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2.
Magn Reson Med ; 90(3): 1228-1241, 2023 09.
Article in English | MEDLINE | ID: mdl-37145035

ABSTRACT

PURPOSE: To design and implement a multi-coil (MC) array for B0 field generation for image encoding and simultaneous advanced shimming in a novel 1.5T head-only MRI scanner. METHODS: A 31-channel MC array was designed following the unique constraints of this scanner design: The vertically oriented magnet is very short, stopping shortly above the shoulders of a sitting subject, and includes a window for the subject to see through. Key characteristics of the MC hardware, the B0 field generation capabilities, and thermal behavior, were optimized in simulations prior to its construction. The unit was characterized via bench testing. B0 field generation capabilities were validated on a human 4T MR scanner by analysis of experimental B0 fields and by comparing images for several MRI sequences acquired with the MC array to those acquired with the system's linear gradients. RESULTS: The MC system was designed to produce a multitude of linear and nonlinear magnetic fields including linear gradients of up to 10 kHz/cm (23.5 mT/m) with MC currents of 5 A per channel. With water cooling it can be driven with a duty cycle of up to 74% and ramp times of 500 µs. MR imaging experiments encoded with the developed multi-coil hardware were largely artifact-free; residual imperfections were predictable, and correctable. CONCLUSION: The presented compact multi-coil array is capable of generating image encoding fields with amplitudes and quality comparable to clinical systems at very high duty cycles, while additionally enabling high-order B0 shimming capabilities and the potential for nonlinear encoding fields.


Subject(s)
Brain , Magnetic Resonance Imaging , Humans , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Phantoms, Imaging , Magnetic Fields , Artifacts
3.
Cancer Control ; 30: 10732748221148913, 2023.
Article in English | MEDLINE | ID: mdl-36599103

ABSTRACT

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), systemic inflammation response index (SIRI), and Onodera's prognostic nutritional index (OPNI) have been reported as prognostic markers for various cancers. We evaluated the prognostic value of the NLR, PLR, MLR, SII, SIRI, and OPNI for poorly-to moderately-differentiated cervical squamous cell carcinoma (CSCC). PATIENTS AND METHODS: We retrospectively analyzed the cases of 109 patients with early-stage poorly-to moderately-differentiated CSCC who underwent radical surgery at our institution in 2014-2017. The optimal cutoff points for the NLR, PLR, MLR, SII, SIRI, and OPNI were determined by receiver operating characteristic curves. Overall survival was analyzed by the Kaplan-Meier method. We performed a multivariate analysis using the Cox proportional hazard regression model to determine the independent prognostic indicators for early-stage poorly-to moderately-differentiated CSCC. RESULTS: The appropriate cutoff points were: NLR, 1.72; PLR, 111.96; MLR, .24; SII, 566.23; SIRI, 1.38; and OPNI, 52.68. The OS of the patients with a high OPNI (P = .04), low SII (P = .03), or low SIRI (P = .01) was significantly better. The uni- and multivariate analyses identified only the OPNI as an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC (P = .04 and P = .02). CONCLUSION: The OPNI is an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC; the NLR, PLR, MLR, SII, and SIRI are not.


Subject(s)
Carcinoma, Squamous Cell , Inflammation , Humans , Prognosis , Retrospective Studies , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Lymphocytes/pathology
4.
Cell Biochem Funct ; 41(5): 542-552, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37170668

ABSTRACT

PDZ-LIM domain-containing Protein 2 (PDLIM2) has been reported to be downregulated in ovarian cancer. However, its exact function and mechanism in regulating ovarian cancer progression have not been elucidated. This work researched the exert effect and mechanism of PDLIM2 on ovarian cancer progression. Briefly, PDLIM2 expression in clinical tissues of ovarian cancer patients and cells was investigated by qRT-PCR and Western blot. The function of PDLIM2 on the proliferation, colony formation, migration and invasion of ovarian cancer cells was explored via cell counting kit-8, colony formation and Transwell assays. To verify whether PDLIM2 regulates ovarian cancer progression via regulating the transforming growth factor-ß (TGF-ß)/Smad pathway, exogenous TGF-ß (10 ng/mL) treatment was performed on the PDLIM2-overexpressed ovarian cancer cells. PDLIM2 effect on the in vivo growth of ovarian cancer cells was researched by establishing a xenograft tumor model. Immunohistochemistry and Western blot were performed to protein expression in cells and tissues. As a result, PDLIM2 was low-expressed in ovarian cancer tissues/cells. PDLIM2 upregulation attenuated the proliferation, colony formation, migration, invasion and epithelial-mesenchymal transition (EMT) of ovarian cancer cells, and inactivated the TGF-ß/Smad pathway. The opposite results were found in the PDLIM2-silenced ovarian cancer cells. Exogenous TGF-ß treatment abrogated the inhibition of PDLIM2 on the malignant behavior of ovarian cancer cells. PDLIM2 upregulation attenuated the in vivo growth and EMT of ovarian cancer cells. Thus, PDLIM2 attenuates the proliferation, migration, invasion and EMT of ovarian cancer cells via inactivating the TGF-ß/Smad pathway. PDLIM2 may be a usefully target for ovarian cancer treatment.


Subject(s)
Ovarian Neoplasms , Transforming Growth Factor beta , Humans , Female , Transforming Growth Factor beta/metabolism , Cell Movement , Smad Proteins/metabolism , Cell Line, Tumor , Signal Transduction , Epithelial-Mesenchymal Transition , Transforming Growth Factor beta1/metabolism , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , Microfilament Proteins/pharmacology , LIM Domain Proteins/genetics , LIM Domain Proteins/metabolism , LIM Domain Proteins/pharmacology
5.
J Integr Plant Biol ; 65(5): 1226-1240, 2023 May.
Article in English | MEDLINE | ID: mdl-36511120

ABSTRACT

RAV1 (Related to ABI3/VP1) is a plant-specific B3 and AP2 domain-containing transcription factor that acts as a negative regulator of growth in many plant species. The expression of RAV1 is downregulated by brassinosteroids (BRs); large-scale transcriptome analyses have shown that the expression of RAV1 was previously targeted by BRI1-EMS-SUPPRESOR1 (BES1) and BRASSINAZOLE-RESISTANT1 (BZR1), which are critical transcription factors for the BR-signaling process. Using RAV1-overexpressing transgenic plants, we showed that RAV1 overexpression reduced the BR signaling capacity, resulting in the downregulation of BR biosynthetic genes and BES1 expression. Furthermore, we demonstrated that BES1, not BZR1, is directly bound to the RAV1 promoter and repressed RAV1 expression, and vice versa; RAV1 is also bound to the BES1 promoter and repressed BES1 expression. This mutual inhibition was specific to RAV1 and BES1 because RAV1 exhibited binding activity to the BZR1 promoter but did not repress BZR1 expression. We observed that constitutively activated BR signaling phenotypes in bes1-D were attenuated by the repression of endogenous BES1 expression in transgenic bes1-D plants overexpressing RAV1. RNA-sequencing analysis of RAV1-overexpressing transgenic plants and bes1-D mutant plants revealed differentially expressed genes by RAV1 and BES1 and genes that were oppositely co-regulated by RAV1 and BES1. RAV1 and BES1 regulated different transcriptomes but co-regulated a specific set of genes responsible for the balance between growth and defense. These results suggested that the mutual inhibitory transcriptional activities of RAV1 and BES1 provide fine regulatory mechanisms for plant growth and development.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/growth & development , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Brassinosteroids/pharmacology , Brassinosteroids/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Plant/genetics , Plant Development , Plants, Genetically Modified/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
6.
NMR Biomed ; 35(8): e4739, 2022 08.
Article in English | MEDLINE | ID: mdl-35393706

ABSTRACT

B0 inhomogeneity leads to imaging artifacts in cardiac magnetic resonance imaging (MRI), in particular dark band artifacts with steady-state free precession pulse sequences. The limited spatial resolution of MR-derived in vivo B0 maps and the lack of population data prevent systematic analysis of the problem at hand and the development of optimized B0 shim strategies. We used readily available clinical computed tomography (CT) images to simulate the B0 conditions in the human heart at high spatial resolution. Calculated B0 fields showed consistency with MRI-based B0 measurements. The B0 maps for both the simulations and in vivo measurements showed local field inhomogeneities in the vicinity of lung tips with dominant Z3 spherical harmonic terms in the field distribution. The presented simulation approach allows for the derivation of B0 field conditions at high spatial resolution from CT images and enables the development of subject- and population-specific B0 shim strategies for the human heart.


Subject(s)
Brain , Magnetic Resonance Imaging , Artifacts , Heart/diagnostic imaging , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed
7.
Nature ; 531(7596): 637-641, 2016 Mar 31.
Article in English | MEDLINE | ID: mdl-26886793

ABSTRACT

Animals are grouped into ~35 'phyla' based upon the notion of distinct body plans. Morphological and molecular analyses have revealed that a stage in the middle of development--known as the phylotypic period--is conserved among species within some phyla. Although these analyses provide evidence for their existence, phyla have also been criticized as lacking an objective definition, and consequently based on arbitrary groupings of animals. Here we compare the developmental transcriptomes of ten species, each annotated to a different phylum, with a wide range of life histories and embryonic forms. We find that in all ten species, development comprises the coupling of early and late phases of conserved gene expression. These phases are linked by a divergent 'mid-developmental transition' that uses species-specific suites of signalling pathways and transcription factors. This mid-developmental transition overlaps with the phylotypic period that has been defined previously for three of the ten phyla, suggesting that transcriptional circuits and signalling mechanisms active during this transition are crucial for defining the phyletic body plan and that the mid-developmental transition may be used to define phylotypic periods in other phyla. Placing these observations alongside the reported conservation of mid-development within phyla, we propose that a phylum may be defined as a collection of species whose gene expression at the mid-developmental transition is both highly conserved among them, yet divergent relative to other species.


Subject(s)
Body Patterning , Embryonic Development , Phylogeny , Animals , Body Patterning/genetics , Conserved Sequence/genetics , Embryonic Development/genetics , Evolution, Molecular , Gene Expression Regulation, Developmental , Gene Regulatory Networks , Genes, Developmental/genetics , Models, Biological , Phenotype , Species Specificity , Transcriptome/genetics
8.
Int J Mol Sci ; 23(15)2022 Jul 31.
Article in English | MEDLINE | ID: mdl-35955636

ABSTRACT

Highly efficient gene delivery systems are essential for genetic engineering in plants. Traditional delivery methods have been widely used, such as Agrobacterium-mediated transformation, polyethylene glycol (PEG)-mediated delivery, biolistic particle bombardment, and viral transfection. However, genotype dependence and other drawbacks of these techniques limit the application of genetic engineering, particularly genome editing in many crop plants. There is a great need to develop newer gene delivery vectors or methods. Recently, nanomaterials such as mesoporous silica particles (MSNs), AuNPs, carbon nanotubes (CNTs), and layer double hydroxides (LDHs), have emerged as promising vectors for the delivery of genome engineering tools (DNA, RNA, proteins, and RNPs) to plants in a species-independent manner with high efficiency. Some exciting results have been reported, such as the successful delivery of cargo genes into plants and the generation of genome stable transgenic cotton and maize plants, which have provided some new routines for genome engineering in plants. Thus, in this review, we summarized recent progress in the utilization of nanomaterials for plant genetic transformation and discussed the advantages and limitations of different methods. Furthermore, we emphasized the advantages and potential broad applications of nanomaterials in plant genome editing, which provides guidance for future applications of nanomaterials in plant genetic engineering and crop breeding.


Subject(s)
Metal Nanoparticles , Nanotubes, Carbon , CRISPR-Cas Systems , Gene Editing/methods , Gene Transfer Techniques , Genetic Engineering/methods , Genome, Plant , Gold , Plant Breeding/methods , Plants/genetics , Plants, Genetically Modified/genetics
9.
Biochem Biophys Res Commun ; 573: 125-131, 2021 10 08.
Article in English | MEDLINE | ID: mdl-34403809

ABSTRACT

Being sessile, plants must deploy highly exquisite systems to respond to various internal and external signals for modulating growth and development throughout their lifespan. Many studies on Arabidopsis have shown that leucine-rich repeat-containing receptor-like kinases, including BRI1-associated receptor kinase 1 (BAK1) and receptor-like protein kinase 1 (RPK1), are suitable for such pleiotropic demands of plants. Previously, BAK1 and RPK1 were independently proven to be involved in the regulation of premature cell death. BAK1 inhibits spontaneous cell death and promotes defense-induced cell death. Meanwhile, RPK1 mediates reactive oxygen species (ROS) production through complexation with CaM4 and RbohF in an age-dependent manner. In the present study, RPK1-induced cell death and growth retardation were abolished both with respect to the phenotype and ROS production in bak1 mutants. Moreover, BAK1 interacts with RPK1 and mediates its unidirectional phosphorylation in plants. Further, BAK1-mediated RPK1 phosphorylation is indispensable for RPK1-CaM4 interaction, which is vital for ROS production, resulting in cell death. The presence of BAK1 enhanced the expression of cell death- and senescence-related genes, such as ORE1, PR1, SAG12, and SIRK in RPK1-mediated signaling cascades. Overall, in Arabidopsis, in addition to independent cell death regulation by BAK1 and RPK1, multiple-layers control cell death and premature senescence via the coordinated action of BAK1 and RPK1.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Protein Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , Cell Death , Phosphorylation
10.
J Exp Bot ; 72(15): 5494-5507, 2021 07 28.
Article in English | MEDLINE | ID: mdl-34021330

ABSTRACT

Open Stomata 1 (OST1)/SnRK2.6 is a critical component connecting abscisic acid (ABA) receptor complexes and downstream components, including anion channels and transcription factors. Because OST1 is a serine/threonine kinase, several autophosphorylation sites have been identified, and S175 is known to be critical for its kinase activity. We previously reported that BAK1 interacts with and phosphorylates OST1 to regulate ABA signaling. Here, we mapped additional phosphosites of OST1 generated by autophosphorylation and BAK1-mediated transphosphorylation in Arabidopsis. Many phosphosites serve as both auto- and transphosphorylation sites, especially those clustered in the activation loop region. Phospho-mimetic transgenic plants containing quadruple changes in Y163, S164, S166, and S167 rescued ost1 mutant phenotypes, activating ABA signaling outputs. Moreover, we found that OST1 is an active tyrosine kinase, autophosphorylating the Y182 site. ABA induced tyrosine phosphorylation of Y182 in OST1; this event is catalytically important for OST1 activity in plants. ABA-Insensitive 1 (ABI1) and its homologs ABI2 and HAB1, PP2C serine/threonine phosphatases that are known to dephosphorylate OST1 at S175, function as tyrosine phosphatases acting on the phosphorylated Y182 site. Our results indicate that phosphorylation cycles between OST1 and ABI1, which have dual specificity for tyrosine and serine/threonine, coordinately control ABA signaling in Arabidopsis.


Subject(s)
Abscisic Acid , Arabidopsis Proteins , Protein Kinases , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Phosphorylation , Protein Kinases/genetics , Protein Kinases/metabolism , Protein-Tyrosine Kinases , Serine , Threonine
11.
BMC Womens Health ; 21(1): 134, 2021 03 31.
Article in English | MEDLINE | ID: mdl-33789656

ABSTRACT

BACKGROUND: This study aimed to investigate the clinical and pathological characteristics, and the recurrence and prognostic factors of borderline ovarian tumors (BOTs). METHODS: The data of 286 patients admitted to hospital and followed up for more than ten months were analyzed retrospectively to study the clinicopathological characteristics and related factors of recurrence. RESULTS: The median age of the patients was 42.06 ± 14.97 years, and the duration of the follow-up ranged from 10-109 months. During the follow-up period, 40 patients had a recurrence. Of these patients, 36 were ≤ 40 years, and patients with premenopausal recurrence accounted for 20.5% (36/176). In patients undergoing conservative treatment or radical operations, the recurrence rates were 21.3% and 1.8%, respectively, and they were 13.4% (36/268) in patients at Federation International of Gynecology and Obstetrics (FIGO) stage I, and 22.2% (4/18) in patients at an advanced stage. Postoperative pathology revealed that 40 patients had micropapillary tumors, among whom ten patients (25%) had a recurrence, and 19 patients had complications with interstitial infiltration. Of these 19 patients, six had a recurrence (31.5%). Another 22 patients had complications with calcified sand bodies; among these, eight patients (36.4%) had a recurrence. All the differences were statistically significant (P < 0.05). There were four cancer-related deaths during the follow-up period. Late FIGO stage, conservative operation, and a high level of carbohydrate antigen 125 (CA125) were independent risk factors for the recurrence of BOTs. CONCLUSION: BOTs usually occur in women under 40 years, have an occult onset, and half of the patients have no obvious clinical manifestations. Serum CA125 level can be used as a tumor marker to detect BOTs and the risk of its recurrence. Operation mode and FIGO stage are important independent factors for the recurrence of BOTs.


Subject(s)
Ovarian Neoplasms , Biomarkers, Tumor , CA-125 Antigen , Child , Child, Preschool , Female , Humans , Infant , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/pathology , Pregnancy , Prognosis , Retrospective Studies
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(6): 645-649, 2021 Jun.
Article in Zh | MEDLINE | ID: mdl-34130789

ABSTRACT

Peak expiratory flow (PEF) is a portable, reliable, and inexpensive method for lung function assessment. PEF can reflect expiratory airflow limitation and its variability can document reversibility, which provides an objective basis for the diagnosis of asthma in children. Short-term PEF monitoring can be an important aid in the management of acute asthma exacerbations, identification of possible triggers, and assessment of response to treatment. Long-term PEF monitoring can assist in the assessment of asthma control and warning of acute exacerbations, and this is useful for children with severe asthma. This article reviews the measurements, influencing factors, interpretation, and application of PEF, and its role in the diagnosis and management of asthma in children, to provide references for the clinical application of PEF in children.


Subject(s)
Asthma , Asthma/diagnosis , Asthma/therapy , Child , Humans , Peak Expiratory Flow Rate , Respiratory Function Tests
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(3): 265-270, 2021 Mar.
Article in Zh | MEDLINE | ID: mdl-33691920

ABSTRACT

OBJECTIVE: To study the correlation between the bronchial dilation test (BDT) and asthma control level in children with asthma. METHODS: A total of 153 children with asthma, aged 5-14 years, who attended the outpatient service from March 2016 to March 2018 were enrolled. According to the presence or absence of atopic constitution, they were divided into an allergic group with 79 children and a non-allergic group with 74 children. The correlation between BDT and Childhood Asthma Control Test (C-ACT) scores was analyzed for both groups. RESULTS: All basic pulmonary function parameters were positively correlated with C-ACT scores in the non-allergic group (P < 0.05). Except the forced vital capacity, peak expiratory flow and maximal expiratory flow at 25% vital capacity in percent predicted values, the other pulmonary function parameters were positively correlated with C-ACT scores in the allergic group (P < 0.05). The improvement rates of all BDT parameters (except maximal expiratory flow at 25% vital capacity in the allergic group and maximal expiratory flow at 50% vital capacity in the non-allergic group) were negatively correlated with C-ACT scores in the two groups (P < 0.05). CONCLUSIONS: The improvement rate of BDT is well correlated with C-ACT scores in children with asthma, suggesting that BDT can be used as an index for predicting asthma control level.


Subject(s)
Asthma , Adolescent , Child , Child, Preschool , Dilatation , Forced Expiratory Volume , Humans , Lung , Vital Capacity
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(11): 1119-1126, 2021 Nov 15.
Article in English, Zh | MEDLINE | ID: mdl-34753543

ABSTRACT

OBJECTIVES: To establish a predictive equation for commonly used pulmonary ventilation function parameters in children aged 6-<16 years in northeast China. METHODS: A total of 504 healthy children from Liaoning, Jilin, and Heilongjiang provinces of China were selected for the prospective study, among whom there were 242 boys and 262 girls. The JAEGER MasterScreen Pneumo spirometer was used to measure pulmonary ventilation function. With the measured values of 10 parameters, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, and back-extrapolated volume (BEV), as dependent variables and age, body height, and body weight as independent variables, the stepwise multivariate regression method was used to establish the regression equation for children of different sexes. The mean of relative prediction error was used to evaluate the applicability of the predictive equation. RESULTS: The boys aged 9-<10 years and 15-<16 years had significantly higher body height, FVC, and FEV1 than the girls of the same age (P<0.05), and the boys aged 9-<10, 10-<11, 11-<12, and 13-<14 years had a significantly lower FEV1/FVC ratio than the girls of the same age (P<0.05). The correlation analysis showed that all parameters, except FEV1/FVC ratio and BEV/FVC ratio, were significantly positively correlated with age, body height, and body weight (P<0.001). Further regression analysis showed that age and body height were the influencing factors for most parameters, while body weight was less frequently included in the regression equation. Compared with the predictive equations from previous studies, the regression equation established in this study had relatively good applicability in the study population. CONCLUSIONS: A new predictive equation for the main pulmonary ventilation function parameters has been established in this study for children aged 6-<16 years in northeast China, which provides a basis for accurate judgment of pulmonary function abnormalities in clinical practice.


Subject(s)
Pulmonary Ventilation , Schools , Child , China , Female , Forced Expiratory Volume , Humans , Male , Prospective Studies , Reference Values , Vital Capacity
15.
J Exp Bot ; 71(4): 1491-1502, 2020 02 19.
Article in English | MEDLINE | ID: mdl-31665747

ABSTRACT

Regulation of plant water status occurs via abscisic acid (ABA)-induced stomatal closure. Open Stomata 1 (OST1) is a critical ABA signaling component regulating this process in guard cells. We previously reported that BRI1-associated receptor kinase 1 (BAK1) positively regulates ABA-induced stomatal closure by interacting with and phosphorylating OST1. Here, using Arabidopsis, we show that the receptor-like protein kinase 1 (RPK1), previously known to be induced by ABA, is a positive ABA-signaling component in guard cell movement, and interacts with OST1. ABA-inducible expression patterns were observed in RPK1 and OST1, but not in BAK1. We investigated the underlying mechanisms by which the RPK1-OST1 and BAK1-OST1 complexes interact in stomatal guard cells by monitoring the complex formation continuously using fluorescence resonance energy transfer analyses. We found that the BAK1-OST1 complex was formed earlier than the RPK1-OST1 complex in response to ABA. In vitro and semi-in vivo kinase assays revealed that a transphosphorylation event occurred in the RPK1-OST1 complex, which differs from that in the BAK1-OST1 complex, wherein only OST1 phosphorylation occurred via BAK1. ABA-insensitive 1 (ABI1) only dephosphorylated OST1 in the BAK1-OST1 complex, but dephosphorylated both RPK1 and OST1 proteins in the RPK1-OST1 complex. Our results suggest that there are multiple coordinated ABA signaling systems to regulate stomatal movement.


Subject(s)
Abscisic Acid , Arabidopsis Proteins , Plant Stomata , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Plant Stomata/metabolism , Protein Kinases/genetics , Protein Kinases/metabolism , Protein Serine-Threonine Kinases , Reactive Oxygen Species , Signal Transduction
16.
Exp Cell Res ; 364(2): 168-174, 2018 03 15.
Article in English | MEDLINE | ID: mdl-29408536

ABSTRACT

Asthma is a heterogeneous clinical syndrome characterized by airway inflammation, hyper-responsiveness and remodeling. Airway remodeling is irreversible by current antiasthmatic drugs, and it is the main cause of severe asthma. Airway smooth muscle cells (ASMCs) act as the main effector cells for airway remodeling; the proliferation and hypertrophy of which are involved in airway remodeling. Caveolin (Cav)- 1 is present on the surface of ASMCs, which is involved in cell cycle and signal transduction regulation, allowing ASMCs to change from proliferation to apoptosis. The extracellular signal-regulated kinase (ERK)1/2 signaling pathway is a common pathway regulated by various proliferative factors, which demonstrates a regulatory role in airway remodeling of asthma. There have been many studies on the correlation between vasoactive intestinal peptide (VIP) and airway reactivity and inflammation in asthma, but the functions and related mechanisms of ASMCs remain unclear. In this study, we established an airway remodeling model in asthmatic mice, and concluded that VIP inhibits airway remodeling in vivo. The in vitro effect of VIP on interleukin-13-induced proliferation of ASMCs was studied by examining the effects of VIP on expression of ERK1/2, phospho-ERK1/2 and Cav-1 in ASMCs, as well as changes in cell cycle distribution. VIP inhibited phosphorylation of the ERK1/2 signaling pathway and expression of Cav-1 on ASMCs and decreased the proportion of S phase cells in the cell cycle, thus inhibiting the proliferation of ASMCs. This study provides a novel therapeutic mechanism for the treatment of asthma.


Subject(s)
Asthma/drug therapy , Disease Models, Animal , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Myocytes, Smooth Muscle/drug effects , Vasoactive Intestinal Peptide/pharmacology , Airway Remodeling/drug effects , Animals , Asthma/metabolism , Asthma/pathology , Cell Proliferation/drug effects , Cells, Cultured , Female , MAP Kinase Signaling System/drug effects , Mice , Mice, Inbred BALB C , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/metabolism
17.
Biochem Biophys Res Commun ; 504(1): 143-148, 2018 09 26.
Article in English | MEDLINE | ID: mdl-30170727

ABSTRACT

Proper regulation of stomatal movement in response to various environmental stresses or developmental status is critical for the adaptation of many plant species to land. In plants, abscisic acid (ABA)-induced stomatal closure is a well-adapted method of regulating water status. In addition to ABA, we previously showed that plant-specific steroidal hormone, brassinosteroid (BR), also induces stomatal closure; however, BR modulates ABA-induced stomatal closure negatively at high concentrations. In this study, we further investigated the cross-talk between ABA and BR in relation to stomatal movement. In contrast to previous reports that ABA-induced stomatal closure was inhibited by brassinolide (BL), the most active BR, we showed that BL-induced stomatal closure was enhanced by ABA, indicating that the sequence of ABA or BL treatments led to different results. We found that this phenomenon occurred because the guard cells still had the capacity to be closed further by ABA, as the degree of stomatal closure by BL was always less than that by ABA. We also found that BL-induced stomatal closure required Open Stomata 1 (OST1) activity and the induced expression of OST1 was indifferent to the sequence of ABA and/or BL treatments. In addition, we examined the underlying mechanism by which inhibition of ABA-induced stomatal closure by BL occurred. We revealed that the downregulation of ABA-biosynthetic genes by BL resulted in a lower accumulation of ABA. These results suggested that the regulation of stomatal movement is finely controlled by the combined effects of plant hormones, ABA and BR.


Subject(s)
Abscisic Acid/pharmacology , Arabidopsis Proteins/metabolism , Arabidopsis/physiology , Brassinosteroids/pharmacology , Plant Stomata/drug effects , Protein Kinases/metabolism , Arabidopsis Proteins/genetics , Gene Expression Regulation, Plant/drug effects , Mutation , Plant Growth Regulators/metabolism , Plant Leaves/physiology , Protein Kinases/genetics , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Steroids, Heterocyclic/pharmacology , Time Factors
18.
Nature ; 482(7384): 251-5, 2012 Feb 08.
Article in English | MEDLINE | ID: mdl-22318606

ABSTRACT

First identified as histone-modifying proteins, lysine acetyltransferases (KATs) and deacetylases (KDACs) antagonize each other through modification of the side chains of lysine residues in histone proteins. Acetylation of many non-histone proteins involved in chromatin, metabolism or cytoskeleton regulation were further identified in eukaryotic organisms, but the corresponding enzymes and substrate-specific functions of the modifications are unclear. Moreover, mechanisms underlying functional specificity of individual KDACs remain enigmatic, and the substrate spectra of each KDAC lack comprehensive definition. Here we dissect the functional specificity of 12 critical human KDACs using a genome-wide synthetic lethality screen in cultured human cells. The genetic interaction profiles revealed enzyme-substrate relationships between individual KDACs and many important substrates governing a wide array of biological processes including metabolism, development and cell cycle progression. We further confirmed that acetylation and deacetylation of the catalytic subunit of the adenosine monophosphate-activated protein kinase (AMPK), a critical cellular energy-sensing protein kinase complex, is controlled by the opposing catalytic activities of HDAC1 and p300. Deacetylation of AMPK enhances physical interaction with the upstream kinase LKB1, leading to AMPK phosphorylation and activation, and resulting in lipid breakdown in human liver cells. These findings provide new insights into previously underappreciated metabolic regulatory roles of HDAC1 in coordinating nutrient availability and cellular responses upstream of AMPK, and demonstrate the importance of high-throughput genetic interaction profiling to elucidate functional specificity and critical substrates of individual human KDACs potentially valuable for therapeutic applications.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Histone Deacetylase 1/metabolism , Lysine/metabolism , p300-CBP Transcription Factors/metabolism , AMP-Activated Protein Kinase Kinases , AMP-Activated Protein Kinases/chemistry , AMP-Activated Protein Kinases/genetics , Acetylation , Biocatalysis , Catalytic Domain , Cell Cycle , Cell Line , Cell Line, Tumor , Histone Deacetylase 1/genetics , Humans , Phosphorylation , Protein Binding , Protein Serine-Threonine Kinases/metabolism , RNA Interference , Substrate Specificity , p300-CBP Transcription Factors/genetics
19.
Nucleic Acids Res ; 44(D1): D764-73, 2016 Jan 04.
Article in English | MEDLINE | ID: mdl-26578570

ABSTRACT

Planarian flatworms are in the midst of a renaissance as a model system for regeneration and stem cells. Besides two well-studied model species, hundreds of species exist worldwide that present a fascinating diversity of regenerative abilities, tissue turnover rates, reproductive strategies and other life history traits. PlanMine (http://planmine.mpi-cbg.de/) aims to accomplish two primary missions: First, to provide an easily accessible platform for sharing, comparing and value-added mining of planarian sequence data. Second, to catalyze the comparative analysis of the phenotypic diversity amongst planarian species. Currently, PlanMine houses transcriptomes independently assembled by our lab and community contributors. Detailed assembly/annotation statistics, a custom-developed BLAST viewer and easy export options enable comparisons at the contig and assembly level. Consistent annotation of all transcriptomes by an automated pipeline, the integration of published gene expression information and inter-relational query tools provide opportunities for mining planarian gene sequences and functions. For inter-species comparisons, we include transcriptomes of, so far, six planarian species, along with images, expert-curated information on their biology and pre-calculated cross-species sequence homologies. PlanMine is based on the popular InterMine system in order to make the rich biology of planarians accessible to the general life sciences research community.


Subject(s)
Databases, Genetic , Planarians/genetics , Animals , Data Mining , Gene Expression Profiling , Genes, Helminth , Phenotype , Planarians/metabolism , Sequence Analysis
20.
Biochem Biophys Res Commun ; 484(4): 781-786, 2017 03 18.
Article in English | MEDLINE | ID: mdl-28153720

ABSTRACT

Since the BRI1-Associated Receptor Kinase 1 (BAK1) was firstly identified as a co-receptor of BRI1 that mediates brassinosteroids (BR) signaling, the functional roles of BAK1, as a versatile co-receptor for various ligand-binding leucine-rich repeat (LRR)-containing receptor-like kinase (RLKs), are being extended to involvement with plant immunity, cell death, stomatal development and ABA signaling in plants. During more than a decade of research on the BAK1, it has been known that transgenic Arabidopsis plants overexpressing BAK1 tagged with various reporters do not fully represent its natural functions. Therefore, in this study, we characterized the transgenic plants in which native BAK1 is overexpressed driven by its own promoter. We found that those transgenic plants were more sensitive to BR signaling but showed reduced growth patterns accompanied with spontaneous cell death features that are different from those seen in BR-related mutants. We demonstrated that more salicylic acid (SA) and hydrogen peroxide were accumulated and that expressions of the genes that are known to regulate cell death, such as BONs, BIRs, and SOBIR, were increased in the BAK1-overexpressing transgenic plants. These results suggest that pleiotropic phenotypic alterations shown in the BAK1- overexpressing transgenic plants result from the constitutive activation of SA-mediated defense responses.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Apoptosis/physiology , Arabidopsis Proteins/metabolism , Arabidopsis/physiology , Gene Expression Regulation, Plant/physiology , Protein Serine-Threonine Kinases/metabolism , Salicylic Acid/metabolism , Feedback, Physiological/physiology , Plants, Genetically Modified/physiology , Up-Regulation/physiology
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