Y group) and 94 cases with Billroth II with Braun procedure were included (BII + B group). Operative and postoperative conditions, early and late complications, endoscopic outcomes at year 1 and year 3 after surgery, nutritional indicators, and quality of life scores at year 3 postoperatively were compared between the two groups. RESULTS: The R-Y group recorded a significantly longer operative time (194.65 ± 21.52 vs. 183.88 ± 18.02 min) and anastomotic time (36.96 ± 2.43 vs. 27.97 ± 3.74 min) compared to the BII + B group (p < 0.05). However, no other significant differences were observed in terms of perioperative variables, including blood loss (p > 0.05). Both groups showed comparable rates of early and late complications. Endoscopic findings indicated similar food residuals at years 1 and 3 post-surgery for both groups. The R-Y group had a lower occurrence of residual gastritis and bile reflux at year 1 and year 3 after surgery, with a statistically significant difference (p < 0.001). Reflux esophagitis was not significantly different between the R-Y and BII + B groups in year 1 after surgery (p = 0.820), but the R-Y group had a lower incidence than the BII + B group in year 3 after surgery (p = 0.023). Nutritional outcomes at 3 years after surgery did not differ significantly between the two groups (p > 0.05). Quality of life scores measured by the QLQ-C30 scale were not significantly different between the two groups. However, on the QLQ-STO22 scale, the reflux score was significantly lower in the R-Y group than in the BII + B group (0 [0, 0] vs. 5.56 [0, 11.11]) (p = 0.003). The rest of the scores were not significantly different (p > 0.05). CONCLUSION: Both R-Y and B II + B reconstructions are equally safe and efficient for TLDG. Nevertheless, the R-Y reconstruction reduces the incidence of residual gastritis, bile reflux, and reflux esophagitis, as well as postoperative reflux symptoms, and provides a better quality of life for patients. R-Y reconstruction is superior to BII + B reconstruction for TLDG.
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Reflujo Biliar , Esofagitis Péptica , Gastritis , Laparoscopía , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Calidad de Vida , Reflujo Biliar/epidemiología , Reflujo Biliar/etiología , Reflujo Biliar/cirugía , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/complicaciones , Gastroenterostomía/efectos adversos , Gastroenterostomía/métodos , Gastrectomía/efectos adversos , Gastrectomía/métodos , Anastomosis en-Y de Roux/efectos adversos , Anastomosis en-Y de Roux/métodos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Esofagitis Péptica/epidemiología , Esofagitis Péptica/etiología , Esofagitis Péptica/cirugía , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiologíaRESUMEN
BACKGROUND: To compare short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis for laparoscopic total gastrectomy. METHODS: This retrospective cohort study included patients with gastric cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to March 2020. Quality of life, intraoperative and postoperative conditions were analyzed. RESULTS: Compared with the conventional assisted group, the modified overlap group showed a shorter auxiliary incision, milder postoperative pain, shorter time to the first postoperative anal exhaust, shorter time to the first postoperative liquid food intake, and shorter postoperative stay. There were no differences between the two groups regarding operation time, esophagus-jejunum anastomosis time, intraoperative blood loss, number of lymph nodes dissected, and length of the upper incision margin. There were no differences between the two groups regarding postoperative early and late complications. There were no differences between the two groups regarding the QLQ-C30 scale three years after the operation. The scores of the QLQ-STO22 scale 3 years after the operation showed significantly lower scores for dysphagia and feeding limit in the modified overlap group than those in the conventional assisted anastomosis group. There was no recurrence in the modified overlap group but one patient in the conventional assisted group. CONCLUSIONS: Patients undergoing totally laparoscopic total gastrectomy with modified overlap anastomosis have better minimal invasiveness and faster post-operative recovery than conventional incision-assisted anastomosis.
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Laparoscopía , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Calidad de Vida , Laparoscopía/efectos adversos , Anastomosis Quirúrgica/efectos adversos , Gastrectomía/efectos adversos , Neoplasias Gástricas/patología , Resultado del Tratamiento , Complicaciones Posoperatorias/etiologíaRESUMEN
Mesenchymal stem cell (MSC) therapy is considered a new treatment for a wide range of diseases and injuries, but challenges remain, such as poor survival, homing and engraftment rates, thus limiting the therapeutic efficacy of the transplanted MSCs. Many strategies have been developed to enhance the therapeutic efficacy of MSCs, such as preconditioning, co-transplantation with graft materials and gene modification. Hepatocyte growth factor (HGF) is secreted by MSCs, which plays an important role in MSC therapy. It has been reported that the modification of the HGF gene is beneficial to the therapeutic efficacy of MSCs, including diseases of the heart, lung, liver, urinary system, bone and skin, lower limb ischaemia and immune-related diseases. This review focused on studies involving HGF/MSCs both in vitro and in vivo. The characteristics of HGF/MSCs were summarized, and the mechanisms of their improved therapeutic efficacy were analysed. Furthermore, some insights are provided for HGF/MSCs' clinical application based on our understanding of the HGF gene and MSC therapy.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Hepatocitos/metabolismo , Pulmón/metabolismo , Células Madre Mesenquimatosas/metabolismoRESUMEN
The midbody is a transient structure forming out of the central spindle at late telophase. Both the midbody and central spindle have important functions ensuring completion of cytokinesis and defects in this process may lead to genetic diseases, including cancer. Thus, understanding the mechanisms that control cytokinesis during mitosis can reveal the key components taking part in some of the processes that promote accurate cell division. Our previous study showed that overexpression of FLJ25439 causes cytokinesis defect with midbody arrest and induces tetraploids with prolonged cell growth/cell cycle progression (Pan et al., 2015). Here, we extend our investigation with regard to the expression profile/regulation and cellular localization/function of FLJ25439 during mitosis/cytokinesis. Using a monoclonal antibody 2A4 we found that FLJ25439 expression is cell cycle-dependent and subjected to APC/C complex regulation. Furthermore, it is a novel substrate for the APC/C-Cdc20 complex and its degradation is proteasome-dependent through D-box recognition during mitotic exit. Immunofluorescence microscopy showed it is distributed at the central spindle and midbody, two structures considered important for completion of cell division, in telophase and cytokinesis, respectively, during cell cycle progression. Depletion of FLJ25439 expression revealed defects in chromosome alignment/segregation and delayed mitosis/cytokinesis progression. We thus conclude that FLJ25439 is a hitherto undiscovered factor involved in cytokinesis regulation.
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Citocinesis , Huso Acromático , Anticuerpos Monoclonales/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Segregación Cromosómica , Mitosis , Complejo de la Endopetidasa Proteasomal/metabolismo , Huso Acromático/metabolismoRESUMEN
Pestalotiopsis species have gained attention thanks to their structurally complex and biologically active secondary metabolites. In past decades, several new secondary metabolites were isolated and identified. Their bioactivities were tested, including anticancer, antifungal, antibacterial, and nematicidal activity. Since the previous review published in 2014, new secondary metabolites were isolated and identified from Pestalotiopsis species and unidentified strains. This review gathered published articles from 2014 to 2021 and focused on 239 new secondary metabolites and their bioactivities. To date, 384 Pestalotiopsis species have been discovered in diverse ecological habitats, with the majority of them unstudied. Some may contain secondary metabolites with unique bioactivities that might benefit pharmacology.
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Antifúngicos , Pestalotiopsis , Antifúngicos/farmacología , EcosistemaRESUMEN
MAIN CONCLUSION: Overexpression of the leaf color (Lc) gene in Ma bamboo substantially increased the accumulation level of anthocyanin, and improved plant tolerance to cold and drought stresses, probably due to the increased antioxidant capacity. Most bamboos, including Ma bamboo (Dendrocalamus latiflorus Munro), are naturally evergreen and sensitive to cold and drought stresses, while it's nearly impossible to make improvements through conventual breeding due to their long and irregular flowering habit. Moreover, few studies have reported bamboo germplasm innovation through genetic engineering as bamboo genetic transformation remains difficult. In this study, we have upregulated anthocyanin biosynthesis in Ma bamboo, to generate non-green Ma bamboo with increased abiotic stress tolerance. By overexpressing the maize Lc gene, a bHLH transcription activator involved in the anthocyanin biosynthesis in Ma bamboo, we generated purple bamboos with increased anthocyanin levels including cyanidin-3-O-rutinoside, peonidin 3-O-rutinoside, and an unknown cyanidin pentaglycoside derivative. The expression levels of 9 anthocyanin biosynthesis genes were up-regulated. Overexpression of the Lc gene improved the plant tolerance to cold and drought stress, probably due to increased antioxidant capacity. The levels of the cold- and drought-related phytohormone jasmonic acid in the transgenic plants were also enhanced, which may also contribute to the plant stress-tolerant phenotypes. High anthocyanin accumulation level did not affect plant growth. Transcriptomic analysis showed higher expressions of genes involved in the flavonoid pathway in Lc transgenic bamboos compared with those in wild-type ones. The anthocyanin-rich bamboos generated here provide an example of ornamental and multiple agronomic trait improvements by genetic engineering in this important grass species.
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Sequías , Regulación de la Expresión Génica de las Plantas , Antocianinas , Respuesta al Choque por Frío , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismoRESUMEN
Room-temperature plasmonic-crystal lasers have been demonstrated with a square-lattice gold nano-pillar arrays on top of InGaAs/GaAs quamtum wells on a GaAs substrate. The lasing wavelength is tunable in the range of 865-1001â nm by varying the lattice period. The lasers exhibit an extremely narrow linewidth and small divergence angle so could have great potential for various applications. An unexpected mirror cavity effect has been observed and investigated. The mirror-cavity lasers have a very low threshold and could be developed to realize electrically-driven plasmonic lasers.
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OBJECTIVE: To assess the diagnostic value of Trefoil factor 3 (TFF3) and the correlation between TFF3 expression and clinicopathological features in patients with gastric cancer (GC). METHODS: PubMed, The Cochrane, EMbase, and Web of Science were retrieved comprehensively to collect relevant literature. The search ended on 31 May 2020. All data were analyzed using PubMed, The Cochrane, EMbase, and Web of Science were retrieved to collect relevant articles. All data from the included studies were subjected to meta-analysis using Stata 12.0 software. RESULTS: Seventeen studies involved 4654 subjects were included. For the diagnostic value of TFF3 for GC, the sensitivity, specificity, and AUC were 0.71, 0.80, and 0.80, respectively. For the clinicopathological value of TFF3, tissue TFF3 expression showed a higher risk of lymph node metastasis (OR 2.20, 95% CI 1.75-2.78, p < 0.001) and muscularis propria invasion (≥T2) (1.51, 1.13-2.03, p = 0.006), as well as worse TNM stage (2.26, 1.63-3.12, p < 0.001) and histological type (1.72, 1.34-2.20, p < 0.001), while no apparent relationship was found for serous membrane invasion (T4), venous invasion, and peritoneal metastasis. CONCLUSION: TFF3 may be a promising biomarker for GC, and the TFF3 expression is likely to be involved in the invasion, metastasis, and differentiation of GC.
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Biomarcadores de Tumor/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Factor Trefoil-3/genética , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Anciano , Área Bajo la Curva , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Sensibilidad y Especificidad , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Factor Trefoil-3/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/secundarioRESUMEN
Arsenic (As) toxicity can be a hazardous threat to sustainable agriculture and human health. Piriformospora indica (P. indica), as a beneficial endophytic fungus, is involved in the plant tolerance to stressful conditions. Here, the biochemical and molecular responses of rice plants to As (50 µM) phytotoxicity and P. indica inoculation as well as the role of P. indica in improving rice adaptation to As stress were evaluated. The results showed that As stress reduced chlorophylls content, chlorophyll fluorescence yield (Fv/Fm), electron transport rate (ETR) and growth. However, P. indica restored chlorophyll content and growth. P. indica decreased the contents of methylglyoxal and malondialdehyde by improving the activity of enzymes involved in the glyoxalase pathway and modulating the redox state of the ascorbic acid-glutathione cycle, and consequently, increased the plant tolerance to As toxicity. P. indica, by downregulating Lsi2 expression (involved in As translocation to the shoot) and upregulating PCS1 and PCS2 expression (involved in As sequestration in vacuoles), immobilized As in the roots and reduced damage to photosynthetic organs. P. indica increased iron (Fe) accumulation in the shoot under As toxicity by upregulating the expression of IRO2, YSL2 and FRDL1 genes. The results of the present study augmented our knowledge in using P. indica symbiosis in improving the tolerance of rice plants against As toxicity for sustainable agriculture.
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Adaptación Fisiológica/fisiología , Arsénico/toxicidad , Basidiomycota/fisiología , Oryza/fisiología , Contaminantes del Suelo/toxicidad , Arsénico/metabolismo , Basidiomycota/metabolismo , Clorofila/metabolismo , Humanos , Hierro/metabolismo , Malondialdehído/metabolismo , Oryza/metabolismo , Oryza/microbiología , Fotosíntesis , Raíces de Plantas/metabolismo , Raíces de Plantas/microbiología , Contaminantes del Suelo/metabolismo , SimbiosisRESUMEN
Salinity is one of the most important problems that adversely affect crops growth, productivity and quality worldwide. Salt Overly Sensitive 1 (SOS1) gene family plays vital roles in plant response to salt stress. Herein, we report the identification of the SOS family in wheat and the exploration of the expression profiles of SOSs under salt stress. Complete genome sequences of T. aestivum were downloaded from Ensembl plant database. Conservation and divergence of TaSOS1 family were conducted by using phylogenetic tree, gene structure and synteny distribution analysis. Expression profiles of TaSOS1s were obtained based on transcriptome and qRT-PCR analysis. Totally, 119 TaSOS1 proteins in wheat were identified at the genome-wide level and classified into three groups. Six motifs were conserved in TaSOS1 gene family. Moreover, 25 TaSOS1 genes had three copies distributing in three sub-genomes (A, B and D). A total of 32, 28 and 29 TaSOS1 genes were located on the sub-genomes A, B and D, respectively. Moreover, there were 19, 12, 6, 7, 28, 5 and 12 genes located on the three homologous of chromosomes 1, 2, 3, 4, 5, 6 and 7, respectively. Two genes were mapped to unattributed scaffolds. The duplication events analysis indicated that tandem repeats contributed to the expansion of the SOS1 family in wheat. Collinearity analysis demonstrated that segmental duplications play an important role in the expansion of SOS1 members. Chromosome 7, 5, 3, and 2 showed collinear relationship. Tissue specific expression pattern analysis revealed that 41 TaSOS1 genes expressed in various tissues, such as root, shoot, leaf, spike and grain. Transcriptomic analysis revealed that 28 and 26 genes were up- and down-regulated under salinity stress, respectively, of which 18 genes were further confirmed by RT-qPCR. The plants with high expression level of these genes displayed higher tolerance to salinity stress, stronger root system, higher Fv/Fm value and water potential. The results could be helpful for further elucidating the molecular mechanism of TaSOS1 related to salt tolerance in wheat and provide a toolkit for improving the salinity tolerance of wheat. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01009-y.
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Freezing stress is a serious environmental factor that obstructs plant development. The root endophytic fungus Piriformospora indica has proved to be effective to confer abiotic stress tolerance to host plants. To investigate how P. indica improves freezing tolerance, we compared the expression profiles of P. indica-colonized and uncolonized Arabidopsis seedlings either exposed to freezing stress or not. Nearly 24 million (93.5%) reads were aligned on the Arabidopsis genome. 634 genes were differentially expressed between colonized and uncolonized Arabidopsis exposed to freezing stress. Interestingly, 193 Arabidopsis genes did not respond to freezing stress but were up-regulated by P. indica under freezing stress. Freezing stress-responsive genes encoded various members of the WRKY, ERF, bHLH, HSF, MYB and NAC transcription factor families. The qRT-PCR analyses confirmed the high-throughput sequencing results for 28 genes. Functional enrichment analysis indicated that the fungus mainly controls genes for freezing-stress related proteins involved in lipid and ion transport, metabolism pathways and phytohormone signaling. Our findings identified novel target genes of P. indica in freezing-stress exposed plants and highlight the benefits of the endophyte for plants exposed to a less investigated environmental threat. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12298-020-00922-y) contains supplementary material, which is available to authorized users.
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The American Nurses Credentialing Center (ANCC) manages Magnet Recognition Program® certification. Candidates for this certification are required to pass a review comprising six compulsory documents and 84 sets of written documents in five model components as well as an onsite appraisal. The Magnet Recognition Program® for medical institutes is currently regarded as the highest honor in the nursing field. The series of measures necessary to establish a Magnet-recognized hospital is described in this article. Our hospital began preparation for recognition in January 2016, with the application submitted in May 2017. The required measures include establishing a Professional Practice Model, Governance Council, and National Database of Nursing Quality Indicators as well as implementing a mentoring plan. ANCC approved Magnet Recognition Program® recognition for our hospital in May 2020, making ours the first Magnet-recognized hospital in Taiwan. The nursing staff shared their experiences on their Magnet journey. Magnet-recognition demonstrates that a hospital is adequately equipped and trained to provide patients with outstanding nursing care and to operate an excellent nursing practice environment.
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Imanes , Personal de Enfermería en Hospital , Habilitación Profesional , Humanos , Taiwán , Estados UnidosRESUMEN
The in situ gelation of injectable precursors is desirable in the field of tissue regeneration, especially in the context of irregular defect filling. The current driving forces for fast gelation include the phase-transition of thermally sensitive copolymers, click chemical reactions with tissue components, and metal coordination effect. However, the rapid formation of tough hydrogels remains a challenge. Inspired by aerobic metabolism, we herein propose a tissue-fluid-triggered cascade enzymatic polymerization process catalyzed by glucose oxidase and ferrous glycinate for the ultrafast gelation of acryloylated chondroitin sulfates and acrylamides. The highly efficient production of carbon radicals and macromolecules contribute to rapid polymerization for soft tissue augmentation in bone defects. The copolymer hydrogel demonstrated the regeneration-promoting capacity of cartilage. As the first example of using artificial enzyme complexes for in situ polymerization, this work offers a biomimetic approach to the design of strength-adjustable hydrogels for bio-implanting and bio-printing applications.
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Cartílago/metabolismo , Glucosa Oxidasa/metabolismo , Hidrogeles/metabolismo , Líquido Sinovial/metabolismo , Agrecanos/genética , Agrecanos/metabolismo , Animales , Materiales Biomiméticos , Cartílago/química , Colágeno/genética , Colágeno/metabolismo , Glucosa Oxidasa/química , Hidrogeles/química , Masculino , Polimerizacion , Ratas , Ratas Sprague-Dawley , Líquido Sinovial/químicaRESUMEN
The mRNA precursor 3'-end modification factor NUDT21 is a major regulator of 3'UTR shortening and an important component of pre-mRNA cleavage and polyadenylation. However, its role in pathologic progress of small cell lung cancer (SCLC) remains unclear. In this study, we observed that NUDT21 expression is downregulated in SCLC tissues. Hypoxia-induced down-regulation of NUDT21 through HIF-1α. NUDT21 shRNA transduction promotes proliferation and inhibits apoptosis of A549 cells. NUDT21 inhibition also promotes tumor growth in a mouse xenograft model. Furthermore, we clarified that HIF-1α mediated NUDT21 downregulation which altered the expression patterns of two isoforms of GLS1, GAC and KGA. These results link the hypoxic tumor environments to aberrant glutamine metabolism which is important for cellular energy in SCLC cells. Therefore, NUDT21 could be considered as a potential target for the treatment of SCLC.
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Factor de Especificidad de Desdoblamiento y Poliadenilación/metabolismo , Glutaminasa/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Empalme del ARN/genética , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Células A549 , Proliferación Celular/genética , Células Cultivadas , Glutaminasa/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , MicroARNs/genética , Poliadenilación , Carcinoma Pulmonar de Células Pequeñas/metabolismoRESUMEN
BACKGROUND & PROBLEMS: Poor sleep quality during hospitalization may lead to post-hospital symptoms and increase readmission rates and mortality. Patients in our intensive care unit (ICU) reported low mean scores on the Richards-Campbell Sleep Questionnaire (RCSQ) during their third and fifth days of hospitalization (49.7 mm and 51.7 mm, respectively). Therefore, a project to improve sleep quality in the ICU was established. PURPOSE: To increase the mean RCSQ score from 51.7 mm to 76.0 mm on the fifth day. The fifth day timeframe was chosen because of the disease conditions of the patients and related clinical-medical factors. RESOLUTIONS: The project team proposed an evidence-based, sleep care bundle that included non-medication pain control, environmental regulation, improvement of the care process, and individualized sleep care. RESULTS: After implementing the bundled intervention, the mean RCSQ score of patients in our ICU increased from 49.7 mm to 55.9 mm on the third day and from 51.7 mm to 80.9 mm on the fifth day. CONCLUSIONS: This application of a sleep care bundle effectively improved the factors affecting sleep disturbance and improved quality of sleep in the patients in our intensive care unit.
Asunto(s)
Unidades de Cuidados Intensivos , Paquetes de Atención al Paciente/enfermería , Sueño , Humanos , Investigación en Evaluación de Enfermería , Trastornos del Sueño-Vigilia/prevención & control , Encuestas y CuestionariosRESUMEN
The design of enzyme mimics from stable and nonprotein systems is especially attractive for applications in highly specific cancer diagnosis and treatment, and it has become an emerging field in recent years. Herein, metal crosslinked polymeric nanogels (MPGs) were prepared using FeII ion coordinated biocompatible acryloyl-lysine polymer brushes obtained from an enzyme-catalyzed atomic transfer radical polymerization (ATRPase) method. The monoatomic and highly dispersed Fe ions in the MPGs serve as efficient crosslinkers of the gel network, and also as active centers of multienzyme mimics of superoxide dismutase (SOD) and peroxidase (POD). The catalytic activities were compared to those of conventional Fe-based nanozymes. Studies on both cells and animals verify that efficient reactive oxygen species (ROS) responsive biofluorescence imaging can be successfully realized using the MPGs.