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1.
J Am Chem Soc ; 146(27): 18440-18450, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38949166

RESUMO

Transition metal-catalyzed enantioselective hydroamination of 1,3-dienes provides a direct methodology for the construction of chiral allylamines. So far, all of the reported examples used nucleophilic amines and proceeded with 3,4-regioselectivity. Herein, we describe the first example of nickel-catalyzed enantioselective 1,4-hydroamination of 1,3-dienes using trimethoxysilane and hydroxylamines with a structurally adaptable aromatic spiroketal based chiral diphosphine (SKP) as the ligand, affording a wide array of α-substituted chiral allylamines in high yields with excellent regio- and enantioselectivities. This operationally simple protocol demonstrated a broad substrate scope and excellent functional group compatibility, significantly expanding the chemical space for chiral allylamines. Experimental and DFT studies were performed to elucidate the mechanism and to rationalize the regio- and enantioselectivities of the reaction.

2.
Front Cell Infect Microbiol ; 14: 1356907, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863832

RESUMO

Introduction: Microbial community composition is closely associated with host disease onset and progression, underscoring the importance of understanding host-microbiota dynamics in various health contexts. Methods: In this study, we utilized full-length 16S rRNA gene sequencing to conduct species-level identification of the microorganisms in the oral cavity of a giant panda (Ailuropoda melanoleuca) with oral malignant fibroma. Results: We observed a significant difference between the microbial community of the tumor side and non-tumor side of the oral cavity of the giant panda, with the latter exhibiting higher microbial diversity. The tumor side was dominated by specific microorganisms, such as Fusobacterium simiae, Porphyromonas sp. feline oral taxon 110, Campylobacter sp. feline oral taxon 100, and Neisseria sp. feline oral taxon 078, that have been reported to be associated with tumorigenic processes and periodontal diseases in other organisms. According to the linear discriminant analysis effect size analysis, more than 9 distinct biomarkers were obtained between the tumor side and non-tumor side samples. Furthermore, the Kyoto Encyclopedia of Genes and Genomes analysis revealed that the oral microbiota of the giant panda was significantly associated with genetic information processing and metabolism, particularly cofactor and vitamin, amino acid, and carbohydrate metabolism. Furthermore, a significant bacterial invasion of epithelial cells was predicted in the tumor side. Discussion: This study provides crucial insights into the association between oral microbiota and oral tumors in giant pandas and offers potential biomarkers that may guide future health assessments and preventive strategies for captive and aging giant pandas.


Assuntos
Campylobacter , Fusobacterium , Microbiota , Boca , Porphyromonas , RNA Ribossômico 16S , Ursidae , Ursidae/microbiologia , Animais , RNA Ribossômico 16S/genética , Porphyromonas/genética , Porphyromonas/isolamento & purificação , Porphyromonas/classificação , Campylobacter/genética , Campylobacter/isolamento & purificação , Campylobacter/classificação , Boca/microbiologia , Fusobacterium/genética , Fusobacterium/isolamento & purificação , Fibroma/microbiologia , Fibroma/veterinária , Neisseria/isolamento & purificação , Neisseria/genética , Neisseria/classificação , Neoplasias Bucais/microbiologia , Neoplasias Bucais/veterinária , Neoplasias Bucais/patologia , Filogenia , Análise de Sequência de DNA
3.
Oncogene ; 43(27): 2078-2091, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38760447

RESUMO

The aberrant activation of RAS/RAF/MEK/ERK signaling is important for KIT mutation-mediated tumorigenesis of gastrointestinal stromal tumor (GIST). In this study, we found that inhibition of RAF1 suppresses the activation of both wild-type KIT and primary KIT mutations in GIST, with primary KIT mutations showing greater sensitivity. This suggests a positive feedback loop between KIT and RAF1, wherein RAF1 facilitates KIT signaling. We further demonstrated that RAF1 associates with KIT and the kinase activity of RAF1 is necessary for its contribution to KIT activation. Accordingly, inhibition of RAF1 suppressed cell survival, proliferation, and cell cycle progression in vitro mediated by both wild-type KIT and primary KIT mutations. Inhibition of RAF1 in vivo suppressed GIST growth in a transgenic mouse model carrying germline KIT/V558A mutation, showing a similar treatment efficiency as imatinib, the first-line targeted therapeutic drug of GIST, while the combination use of imatinib and RAF1 inhibitor further suppressed tumor growth. Acquisition of drug-resistant secondary mutation of KIT is a major cause of treatment failure of GIST following targeted therapy. Like wild-type KIT and primary KIT mutations, inhibition of RAF1 suppressed the activation of secondary KIT mutation, and the cell survival, proliferation, cell cycle progression in vitro, and tumor growth in vivo mediated by secondary KIT mutation. However, the activation of secondary KIT mutation is less dependent on RAF1 compared with that of primary KIT mutations. Taken together, our results revealed that RAF1 facilitates KIT signaling and KIT mutation-mediated tumorigenesis of GIST, providing a rationale for further investigation into the use of RAF1 inhibitors alone or in combination with KIT inhibitor in the treatment of GIST, particularly in cases resistant to KIT inhibitors.


Assuntos
Tumores do Estroma Gastrointestinal , Proteínas Proto-Oncogênicas c-kit , Proteínas Proto-Oncogênicas c-raf , Transdução de Sinais , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Animais , Proteínas Proto-Oncogênicas c-raf/metabolismo , Proteínas Proto-Oncogênicas c-raf/genética , Humanos , Camundongos , Camundongos Transgênicos , Proliferação de Células , Linhagem Celular Tumoral , Mutação , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/metabolismo
4.
Int J Pediatr Otorhinolaryngol ; 179: 111906, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492328

RESUMO

BACKGROUND: Previous studies have reported an increasing prevalence of childhood allergic rhinitis in developing countries. There is still a lack of the recent epidemiology of allergic rhinitis among Chinese preschool children. Therefore, this study explored the prevalence of rhinitis symptoms and identified their associations with potential risk factors among children at the age of 3-6 in Shanghai, China. METHODS: Validated International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was adopted to collect information about rhinitis symptoms and potential risk factors. Univariate and multivariate logistic regression analyses were used to assess associations between risk factors and allergic rhinitis and rhinoconjunctivitis. RESULTS: A total of 6183 questionnaires were included in our study. The prevalence of rhinitis ever, current rhinitis, and physician-diagnosed rhinitis were 32.6%, 29.2%, and 14.3%, respectively, while the prevalence of current rhinoconjunctivitis was 11.3%. The higher prevalence was observed in boys than in girls in terms of rhinitis ever, current rhinitis, current rhinoconjunctivitis and doctor-diagnosed rhinitis. Autumn had the highest prevalence among four seasons. In our multivariate logistic regression analyses, history of allergic diseases and paracetamol use in the last year showed positive associations with the increased risk of both current rhinitis and rhinoconjunctivitis, and antibiotic use was an independent significant risk factor only for current rhinitis. Genetic factors, including maternal and paternal rhinitis, asthma, and eczema, were significantly associated with the prevalence of current rhinitis. Similar associations were seen between these factors and current rhinoconjunctivitis, except for paternal eczema. Among environmental factors, smoking exposure at home, heavy truck traffic in home's street, floor heating system were independent risk factors for both current rhinitis and rhinoconjunctivitis in the adjusted model, while cleaning the house less than once a week was only associated with current rhinitis. CONCLUSION: The prevalence of current rhinitis was 29.2% among children aged 3-6 in Shanghai, China. Sex differences and seasonal variations were observed in the prevalence of rhinitis symptoms. The identified risk factors would provide a basis for policy makers and medical experts to take intervention measures to prevent allergic rhinitis and rhinoconjunctivitis.


Assuntos
Asma , Conjuntivite Alérgica , Eczema , Rinite Alérgica , Rinite , Humanos , Feminino , Pré-Escolar , Masculino , Conjuntivite Alérgica/epidemiologia , Conjuntivite Alérgica/etiologia , China/epidemiologia , Rinite/complicações , Fatores de Risco , Eczema/epidemiologia , Rinite Alérgica/epidemiologia , Rinite Alérgica/complicações , Asma/complicações , Inquéritos e Questionários , Prevalência
5.
Adv Sci (Weinh) ; 11(14): e2307920, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308196

RESUMO

Therapeutic cancer vaccines fail to produce satisfactory outcomes against solid tumors since vaccine-induced anti-tumor immunity is significantly hampered by immunosuppression. Generating an in situ cancer vaccine targeting immunological cold tumor microenvironment (TME) appears attractive. Here, a type of free-field based whole-body ultrasound (US)-driven nanovaccines are constructed, named G5-CHC-R, by conjugating the sonosensitizer, Chenghai chlorin (CHC) and the immunomodulator, resiquimod (R848) on top of a super small-sized dendrimeric nanoscaffold. Once entering tumors, R848 can be cleaved from a hypoxia-sensitive linker, thus modifying the TME via converting macrophage phenotypes. The animals bearing orthotopic pancreatic cancer with intestinal metastasis and breast cancer with lung metastasis are treated with G5-CHC-R under a free-field based whole-body US system. Benefit from the deep penetration capacity and highly spatiotemporal selectiveness, G5-CHC-R triggered by US represented a superior alternative for noninvasive irradiation of deep-seated tumors and magnification of local immune responses via driving mass release of tumor antigens and "cold-warm-hot" three-state transformation of TME. In addition to irradiating primary tumors, a robust adaptive anti-tumor immunity is potentiated, leading to successful induction of systemic tumor suppression. The sono-nanovaccines with good biocompatibility posed wide applicability to a broad spectrum of tumors, revealing immeasurable potential for translational research in oncology.


Assuntos
Vacinas Anticâncer , Neoplasias , Animais , Nanovacinas , Ultrassonografia , Imunidade Adaptativa , Adjuvantes Imunológicos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia
6.
Plant Physiol Biochem ; 204: 108122, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37939500

RESUMO

Exploring the responses of root morphology and its physiological mechanisms under drought stress is significant for further improving water and nutrient absorption in roots. Here, we simulated drought through hydroponics combined with PEG treatments in tobacco to characterize the changes in tobacco root architecture. Our results showed the total root length, first lateral root number, and first lateral root length were significantly reduced upon increasing drought severity, but the average root diameter and secondary lateral root density increased under certain drought conditions. The change of auxin content in roots under drought stress was correlated with the root diameter and second lateral root density responses. Exogenous addition of the auxin analog (NAA) and the auxin transport inhibitor (NPA), as well as DR5:GUS staining experiments further demonstrated that auxin participated in this physiological process. Meanwhile, brassinolide (BR) exhibited a similar trend. Exogenous addition of BR (EBR) and the BR synthesis inhibitor BRZ experiments demonstrated that BR may participate upstream of auxin under drought stress. PEG treatment significantly up-regulated NtBRI1 at 9-24 h, and promoted the up-regulation of NtBSK2 and NtBSK3 at 48 h and 24 h, respectively, these genes may contribute to the change in root morphology under drought stress. This study shows that auxin and BR are involved in the changes in root morphology in tobacco exposed to drought stress. The elucidation of the molecular mechanism at play thus represents a future target for breeding drought-tolerant tobacco varieties.


Assuntos
Secas , Nicotiana , Melhoramento Vegetal , Ácidos Indolacéticos/farmacologia , Transporte Biológico , Raízes de Plantas
7.
Org Lett ; 25(35): 6577-6581, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37646423

RESUMO

A Ni-catalyzed enantioselective hydroamination of vinylarenes has been developed, affording a wide variety of α-branched chiral alkylamines in good yields with exclusive Markovnikov regioselectivity and excellent enantioselectivity. The SKP ligand was found to be crucial to both the reactivity enhancement and enantiocontrol of the reaction. The synthetic utility of the protocol was exemplified in a gram-scale reaction and late-stage modification of medicinally relevant molecules. The deuterium-labeling experiment revealed that the irreversible hydronickelation of vinylarenes is most likely the enantioselectivity-determining step.

8.
J Cardiovasc Pharmacol ; 82(5): 375-388, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37643027

RESUMO

ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) is highly prevalent, accounting for 50% of all heart failure patients, and is associated with significant mortality. Sodium-glucose cotransporter subtype inhibitor (SGLT2i) is recommended in the AHA and ESC guidelines for the treatment of HFpEF, but the mechanism of SGLT2i to prevent and treat cardiac remodeling and dysfunction is currently unknown, hindering the understanding of the pathophysiology of HFpEF and the development of novel therapeutics. HFpEF model was induced by a high-fat diet (60% calories from lard) + N [w] -nitro- l -arginine methyl ester ( l -NAME-0.5 g/L) (2 Hit) in male Sprague Dawley rats to effectively recapture the myriad phenotype of HFpEF. This study's results showed that administration of dapagliflozin (DAPA, SGLT2 inhibitor) significantly limited the 2-Hit-induced cardiomyocyte hypertrophy, apoptosis, inflammation, oxidative stress, and fibrosis. It also improved cardiac diastolic and systolic dysfunction in a late-stage progression of HFpEF. Mechanistically, DAPA influences energy metabolism associated with fatty acid intake and mitochondrial dysfunction in HFpEF by increasing ß-hydroxybutyric acid (ß-OHB) levels, directing the activation of citrate synthase, reducing acetyl coenzyme A (acetyl-CoA) pools, modulating adenosine 5'-triphosphate production, and increasing the expression of mitochondrial oxidative phosphorylation system complexes I-V. In addition, following clinical DAPA therapy, the blood levels of ß-OHB and citrate synthase increased and the levels of acetyl-CoA in the blood of HFpEF patients decreased. SGLT2i plays a beneficial role in the prevention and treatment of cardiac remodeling and dysfunction in HFpEF model by attenuating cardiometabolic dysregulation.


Assuntos
Insuficiência Cardíaca , Humanos , Ratos , Animais , Masculino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/metabolismo , Ácido 3-Hidroxibutírico/uso terapêutico , Citrato (si)-Sintase , Volume Sistólico/fisiologia , Remodelação Ventricular , Acetilcoenzima A/uso terapêutico , Ratos Sprague-Dawley
9.
Int J Gen Med ; 16: 1279-1294, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37077765

RESUMO

Background: MicroRNAs influence the growth and metastasis of breast cancer (BC) by regulating their target genes. Our study aims to screen and identify miRNAs that are closely related to the development of breast cancer, and explore the role of these miRNAs and their target genes in breast cancer. Methods: Bioinformatics tools were applied to screen breast cancer-associated miRNAs and predict their potential target genes. Serum miRNAs were measured using RT-PCR. The correlation between miRNA expression and different clinicopathological features of BC patients was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. GEPIA, Kaplan-Meier Plotter, TIMER, and TISIDB databases were used to validate the expression levels and their prognostic value, as well as their target gene associated with immune infiltrating cells and immune checkpoints. Results: Breast cancer-associated serum miR-338-3p and miR-501-3p were screened and verified for the first time. Serum miR-501-3p was elevated in BC and was closely linked to the ki-67 index and histological grade. CDKN2C, as a potential target gene of miR-501-3p, was enriched in the cGMP-PKG signaling pathway. Serum miR-338-3p was reduced in BC and was strongly linked to lymph node metastasis and histological grading. ACTR2, CDH1, COL1A1, RBBP5, RRM1, and TPM3, as potential target genes of miR-338-3p, were enriched in MAPK, PI3K-Akt, and RAS signaling pathways. These target genes were found to be linked to breast cancer prognosis, immune infiltrating cells, and immune checkpoint inhibitors. Analysis of ROC curve showed that serum miR-501-3p combined with serum miR-338-3p had a high diagnostic value in breast cancer (AUC: 0.89, 95% CI: 0.821-0.958). Conclusion: Serum miR-501-3p combined with serum miR-338-3p show obvious clinical significance in the diagnosis and prognosis of breast cancer, which suggests that they may act as novel diagnostic biomarkers for breast cancer.

10.
Int J Mol Sci ; 23(19)2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36233337

RESUMO

Microsporum gypseum causes dermatomycoses in giant pandas (Ailuropoda melanoleuca). This study aimed to investigate the immune response of M. gypseum following deep infection. The degree of damage to the heart, liver, spleen, lungs, and kidneys was evaluated using tissue fungal load, organ index, and histopathological methods. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) detected the mRNA expression of receptors and cytokines in the lung, and immunofluorescence staining and flow cytometry, were used to assess immune cells in the lung. The results indicated that conidia mainly colonized the lungs and caused serious injury with M. gypseum infection. Furthermore, dectin-1, TLR-2, and TLR-4 played a role in recognizing M. gypseum cells. Numerous inflammatory cells, mainly macrophages, dendritic cells, polymorphonuclear neutrophils, and inflammatory cytokines (TGF-ß, TNF-α, IL-1ß, IL-6, IL-10, IL-12, and IL-23), were activated in the early stages of infection. With the high expression of IL-22, IL-17A, and IL-17F, the Th17 pathway exerted an adaptive immune response to M. gypseum infection. These results can potentially aid in the diagnosis and treatment of diseases caused by M. gypseum in giant pandas.


Assuntos
Imunidade Adaptativa , Interleucina-17 , Microsporum , Células Th17 , Ursidae , Animais , Arthrodermataceae , Citocinas/genética , Inflamação , Interleucina-10 , Interleucina-12 , Interleucina-23 , Interleucina-6 , RNA Mensageiro/genética , Células Th17/imunologia , Receptor 2 Toll-Like , Receptor 4 Toll-Like , Fator de Crescimento Transformador beta , Fator de Necrose Tumoral alfa , Ursidae/genética , Ursidae/imunologia
11.
Mol Plant Pathol ; 23(12): 1737-1750, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094814

RESUMO

Tobacco black shank caused by Phytophthora nicotianae is a serious disease in tobacco cultivation. We found that naringenin is a key factor that causes different sensitivity to P. nicotianae between resistant and susceptible tobacco. The level of basal flavonoids in resistant tobacco was distinct from that in susceptible tobacco. Of all flavonoids with different content, naringenin showed the best antimicrobial activity against mycelial growth and sporangia production of P. nicotianae in vitro. However, naringenin showed very low or no antimicrobial activity to other plant pathogens. We found that naringenin induced not only the accumulation of reactive oxygen species, but also the expression of salicylic acid biosynthesis-related genes. Naringenin induced the expression of the basal pathogen resistance gene PR1 and the SAR8.2 gene that contributes to plant resistance to P. nicotianae. We then interfered with the expression of the chalcone synthase (NtCHS) gene, the key gene of the naringenin synthesis pathway, to inhibit naringenin biosynthesis. NtCHS-RNAi rendered tobacco highly sensitive to P. nicotianae, but there was no change in susceptibility to another plant pathogen, Ralstonia solanacearum. Finally, exogenous application of naringenin on susceptible tobacco enhanced resistance to P. nicotianae and naringenin was very stable in this environment. Our findings revealed that naringenin plays a core role in the defence against P. nicotianae and expanded the possibilities for the application of plant secondary metabolites in the control of P. nicotianae.


Assuntos
Phytophthora , Phytophthora/genética , Nicotiana/genética , Doenças das Plantas/genética , Flavonoides
12.
JCI Insight ; 7(10)2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35439169

RESUMO

Systemic therapies for pancreatic ductal adenocarcinoma (PDAC) remain unsatisfactory. Clinical prognosis is particularly poor for tumor subtypes with activating aberrations in the MYC pathway, creating an urgent need for novel therapeutic targets. To unbiasedly find MYC-associated epigenetic dependencies, we conducted a drug screen in pancreatic cancer cell lines. Here, we found that protein arginine N-methyltransferase 5 (PRMT5) inhibitors triggered an MYC-associated dependency. In human and murine PDACs, a robust connection of MYC and PRMT5 was detected. By the use of gain- and loss-of-function models, we confirmed the increased efficacy of PRMT5 inhibitors in MYC-deregulated PDACs. Although inhibition of PRMT5 was inducing DNA damage and arresting PDAC cells in the G2/M phase of the cell cycle, apoptotic cell death was executed predominantly in cells with high MYC expression. Experiments in primary patient-derived PDAC models demonstrated the existence of a highly PRMT5 inhibitor-sensitive subtype. Our work suggests developing PRMT5 inhibitor-based therapies for PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Detecção Precoce de Câncer , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Epigênese Genética , Humanos , Camundongos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias Pancreáticas
13.
Mol Pharm ; 19(2): 584-591, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-34982563

RESUMO

Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a ß-amyloid-specific radiotracer, [18F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [18F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [18F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [18F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [18F]AV-45 uptake. Postoperative histopathological analysis confirmed the [18F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [18F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [18F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Glândula Tireoide , Fluordesoxiglucose F18 , Humanos , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
14.
Chemistry ; 27(64): 15903-15907, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34506052

RESUMO

An efficient nickel-catalyzed regioselective hydroarylation of 1,3-dienes with aryl halides and a silane has been developed, affording a range of allylic arenes in good to excellent yields under mild conditions. This method exhibits broad substrate scope, and excellent functional group tolerance. Late-stage modification of complex architectures was demonstrated.

15.
FASEB J ; 34(9): 12726-12738, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32713114

RESUMO

The proto-oncogene ets1 is highly expressed in the pre-migratory and migratory neural crest (NC), and has been implicated in the delamination and migration of the NC cells. To identify the downstream target genes of Ets1 in this process, we did RNA sequencing (RNA-Seq) on wild-type and ets1 mutant X. tropicalis embryos. A list of genes with significantly differential expression was obtained by analyzing the RNA-Seq data. We validated the RNA-Seq data by quantitative PCR, and examined the expression pattern of the genes identified from this assay with whole mount in situ hybridization. A majority of the identified genes showed expression in migrating NC. Among them, the expression of microseminoprotein beta gene 3 (msmb3) was positively regulated by Ets1 in both X. laevis and X. tropicalis. Knockdown of msmb3 with antisense morpholino oligonucleotides or disruption of msmb3 by CRISPR/Cas9 both impaired the migratory streams of NC. Our study identified msmb3 as an Ets1 target gene and uncovered its function in maintaining neural crest migration pattern.


Assuntos
Embrião não Mamífero/citologia , Crista Neural/citologia , Proteínas Secretadas pela Próstata/fisiologia , Proteína Proto-Oncogênica c-ets-1/fisiologia , Xenopus/embriologia , Animais , Movimento Celular , Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Proto-Oncogene Mas , RNA-Seq
16.
Cell Tissue Res ; 381(3): 493-508, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32607799

RESUMO

Dab2 is an adaptor protein and a tumor suppressor. Our previous study has found that Dab2 was expressed in early differentiating skeletal muscles in mouse embryos. In this study, we determined the role of Dab2 in the skeletal muscle differentiation using C2C12 myoblasts in vitro and Xenopus laevis embryos in vivo. The expression of Dab2 was increased in C2C12 myoblasts during the formation of myotubes in vitro. Knockdown of Dab2 expression in C2C12 myoblasts resulted in a reduction of myotube formation, whereas the myotube formation was enhanced upon overexpression of Dab2. Re-expression of Dab2 in C2C12 myoblasts with downregulated expression of Dab2 restored their capacity to form myotubes. Microarray profiling and subsequent network analyses on the 155 differentially expressed genes after Dab2 knockdown showed that Mef2c was an important myogenic transcription factor regulated by Dab2 through the p38 MAPK pathway. It was also involved in other pathways that are associated with muscular development and functions. In Xenopus embryos developed in vivo, XDab2 was expressed in the myotome of somites where various myogenic markers were also expressed. Knockdown of XDab2 expression with antisense morpholinos downregulated the expression of myogenic markers in somites. In conclusion, this study is the first to provide solid evidence to show that Dab2 is a positive regulator of the early myoblast differentiation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Mioblastos/metabolismo , Animais , Anuros , Diferenciação Celular , Humanos , Camundongos , Transfecção
17.
Arch Biochem Biophys ; 684: 108334, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32173334

RESUMO

Emerging evidence shows that histone modification and its related regulators are involved in the progression and chemoresistance of ovarian cancer (OC) cells. Our present study found that the expression of Jumonji C domain-containing 2A (JMJD2A), while not JMJD2B or JMJD2C, is increased in OC cells and tissues as compared with that in their corresponding controls. Knockdown of JMJD2A can decrease proliferation while increase cisplatin (CDDP) sensitivity of OC cells. By screening the expression of cytokines involved in the progression of ovarian cancer, we found that knockdown of JMJD2A can inhibit the expression of interleukin-6 (IL-6) and IL-8 in ovarian cancer cells. Recombinant IL-6 (rIL-6) and rIL-8 can attenuate si-JMJD2A-suppressed malignancy of OC cells. Mechanistically, JMJD2A can directly bind with the promoter of IL-6 to trigger its transcription. For IL-8, JMJD2A can increase it mRNA stability in OC cells. Collectively, we revealed that JMJD2A can trigger the malignancy of OC cells via upregulation of IL-6 and IL-8. It suggested that JMJD2A might be a potential target for OC treatment and therapy.


Assuntos
Interleucina-6/metabolismo , Interleucina-8/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Interleucina-6/genética , Interleucina-8/genética , Histona Desmetilases com o Domínio Jumonji/genética , Estabilidade de RNA/genética , RNA Mensageiro/metabolismo , Transcrição Gênica/fisiologia , Regulação para Cima
18.
Braz. j. med. biol. res ; 53(12): e9487, 2020. tab, graf
Artigo em Inglês | LILACS, Coleciona SUS | ID: biblio-1132506

RESUMO

This study aimed to explore the association between serum non-high-density lipoprotein cholesterol (non-HDL-C) and cognitive dysfunction risk in patients with acute ischemic stroke (AIS). This cross-sectional study enrolled 583 AIS patients. Biochemical markers and lipid profile were collected after admission. AIS patients were classified into high group (non-HDL-C ≥3.4 mM) and normal group (non-HDL-C <3.4 mM). Mini-Mental State Examination scale (MMSE), Montreal Cognitive Assessment scale (MoCA), Activities of Daily Living (ADL) scale, Neuropsychiatric Inventory (NPI), and Hamilton Depression scale 21 version (HAMD-21) were applied on the third day after admission. Compared with the control group, patients of the high group had higher body mass index and higher frequency of intracranial artery stenosis, and exhibited higher levels of non-HDL-C, total cholesterol, triglycerides, low-density lipoprotein cholesterol, homocysteine, fasting blood glucose, and glycosylated hemoglobin (HbA1c), and lower levels of high-density lipoprotein cholesterol (all P<0.05). Compared with the control group, patients of the high group had significantly lower MMSE and MoCA scores (MMSE: 26.01±4.17 vs 23.12±4.73, P<0.001; MoCA: 22.28±5.28 vs 20.25±5.87, P<0.001) and higher scores on the NPI and HAMD-21 (both P<0.001). MMSE (r=-0.306, P<0.001) and MoCA scores (r=-0.251, P<0.001) were negatively associated with non-HDL-C level. Multivariate regression analysis revealed that non-HDL-C level (OR=1.361, 95%CI: 1.059-1.729, P=0.016) was independently associated with the presence of cognitive dysfunction after adjusting for confounding factors. High serum non-HDL-C level might significantly increase the risk of cognitive dysfunction after AIS.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Isquemia Encefálica/complicações , Disfunção Cognitiva/etiologia , Atividades Cotidianas , Estudos Transversais , Fatores de Risco , AVC Isquêmico/complicações , HDL-Colesterol
19.
Langmuir ; 35(16): 5617-5625, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30942585

RESUMO

Nanostructures and nanomaterials based on peptide self-assembly have attracted tremendous interests due to the functionalities of peptide molecules. Furthermore, the self-assembled peptide nanostructures are also adopted to fabricate nanomaterials and nanodevices. In this work, the intramolecular folding and self-assembly of a ß-hairpin peptide CBHH were first studied under the regulation of platinum ion. And then, platinum nanostructures were synthesized through the reduction of platinum ions templated with peptide self-assemblies. The results of circular dichroism spectroscopy, UV-vis spectroscopy, isothermal titration calorimetry, and atomic force microscopy observation showed that platinum ions could promote the conversion of peptide CBHH secondary structure from a random coil to a ß-sheet through coordination with histidine residues. Platinum nanostructures including nanorods and one dimensionally aligned nanorods were synthesized through in situ reduction with CBHH self-assembled nanofiber as the templates. And the synthesized platinum nanostructures showed excellent electrocatalytic activities.


Assuntos
Nanoestruturas/química , Peptídeos/síntese química , Platina/química , Adsorção , Íons/química , Tamanho da Partícula , Peptídeos/química , Estrutura Secundária de Proteína , Propriedades de Superfície
20.
BMC Vet Res ; 14(1): 311, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30314476

RESUMO

BACKGROUND: Ovarian cancer is diagnosed clinically by detecting ovarian cancer-related factors and markers. Here, we report a case of giant panda ovarian tumor metastasis with a combination of clinical and histopathological diagnosis. CASE PRESENTATION: Histopathological studies revealed severe lesions and tumor cells in the ovaries, lungs, spleen, kidneys and perianal tissue. Immunohistochemistry staining showed that the ovarian cancer markers B7-H4, CA125, and HE4 were highly expressed in the lungs, kidneys, spleen, ovaries and perianal tissue. Tumor marker tests detected significantly high levels of AFP in serum. CONCLUSION: Clinical biomarkers combined with histopathology can provide a more accurate diagnosis of ovarian cancer metastasis and identification of ovarian cancer types than either method alone. The giant panda's death may be due to granulosa cell tumor and theca cell tumor metastasis causing multiple organ dysfunction or even failure.


Assuntos
Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Ursidae , Animais , Biomarcadores Tumorais/análise , Feminino , Imuno-Histoquímica , Metástase Neoplásica
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