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1.
Front Oncol ; 14: 1357612, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628664

RESUMO

Paragangliomas (PGLs) are rare neuroendocrine tumors which overproduce catecholamines (CAs). They are extra-adrenal, catecholamine-secreting tumors occurring outside the adrenal glands. Gastric PGLs originating from extra-adrenal paraganglia are exceptionally rare, and their presentation in geriatric patients further adds to the complexity of diagnosis and management. A 72-year-old male patient presented with enduring left upper abdominal pain and anemia persisting for over a year, and hypertension for six months. Physical examination revealed epigastric discomfort and pallor. Computed tomography scans revealed enlarged lymph nodes in the lesser curvature of the stomach and thickening of the gastric antrum wall with concavity. The patient underwent three cycles of neoadjuvant therapy before radical gastrectomy for gastric cancer. These imaging findings were confirmed during surgery and intraoperative blood pressure was in fluctuation. After the successful resection of the tumor, postoperative pathology confirmed paraganglioma. During postoperative examination, it was observed that the patient's CAs and their metabolites had returned to within the normal range. Combined with the existing ten literatures, we retrospective report the clinical and pathological characteristics and treatment strategies of the rare gastric paraganglioma.

2.
J Integr Plant Biol ; 66(1): 12-16, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38103031

RESUMO

The plasma membrane-localized phytosulfokine receptor-like protein TaRLK-6A, interacting with TaSERK1, positively regulates the expression of defense-related genes in wheat, consequently promotes host resistance to Fusarium crown rot.


Assuntos
Fusarium , Triticum , Triticum/genética , Fusarium/fisiologia , Doenças das Plantas/genética
3.
Medicine (Baltimore) ; 102(51): e36734, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38134072

RESUMO

RATIONALE: Paraesophageal hernias, accounting for a mere 5% to 10% of all hiatal hernias, occasionally present an exceedingly uncommon yet gravely consequential complication characterized by the inversion of the stomach. Delving into the clinical manifestations and optimal therapeutic approaches for patients afflicted by this condition merits substantial exploration. PATIENT CONCERNS: A 60-year-old man was referred to our hospital with acute onset of severe epigastric pain, abdominal distension, and vomiting. A chest radiograph unveiled an elevated left diaphragmatic dome accompanied by a pronounced rightward shift of the mediastinum. Subsequent abdominal computed tomography imaging delineated the migration of the stomach, spleen, and colon into the left hemithorax, facilitated by a significant diaphragmatic defect. DIAGNOSES: The diagnosis of a giant paraesophageal hernia with complete gastric inversion was established through a comprehensive evaluation of the patient's clinical manifestations and imaging findings. INTERVENTIONS: Surgical intervention was performed on the patient. During the procedure, a left diaphragmatic defect measuring approximately 10 × 8 cm was identified and meticulously repositioned, followed by the repair of the diaphragmatic hernia. The herniated contents comprised the pancreas, stomach, spleen, a segment of the colon, and a portion of the greater omentum. OUTCOMES: The patient experienced a smooth postoperative recuperation and was discharged 12 days following the surgical procedure. Subsequently, during a 7-month follow-up period, the patient continued to exhibit favorable progress and recovery. LESSONS: Paraesophageal hernias are rare, and the presence of an inverted stomach in a giant paraesophageal hernia is exceptionally uncommon. Clinical presentation lacks distinct features and can lead to misdiagnosis. This case emphasizes the importance of timely surgical intervention guided by imaging, offering valuable clinical insights.


Assuntos
Hérnia Hiatal , Hérnias Diafragmáticas Congênitas , Masculino , Humanos , Pessoa de Meia-Idade , Hérnia Hiatal/complicações , Hérnia Hiatal/cirurgia , Estômago/cirurgia , Hérnias Diafragmáticas Congênitas/complicações , Diafragma , Dor Abdominal
4.
Int J Mol Sci ; 24(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37047146

RESUMO

Fusarium pseudograminearum is a major pathogen for the destructive disease Fusarium crown rot (FCR) of wheat (Triticum aestivum). The cytosolic Acetoacetyl-CoA thiolase II (AACT) is the first catalytic enzyme in the mevalonate pathway that biosynthesizes isoprenoids in plants. However, there has been no investigation of wheat cytosolic AACT genes in defense against pathogens including Fusarium pseudograminearum. Herein, we identified a cytosolic AACT-encoding gene from wheat, named TaAACT1, and demonstrated its positively regulatory role in the wheat defense response to F. pseudograminearum. One haplotype of TaAACT1 in analyzed wheat genotypes was associated with wheat resistance to FCR. The TaAACT1 transcript level was elevated after F. pseudograminearum infection, and was higher in FCR-resistant wheat genotypes than in susceptible wheat genotypes. Functional analysis indicated that knock down of TaAACT1 impaired resistance against F. pseudograminearum and reduced the expression of downstream defense genes in wheat. TaAACT1 protein was verified to localize in the cytosol of wheat cells. TaAACT1 and its modulated defense genes were rapidly responsive to exogenous jasmonate treatment. Collectively, TaAACT1 contributes to resistance to F. pseudograminearum through upregulating the expression of defense genes in wheat. This study sheds new light on the molecular mechanisms underlying wheat defense against FCR.


Assuntos
Fusarium , Fusarium/genética , Triticum/genética , Doenças das Plantas/genética , Genótipo
5.
Curr Pharm Des ; 29(9): 686-696, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36967466

RESUMO

AIMS: This study aims to develop a novel tumor-targeted molecular probe for pancreatic cancer imaging. The objective of this is to prepare a CKAAKN peptide-conjugated poly (lactic-co-glycolic acid)-poly (ethylene glycol) amphiphilic polymer (CKAAKN-PEG-PLGA) for the tumor-targeted delivery of magnetic resonance imaging (MRI) contrast agent ultrasmall superparamagnetic iron oxide (USPIO). BACKGROUND: The early diagnosis of pancreatic cancer is crucial for improving its prognosis, but the clinical application of many diagnostic methods is limited owing to a lack of specificity and sensitivity. METHODS: CKAAKN-PEG-PLGA was synthesized by the amidation reaction. USPIO-loaded polymeric magnetic nanoparticles (USPIO@CKAAKN-PEG-PLGA) were prepared by the emulsion solvent evaporation method. The in vitro tumor targeting and bio-safety of nanoparticles were evaluated by targeted cellular uptake, MR imaging and MTT assay. RESULTS: USPIO@CKAAKN-PEG-PLGA nanoparticles showed excellent biosafety with an average diameter of 104.5 ± 4.1 nm. Modification of CKAAKN peptide could improve USPIO binding ability to internalize into CKAAKN-positive BxPC-3 cells compared with non-targeting nanoparticles and the control group. The relative fluorescence intensity in BxPC-3 and HPDE6-C7 cells was 23.77 ± 4.18 and 6.44 ± 2.10 (p < 0.01), and respectively became 16.13 ± 0.83 and 11.74 ± 1.74 after the addition of free CKAAKN peptide. In vitro MR imaging studies showed that an obvious decrease in the signal intensity was observed in the targeted nanoparticles group incubated with BxPC-3 and HPDE6-C7 cells (p < 0.05). CONCLUSION: USPIO@CKAAKN-PEG-PLGA nanoparticles could significantly enhance the tumor specificity of USPIO in CKAAKN-positive pancreatic cancer cell BxPC-3, which is expected as a promising candidate of MRI contrast enhancement for the early diagnosis of pancreatic cancer.


Assuntos
Adenocarcinoma , Nanopartículas de Magnetita , Nanopartículas , Neoplasias Pancreáticas , Humanos , Polímeros , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Linhagem Celular Tumoral , Nanopartículas de Magnetita/química , Meios de Contraste/química , Polietilenoglicóis/química , Imageamento por Ressonância Magnética/métodos , Peptídeos , Neoplasias Pancreáticas
6.
Int J Mol Sci ; 24(5)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36902488

RESUMO

Sharp eyespot and Fusarium crown rot, mainly caused by soil-borne fungi Rhizoctonia cerealis and Fusarium pseudograminearum, are destructive diseases of major cereal crops including wheat (Triticum aestivum). However, the mechanisms underlying wheat-resistant responses to the two pathogens are largely elusive. In this study, we performed a genome-wide analysis of wall-associated kinase (WAK) family in wheat. As a result, a total of 140 TaWAK (not TaWAKL) candidate genes were identified from the wheat genome, each of which contains an N-terminal signal peptide, a galacturonan binding domain, an EGF-like domain, a calcium binding EGF domain (EGF-Ca), a transmembrane domain, and an intracellular Serine/Threonine protein kinase domain. By analyzing the RNA-sequencing data of wheat inoculated with R. cerealis and F. pseudograminearum, we found that transcript abundance of TaWAK-5D600 (TraesCS5D02G268600) on chromosome 5D was significantly upregulated, and that its upregulated transcript levels in response to both pathogens were higher compared with other TaWAK genes. Importantly, knock-down of TaWAK-5D600 transcript impaired wheat resistance against the fungal pathogens R. cerealis and F. pseudograminearum, and significantly repressed expression of defense-related genes in wheat, TaSERK1, TaMPK3, TaPR1, TaChitinase3, and TaChitinase4. Thus, this study proposes TaWAK-5D600 as a promising gene for improving wheat broad resistance to sharp eyespot and Fusarium crown rot (FCR) in wheat.


Assuntos
Fusarium , Triticum , Triticum/genética , Fusarium/genética , Fator de Crescimento Epidérmico/metabolismo , Cromossomos , Sequência de Bases , Doenças das Plantas/microbiologia
7.
J Integr Plant Biol ; 65(5): 1262-1276, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36534453

RESUMO

Seed dormancy is an important agronomic trait in crops, and plants with low dormancy are prone to preharvest sprouting (PHS) under high-temperature and humid conditions. In this study, we report that the GATA transcription factor TaGATA1 is a positive regulator of seed dormancy by regulating TaABI5 expression in wheat. Our results demonstrate that TaGATA1 overexpression significantly enhances seed dormancy and increases resistance to PHS in wheat. Gene expression patterns, abscisic acid (ABA) response assay, and transcriptome analysis all indicate that TaGATA1 functions through the ABA signaling pathway. The transcript abundance of TaABI5, an essential regulator in the ABA signaling pathway, is significantly elevated in plants overexpressing TaGATA1. Chromatin immunoprecipitation assay (ChIP) and transient expression analysis showed that TaGATA1 binds to the GATA motifs at the promoter of TaABI5 and induces its expression. We also demonstrate that TaGATA1 physically interacts with the putative demethylase TaELF6-A1, the wheat orthologue of Arabidopsis ELF6. ChIP-qPCR analysis showed that H3K27me3 levels significantly decline at the TaABI5 promoter in the TaGATA1-overexpression wheat line and that transient expression of TaELF6-A1 reduces methylation levels at the TaABI5 promoter, increasing TaABI5 expression. These findings reveal a new transcription module, including TaGATA1-TaELF6-A1-TaABI5, which contributes to seed dormancy through the ABA signaling pathway and epigenetic reprogramming at the target site. TaGATA1 could be a candidate gene for improving PHS resistance.


Assuntos
Fatores de Transcrição GATA , Triticum , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição GATA/genética , Regulação da Expressão Gênica de Plantas , Germinação , Dormência de Plantas/genética , Sementes/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triticum/genética , Triticum/metabolismo , Proteínas de Plantas/genética
8.
J Immunol Res ; 2022: 1886083, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36199667

RESUMO

Objectives: Antisynthetase syndrome (ASS) and dermatomyositis (DM) are serious autoimmune diseases, with lungs being the most frequently involved organ and sometimes fatal. This study is aimed at clarifying the role of neutrophil-associated biological markers in suggesting ASS and DM-associated respiratory infections and interstitial lung diseases. Methods: We carried out a retrospective review of the medical records of 46 cases of ASS and DM diagnosed at the Second Hospital of Zhejiang University College of Medicine, between January 2017 and December 2020. Serum myeloperoxidase (MPO), neutrophil elastase (NE), α1 anti-trypsin (AAT), and interleukin-6 (IL-6) were also detected. Results: Gottron's sign is characteristic of dermatomyositis, while polyarthritis is more characteristic of ASS. Pulmonary function is worse in ASS than in DM patients. Patients with ASS and DM had abnormal lymphocyte and neutrophil counts compared to healthy subjects, but not in relation to lung function and rapid progression of interstitial lung disease (RP-ILD). Elevated serum NE, MPO, and IL-6 levels are suggestive of respiratory infections, whereas decreased circulating IL-6 is predictive of RP-ILD. Conclusion: Our study identified the neutrophil-associated biomarkers MPO, NE, and IL-6 as promising indicators with different suggestive roles in respiratory infections and interstitial lung diseases in patients with ASS and DM.


Assuntos
Dermatomiosite , Doenças Pulmonares Intersticiais , Infecções Respiratórias , Humanos , Biomarcadores , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Interleucina-6 , Elastase de Leucócito , Doenças Pulmonares Intersticiais/diagnóstico , Miosite , Neutrófilos , Peroxidase , Infecções Respiratórias/complicações , Estudos Retrospectivos
9.
Orthop Surg ; 14(10): 2757-2765, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36028926

RESUMO

OBJECTIVE: To verify the effect of single-door laminoplasty combined with atlantoaxial fusion in the treatment of symptomatic atlas canal stenosis. METHODS: This is a single-center retrospective analysis. From February 2014 to January 2019, 16 patients (five were females) with an average age of 63.4 years (56-71 years) were enrolled in this study. Patients with compressive cervical myelopathy with CT scan showed an inner sagittal diameter (ISD) of C1 less than 29 mm or C1 canal space available for cord (SAC) of <12 mm were included, while isolated C1 stenosis without myelopathy or isolated C1 stenosis without atlantoaxial subluxation were excluded in this study. All patients underwent continuous heavy-weight skull traction, atlas single-door laminoplasty and atlantoaxial fusion. The differences in the pre- and post-operative inner sagittal diameter, space available for cord, atlas-dens interval (ADI) and compression of the spinal cord were analyzed by using CT and MRI. Functional evaluation was performed by using the Japanese Orthopaedic Association scoring system and the Neck Disability Index scoring system. RESULTS: Single-door laminoplasty provided a full decompression for the spinal cord while retaining the whole posterior arch. No complications were encountered except a superficial wound infection in one patient. At final follow-up, The ADI was significantly reduced from 5.2 ± 1.8 mm to 1.7 ± 0.6 mm after surgery on average (P < 0.05). Average inner sagittal diameter of C1 was increased from 26.3 ± 2.6 mm to 34.9 ± 2.9 mm and the space available for cord was increased from 6 ± 1.7 mm to 17.8 ± 3.6 mm (P < 0.05). Meanwhile, the Japanese Orthopaedic Association (JOA) score of the 16 cases was improved from 11.4 ± 1.8 to 14.1 ± 1.4 on average (P < 0.05). The postoperative neck pain VAS score decreased significantly, from 2.6 ± 1.0 preoperatively to 1.3 ± 0.9 postoperatively (P < 0.05). The influence of neck pain on patient's life was improved from 17.8 ± 3.9 to 13.9 ± 3.3 after surgery (P < 0.05). At the last follow-up, the healing of the hinge fracture and the fusion between atlas and axis were observed in all patients. CONCLUSIONS: Single-door laminoplasty combined with atlantoaxial fusion not only provides enough space for decompression but also offers intact arch for bone grafting, suggesting that it might provide a more feasible method for the correction of symptomatic atlas canal stenosis.


Assuntos
Laminoplastia , Compressão da Medula Espinal , Doenças da Medula Espinal , Idoso , Articulação Atlantoaxial/anormalidades , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Anormalidades Congênitas , Constrição Patológica/cirurgia , Feminino , Humanos , Laminectomia/métodos , Laminoplastia/métodos , Masculino , Pessoa de Meia-Idade , Cervicalgia/cirurgia , Estudos Retrospectivos , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/cirurgia , Doenças da Medula Espinal/cirurgia , Resultado do Tratamento
10.
Plant Biotechnol J ; 20(4): 777-793, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34873799

RESUMO

STAUROSPORINE AND TEMPERATURE SENSITIVE3 (STT3) is a catalytic subunit of oligosaccharyltransferase, which is important for asparagine-linked glycosylation. Sharp eyespot, caused by the necrotrophic fungal pathogen Rhizoctonia cerealis, is a devastating disease of bread wheat. However, the molecular mechanisms underlying wheat defense against R. cerealis are still largely unclear. In this study, we identified TaSTT3a and TaSTT3b, two STT3 subunit genes from wheat and reported their functional roles in wheat defense against R. cerealis and increasing grain weight. The transcript abundance of TaSTT3b-2B was associated with the degree of wheat resistance to R. cerealis and induced by both R. cerealis and exogenous jasmonic acid (JA). Overexpression of TaSTT3b-2B significantly enhanced resistance to R. cerealis, grain weight, and JA content in transgenic wheat subjected to R. cerealis stress, while silencing of TaSTT3b-2B compromised resistance of wheat to R. cerealis. Transcriptomic analysis showed that TaSTT3b-2B affected the expression of a series of defense-related genes and JA biosynthesis-related genes, as well as genes coding starch synthase and sucrose synthase. Application of exogenous JA elevated expression levels of the abovementioned defense- and grain weight-related genes, and rescuing the resistance of TaSTT3b-2B-silenced wheat to R. cerealis, while pretreatment with sodium diethyldithiocarbamate, an inhibitor of JA synthesis, attenuated the TaSTT3b-2B-mediated resistance to R. cerealis, suggesting that TaSTT3b-2B played critical roles in regulating R. cerealis resistance and grain weight via JA biosynthesis. Altogether, this study reveals new functional roles of TaSTT3b-2B in regulating plant innate immunity and grain weight, and illustrates its potential application value for wheat molecular breeding.


Assuntos
Resistência à Doença , Triticum , Resistência à Doença/genética , Grão Comestível/genética , Grão Comestível/metabolismo , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Rhizoctonia , Triticum/metabolismo
11.
J Biomed Mater Res B Appl Biomater ; 110(3): 712-724, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34664385

RESUMO

Despite progress in clinical treatment, microvascular invasion (MVI) remains a major factor for frequent recurrence and metastasis of hepatocellular carcinoma (HCC) after liver resection and surgery. Thus, this study constructed a target nanoplatform (αCD97-USPIO-Au-DDP) with magnetic field/near-infrared (NIR) light response using ultrasmall superparamagnetic iron oxide-gold nanoporous spheres (USPIO-Au) as multifunctional nanocarrier. Anticancer drug cisplatin (DDP) was loaded, and specifically expressed CD97 protein in MVI was taken as the therapeutic target. The αCD97-USPIO-Au-DDP showed favorable photothermal and stable properties under the NIR light at 808 nm wavelength. As suggested by in vitro and in vivo research, this composite nanopreparation could effectively reduce damage to normal organs and showed good biocompatibility. Excellent magnetic targeting function of nanocarrier and modification of αCD97 strengthened accumulation of composite nanodrug in tumor to inhibit tumor growth. This system may have important ramifications for treatment of MVI in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanocompostos , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Campos Magnéticos , Fototerapia
12.
Front Oncol ; 11: 700204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722248

RESUMO

OBJECTIVE: To confirm the diagnostic performance of computed tomography (CT)-based texture analysis (CTTA) and magnetic resonance imaging (MRI)-based texture analysis for grading cartilaginous tumors in long bones and to compare these findings to radiological features. MATERIALS AND METHODS: Twenty-nine patients with enchondromas, 20 with low-grade chondrosarcomas and 16 with high-grade chondrosarcomas were included retrospectively. Clinical and radiological information and 9 histogram features extracted from CT, T1WI, and T2WI were evaluated. Binary logistic regression analysis was performed to determine predictive factors for grading cartilaginous tumors and to establish diagnostic models. Another 26 patients were included to validate each model. Receiver operating characteristic (ROC) curves were generated, and accuracy rate, sensitivity, specificity and positive/negative predictive values (PPV/NPV) were calculated. RESULTS: On imaging, endosteal scalloping, cortical destruction and calcification shape were predictive for grading cartilaginous tumors. For texture analysis, variance, mean, perc.01%, perc.10%, perc.99% and kurtosis were extracted after multivariate analysis. To differentiate benign cartilaginous tumors from low-grade chondrosarcomas, the imaging features model reached the highest accuracy rate (83.7%) and AUC (0.841), with a sensitivity of 75% and specificity of 93.1%. The CTTA feature model best distinguished low-grade and high-grade chondrosarcomas, with accuracies of 71.9%, and 80% in the training and validation groups, respectively; T1-TA and T2-TA could not distinguish them well. We found that the imaging feature model best differentiated benign and malignant cartilaginous tumors, with an accuracy rate of 89.2%, followed by the T1-TA feature model (80.4%). CONCLUSIONS: The imaging feature model and CTTA- or MRI-based texture analysis have the potential to differentiate cartilaginous tumors in long bones by grade. MRI-based texture analysis failed to grade chondrosarcomas.

13.
Front Plant Sci ; 12: 758196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777437

RESUMO

The soil-borne fungi Fusarium pseudograminearum and Rhizoctonia cerealis are the major pathogens for the economically important diseases Fusarium crown rot (FCR) and sharp eyespot of common wheat (Triticum aestivum), respectively. However, there has been no report on the broad resistance of wheat genes against both F. pseudograminearum and R. cerealis. In the current study, we identified TaWAK-6D, a wall-associated kinase (WAK) which is an encoding gene located on chromosome 6D, and demonstrated its broad resistance role in the wheat responses to both F. pseudograminearum and R. cerealis infection. TaWAK-6D transcript induction by F. pseudograminearum and R. cerealis was related to the resistance degree of wheat and the gene expression was significantly induced by exogenous pectin treatment. Silencing of TaWAK-6D compromised wheat resistance to F. pseudograminearum and R. cerealis, and repressed the expression of a serial of wheat defense-related genes. Ectopic expression of TaWAK-6D in Nicotiana benthamiana positively modulated the expression of several defense-related genes. TaWAK-6D protein was determined to localize to the plasma membrane in wheat and N. benthamiana. Collectively, the TaWAK-6D at the plasma membrane mediated the broad resistance responses to both F. pseudograminearum and R. cerealis in wheat at the seedling stage. This study, therefore, concludes that TaWAK-6D is a promising gene for improving wheat broad resistance to FCR and sharp eyespot.

14.
Int J Mol Sci ; 22(21)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34768923

RESUMO

Fusarium head blight (FHB) and sharp eyespot are important diseases of the cereal plants, including bread wheat (Triticum aestivum) and barley. Both diseases are predominately caused by the pathogenic fungi, Fusarium graminearum and Rhizoctonia cerealis. The roles of the wheat-wall-associated kinases (WAKs) in defense against both F. graminearum and R. cerealis have remained largely unknown. This research reports the identification of TaWAK2A-800, a wheat WAK-coding gene located on chromosome 2A, and its functional roles in wheat resistance responses to FHB and sharp eyespot. TaWAK2A-800 transcript abundance was elevated by the early infection of R. cerealis and F. graminearum, or treatment with exogenous chitin. The gene transcript seemed to correspond to the resistance of wheat. Further functional analyses showed that silencing TaWAK2A-800 compromised the resistance of wheat to both FHB (F. graminearum) and sharp eyespot (R. cerealis). Moreover, the silencing reduced the expression levels of six defense-related genes, including the chitin-triggering immune pathway-marker genes, TaCERK1, TaRLCK1B, and TaMPK3. Summarily, TaWAK2A-800 participates positively in the resistance responses to both F. graminearum and R. cerealis, possibly through a chitin-induced pathway in wheat. TaWAK2A-800 will be useful for breeding wheat varieties with resistance to both FHB and sharp eyespot.


Assuntos
Basidiomycota/metabolismo , Resistência à Doença/genética , Fusarium/metabolismo , Doenças das Plantas/microbiologia , Proteínas Quinases/metabolismo , Triticum/microbiologia , Parede Celular/enzimologia , Grão Comestível/microbiologia , Genoma de Planta/genética , Imunidade Inata/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Doenças das Plantas/prevenção & controle , Proteínas Quinases/genética
15.
Biology (Basel) ; 10(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34827115

RESUMO

The fungus F. pseudograminearum can cause the destructive disease Fusarium crown rot (FCR) of wheat, an important staple crop. Functional roles of FCR resistance genes in wheat are largely unknown. In the current research, we characterized the antifungal activity and positive-regulatory function of the cysteine-rich repeat receptor-like kinase TaCRK-7A in the defense against F. pseudograminearum in wheat. Antifungal assays showed that the purified TaCRK-7A protein inhibited the growth of F. pseudograminearum. TaCRK-7A transcript abundance was elevated after F. pseudograminearum attack and was positively related to FCR-resistance levels of wheat cultivars. Intriguingly, knocking down of TaCRK-7A transcript increased susceptibility of wheat to FCR and decreased transcript levels of defense-marker genes in wheat. Furthermore, the transcript abundances of TaCRK-7A and its modulated-defense genes were responsive to exogenous jasmonate treatment. Taken together, these results suggest that TaCRK-7A can directly inhibit F. pseudograminearum growth and mediates FCR-resistance by promoting the expression of wheat defense genes in the jasmonate pathway. Thus, TaCRK-7A is a potential gene resource in FCR-resistant wheat breeding program.

16.
Clin Cancer Res ; 27(23): 6543-6558, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34426437

RESUMO

PURPOSE: There is still no standard nonsurgical regimen for conventional chondrosarcoma (CHS). We aimed to identify whether any CHSs have a favored microenvironment for immunotherapy via multidimensional evaluation of the immunologic characteristics of this tumor. EXPERIMENTAL DESIGN: We obtained 98 newly-diagnosed CHS fresh tumors from several institutions and performed comprehensive analysis of data from CyTOF, whole-exome sequencing, and flow cytometry in 22 cases. Clinical data from immunotherapy responders and nonresponders were compared to explore possible biomarkers of immunotherapy response. Mechanism studies were conducted to interpret the biomarker phenotype. RESULTS: Based on the integrated data of single-cell CyTOF and flow cytometry, the CHS immune-microenvironment phenotypes were classified into three groups: subtype I, the "granulocytic-myeloid-derived suppressor cell (G-MDSC) dominant" cluster, with high number of HLA-DR- CD14- myeloid cells; subtype II, the "immune exhausted" cluster, with high exhausted T-cell and dendritic-cell infiltration; and subtype III, the "immune desert" cluster, with few immune cells. Immune cell-rich subtypes (subtype I and II) were characterized by IDH mutation, pathologic high grade, and peritumoral edema, while subtype I cases were exclusively featured by myxoid transformation. In clinical practice involving 12 individuals who received PD-1 antibody immunotherapy, all of the 3 cases with controlled diseases were retrospectively classified as subtype II. In mechanism, IDH mutation significantly elevated chemokine levels and immune-cell infiltration in immune-inactivated tumors. CONCLUSIONS: This study is the first to provide immune characterization of CHS, representing a major step to precise immunotherapy against this malignancy. Immunotherapy is promising for the "immune exhausted" subtype of patients with CHS.


Assuntos
Condrossarcoma , Células Supressoras Mieloides , Condrossarcoma/genética , Condrossarcoma/terapia , Humanos , Imunoterapia/métodos , Estudos Retrospectivos , Microambiente Tumoral/genética
17.
Int J Mol Sci ; 22(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073183

RESUMO

Sharp eyespot, caused by necrotrophic fungus Rhizoctonia cerealis, is a serious fungal disease in wheat (Triticum aestivum). Certain wall-associated receptor kinases (WAK) mediate resistance to diseases caused by biotrophic/hemibiotrophic pathogens in several plant species. Yet, none of wheat WAK genes with positive effect on the innate immune responses to R. cerealis has been reported. In this study, we identified a WAK gene TaWAK7D, located on chromosome 7D, and showed its positive regulatory role in the defense response to R. cerealis infection in wheat. RNA-seq and qRT-PCR analyses showed that TaWAK7D transcript abundance was elevated in wheat after R. cerealis inoculation and the induction in the stem was the highest among the tested organs. Additionally, TaWAK7D transcript levels were significantly elevated by pectin and chitin treatments. The knock-down of TaWAK7D transcript impaired resistance to R. cerealis and repressed the expression of five pathogenesis-related genes in wheat. The green fluorescent protein signal distribution assays indicated that TaWAK7D localized on the plasma membrane in wheat protoplasts. Thus, TaWAK7D, which is induced by R. cerealis, pectin and chitin stimuli, positively participates in defense responses to R. cerealis through modulating the expression of several pathogenesis-related genes in wheat.


Assuntos
Resistência à Doença , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/microbiologia , Proteínas de Plantas , Proteínas Quinases , Rhizoctonia/crescimento & desenvolvimento , Triticum , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Proteínas Quinases/biossíntese , Proteínas Quinases/genética , Triticum/enzimologia , Triticum/genética , Triticum/microbiologia
19.
Infect Dis Ther ; 10(1): 483-494, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33532909

RESUMO

INTRODUCTION: Since December 2019, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic in China and worldwide. New drugs for the treatment of COVID-19 are in urgent need. Considering the long development time for new drugs, the identification of promising inhibitors from FDA-approved drugs is an imperative and valuable strategy. Recent studies have shown that the S1 and S2 subunits of the spike protein of SARS-CoV-2 utilize human angiotensin-converting enzyme 2 (hACE2) as the receptor to infect human cells. METHODS: We combined molecular docking and surface plasmon resonance (SPR) to identify potential inhibitors for ACE2 from available commercial medicines. We also designed coronavirus pseudoparticles that contain the spike protein assembled onto green fluorescent protein or luciferase reporter gene-carrying vesicular stomatitis virus core particles. RESULTS: We found that thymoquinone, a phytochemical compound obtained from the plant Nigella sativa, is a potential drug candidate. SPR analysis confirmed the binding of thymoquinone to ACE2. We found that thymoquinone can inhibit SARS-CoV-2, SARS-CoV, and NL63 pseudoparticles infecting HEK293-ACE2 cells, with half-maximal inhibitory concentrations of 4.999, 7.598, and 6.019 µM, respectively. The SARS-CoV-2 pseudoparticle inhibition had half-maximal cytotoxic concentration of 35.100 µM and selection index = 7.020. CONCLUSION: Thymoquinone is a potential broad-spectrum inhibitor for the treatment of coronavirus infections.

20.
Medicine (Baltimore) ; 100(2): e24035, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466150

RESUMO

RATIONALE: Contrast-induced encephalopathy (CIE) is a rare complication caused by administration of intravascular contrast media and characterized by acute reversible neurological disturbance. Most of the CIE cases are reported after arterial administration of contrast media such as during cerebral or coronary angiographies, yet only a few articles have reported CIE secondary to intravenous contrast. A case of CIE secondary to intravenous contrast administration is reported here. PATIENT CONCERNS: A 68-year-old man was admitted to our hospital for contrast-enhanced chest computed-tomography (CT) examination due to suspected pulmonary nodules. After CT examination, the patient lost consciousness and experienced a cardiorespiratory arrest. An emergency plain brain CT was done immediately which showed abnormal cortical contrast enhancement and cerebral sulci hyperdensity. DIAGNOSES: After excluding other differential diagnoses such as electrolytes imbalance, hypo/hyperglycemia, cardiogenic pathologies and other neurological emergencies such as cerebral hemorrhage, cerebral infarction, the final diagnosis of CIE was made. INTERVENTIONS: The patient was admitted to the intensive care unit for further management. A series of supportive treatments were arranged. OUTCOMES: Follow-up visits at the outpatient clinic showed no lasting neurological deficits. LESSONS: CIE should be considered as 1 of the differential diagnoses for a patient with acute neurologic symptoms after iodinate contrast administration. Neuroradiological imaging examinations are essential to rule out other etiologies such as acute cerebral infarction or intracranial hemorrhage.


Assuntos
Encefalopatias/induzido quimicamente , Meios de Contraste/efeitos adversos , Parada Cardíaca/induzido quimicamente , Idoso , Angiografia Coronária , Humanos , Masculino , Tomografia Computadorizada por Raios X
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