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1.
BMC Pulm Med ; 24(1): 130, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491484

RESUMO

Bronchopulmonary dysplasia (BPD) is characterized by alveolar dysplasia, and evidence indicates that interferon regulatory factor 4 (IRF4) is involved in the pathogenesis of various inflammatory lung diseases. Nonetheless, the significance and mechanism of IRF4 in BPD remain unelucidated. Consequently, we established a mouse model of BPD through hyperoxia exposure, and ELISA was employed to measure interleukin-17 A (IL-17 A) and interleukin-6 (IL-6) expression levels in lung tissues. Western blotting was adopted to determine the expression of IRF4, surfactant protein C (SP-C), and podoplanin (T1α) in lung tissues. Flow cytometry was utilized for analyzing the percentages of FOXP3+ regulatory T cells (Tregs) and FOXP3+RORγt+ Tregs in CD4+ T cells in lung tissues to clarify the underlying mechanism. Our findings revealed that BPD mice exhibited disordered lung tissue structure, elevated IRF4 expression, decreased SP-C and T1α expression, increased IL-17 A and IL-6 levels, reduced proportion of FOXP3+ Tregs, and increased proportion of FOXP3+RORγt+ Tregs. For the purpose of further elucidating the effect of IRF4 on Treg phenotype switching induced by hyperoxia in lung tissues, we exposed neonatal mice with IRF4 knockout to hyperoxia. These mice exhibited regular lung tissue structure, increased proportion of FOXP3+ Tregs, reduced proportion of FOXP3+RORγt+ Tregs, elevated SP-C and T1α expression, and decreased IL-17 A and IL-6 levels. In conclusion, our findings demonstrate that IRF4-mediated Treg phenotype switching in lung tissues exacerbates alveolar epithelial cell injury under hyperoxia exposure.


Assuntos
Displasia Broncopulmonar , Hiperóxia , Animais , Camundongos , Células Epiteliais Alveolares/patologia , Linfócitos T Reguladores/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Hiperóxia/complicações , Displasia Broncopulmonar/metabolismo , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Fenótipo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo
2.
Int J Mol Sci ; 25(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000057

RESUMO

Toxoplasma gondii, an important opportunistic pathogen, underscores the necessity of developing novel therapeutic drugs and identifying new drug targets. Our findings indicate that the half-maximal inhibitory concentrations (IC50) of KU60019 and CP466722 (abbreviated as KU and CP) against T. gondii are 0.522 µM and 0.702 µM, respectively, with selection indices (SI) of 68 and 10. Treatment with KU and CP affects the in vitro growth of T. gondii, inducing aberrant division in the daughter parasites. Transmission electron microscopy reveals that KU and CP prompt the anomalous division of T. gondii, accompanied by cellular enlargement, nuclear shrinkage, and an increased dense granule density, suggesting potential damage to parasite vesicle transport. Subsequent investigations unveil their ability to modulate the expression of certain secreted proteins and FAS II (type II fatty acid synthesis) in T. gondii, as well as including the dot-like aggregation of the autophagy-related protein ATG8 (autophagy-related protein 8), thereby expediting programmed death. Leveraging DARTS (drug affinity responsive target stability) in conjunction with 4D-Label-free quantitative proteomics technology, we identified seven target proteins binding to KU, implicated in pivotal biological processes such as the fatty acid metabolism, mitochondrial ATP transmission, microtubule formation, and Golgi proteins transport in T. gondii. Molecular docking predicts their good binding affinity. Furthermore, KU has a slight protective effect on mice infected with T. gondii. Elucidating the function of those target proteins and their mechanism of action with ATM kinase inhibitors may potentially enhance the treatment paradigm for toxoplasmosis.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Inibidores de Proteínas Quinases , Toxoplasma , Toxoplasma/efeitos dos fármacos , Toxoplasma/enzimologia , Animais , Camundongos , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Toxoplasmose/tratamento farmacológico , Toxoplasmose/parasitologia , Humanos , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/antagonistas & inibidores , Feminino
3.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473741

RESUMO

Iron is an indispensable nutrient for the survival of Toxoplasma gondii; however, excessive amounts can lead to toxicity. The parasite must overcome the host's "nutritional immunity" barrier and compete with the host for iron. Since T. gondii can infect most nucleated cells, it encounters increased iron stress during parasitism. This study assessed the impact of iron stress, encompassing both iron depletion and iron accumulation, on the growth of T. gondii. Iron accumulation disrupted the redox balance of T. gondii while enhancing the parasite's ability to adhere in high-iron environments. Conversely, iron depletion promoted the differentiation of tachyzoites into bradyzoites. Proteomic analysis further revealed proteins affected by iron depletion and identified the involvement of phosphotyrosyl phosphatase activator proteins in bradyzoite formation.


Assuntos
Parasitos , Toxoplasma , Animais , Toxoplasma/metabolismo , Proteômica , Diferenciação Celular
4.
Eur Radiol ; 33(12): 8936-8947, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37368104

RESUMO

OBJECTIVES: To evaluate the performance of a radiomics nomogram developed based on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) MRI for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: A total of 260 eligible patients were retrospectively enrolled from three hospitals (140, 65, and 55 in training, standardized external, and non-standardized external validation cohort). Radiomics features and image characteristics were extracted from Gd-EOB-DTPA MRI image before hepatectomy for each lesion. In the training cohort, a radiomics nomogram which incorporated the radiomics signature and radiological predictors was developed. The performance of the radiomics nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation. A score (m-score) was constructed to stratify the patients and explored whether it could accurately predict patient who benefit from PA-TACE. RESULTS: A radiomics nomogram integrated with the radiomics signature, max-D(iameter) > 5.1 cm, peritumoral low intensity (PTLI), incomplete capsule, and irregular morphology had favorable discrimination in the training cohort (AUC = 0.982), the standardized external validation cohort (AUC = 0.969), and the non-standardized external validation cohort (AUC = 0.981). Decision curve analysis confirmed the clinical usefulness of the novel radiomics nomogram. The log-rank test revealed that PA-TACE significantly decreased the early recurrence in the high-risk group (p = 0.006) with no significant effect in the low-risk group (p = 0.270). CONCLUSIONS: The novel radiomics nomogram combining the radiomics signature and clinical radiological features achieved preoperative non-invasive MVI risk prediction and patient benefit assessment after PA-TACE, which may help clinicians implement more appropriate interventions. CLINICAL RELEVANCE STATEMENT: Our radiomics nomogram could represent a novel biomarker to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization, which may help clinicians to implement more appropriate interventions and perform individualized precision therapies. KEY POINTS: • The novel radiomics nomogram developed based on Gd-EOB-DTPA MRI achieved preoperative non-invasive MVI risk prediction. • An m-score based on the radiomics nomogram could stratify HCC patients and further identify individuals who may benefit from the PA-TACE. • The radiomics nomogram could help clinicians to implement more appropriate interventions and perform individualized precision therapies.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/irrigação sanguínea , Nomogramas , Estudos Retrospectivos
5.
Gen Comp Endocrinol ; 332: 114180, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36455644

RESUMO

The mammalian melanocortin-5 receptors (MC5Rs) are involved in various functions, including exocrine gland secretion, glucose uptake, adipocyte lipolysis, and immunity. However, the physiological role of fish Mc5r is rarely studied. Melanocortin-2 receptor accessory protein 2 (MRAP2) modulates pharmacological properties of melanocortin receptors. Herein, to lay the foundation for future physiological studies, we cloned the orange-spotted grouper (Epinephelus coioides) mc5r, with a 1008 bp open reading frame and a predicted protein of 334 amino acids. Grouper mc5r had abundant expression in the brain, skin, and kidney. Four ligands could bind to grouper Mc5r and dose-dependently increase intracellular cAMP levels. Grouper Mrap2 did not affect binding affinity or potency of Mc5r; however, grouper Mrap2 decreased cell surface expression and maximal binding of Mc5r. Mrap2 also significantly decreased the maximal response to a superpotent agonist but not the endogenous agonist. This study provided new data on fish Mc5r pharmacology and its regulation by Mrap2.


Assuntos
Bass , Doenças dos Peixes , Animais , Bass/genética , Regulação da Expressão Gênica , Sequência de Aminoácidos , Receptores de Melanocortina/metabolismo , Proteínas de Peixes/metabolismo , Filogenia , Clonagem Molecular , Mamíferos/metabolismo
6.
J Sep Sci ; 46(10): e2200875, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36919985

RESUMO

A method was established for the separation and determination of triadimefon and its metabolite triadimenol enantiomer residues in major complementary fruit puree for infants and young children (banana puree, pineapple puree, and grape puree) by supercritical fluid chromatography. After the samples were extracted with acetonitrile and purified with a solid phase extraction cartridge, Acquity Trefoil CEL2 chiral chromatographic column was adopted for separation, and gradient elution was conducted at the flow rate of 1.0 ml/min under the mobile phase of supercritical carbon dioxide - 0.5% ammonia methanol, the detection wavelength was 220 nm and quantification was conducted with the external standard method. The limits of quantitation of triadimefon and triadimenol enantiomers were both 0.05 mg/kg, the linear ranges were 0.5-50 mg/L, and the linear correlation coefficients were greater than 0.9993. The recoveries in the spiked samples at 0.05, 0.2, and 3.0 mg/kg were from 80.1 to 106%, and the relative standard deviation reached 3.3-7.6%. The method is efficient, rapid, reproducible, and environmentally friendly, enabling accurate analysis of pesticide enantiomers, which can detect the enantiomer residues of triadimefon and its metabolite triadimenol in major complementary fruit puree for infants and young children.


Assuntos
Cromatografia com Fluido Supercrítico , Fungicidas Industriais , Criança , Humanos , Pré-Escolar , Frutas/química , Fungicidas Industriais/análise , Cromatografia com Fluido Supercrítico/métodos , Estereoisomerismo , Cromatografia Líquida de Alta Pressão
7.
Environ Geochem Health ; 45(7): 4193-4202, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36629960

RESUMO

Most studies have focused on the pulmonary toxicity of inhaled PAHs to date; therefore, their hepatotoxic consequences are yet unknown. The main aim of this study is to examine the association between urinary polycyclic aromatic hydrocarbons (PAHs) and liver function parameters among the US population. The data included in this study were from the National Health and Nutritional Examination Survey (NHANES) 2003-2016. Finally, we included 2515 participants from seven cycles of the NHANES. Logistic regression was performed to calculate the association between each PAH and liver function parameters (elevated vs. normal) with odds ratio (OR) and 95% confidence intervals (CIs), along with adjustment for confounding variables. P < 0.05 was considered to indicate a statistically significant difference. All analyses were performed using R software 4.0.1. In the present study, all 2515 individuals were aged ≥ 18 years, 1211 males, and 1304 females. The average age normal was 45.56 ± 20.20, and the elevated was 46.04 ± 19.73 years, respectively. The results of logistic regression indicated that increased 9-hydroxyfluorene (OR = 2.11, 95% CI = [1.52, 2.95], P < 0.001), 2-hydroxyfluorene (OR = 1.61, 95% CI = [1.23, 2.11], P < 0.001), and 3-hydroxyfluorene (OR = 1.54, 95% CI = [1.21, 1.95], P < 0.001) were associated with elevated GGT. In conclusion, 9-hydroxyfluorene is associated with elevated GGT level, and the effect of 9-hydroxyfluorene on GGT is modified by other PAHs, which means that 9-hydroxyfluorene has a greater influence on GGT when other PAHs are increased.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Estudos Transversais , Inquéritos Nutricionais , Biomarcadores , Fígado
8.
FASEB J ; 35(2): e21352, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33543805

RESUMO

Toxoplasma gondii is an apicomplexan parasite, which has three unique secretory organelles: micronemes, rhoptries, and dense granules. Almost all the secreted proteins are transported through the endoplasmic reticulum (ER) and Golgi system to function in their respective destination by accurate targeting and packaging. Glutathione S-transferase (GST) is a supergene family enzyme that has multiple functions, which include regulation of cell proliferation and death signaling pathways, and participation in transportation and metabolism in mammal cells. However, the role of GST in Toxoplasma gondii has not been explained. In this study, we identified three GST proteins in T gondii, of which GST2 acts as a membrane protein that localizes to the Golgi-endosomal system and colocalizes with proteins involved in vesicle transport as well, including synaptobrevin, putative sortilin (VPS10), Rab5 and Rab6, which function as vesicle transport factors. Moreover, the loss of TgGST2 leads to Rab5 and Rab6 distribution of discrete puncta, and incorrect localization and decreased expression of several secretory proteins, and to significantly reduced invasion capacity and virulence to mice. Consistent with its relation to vesicle transport proteins, the distribution of TgGST2 relies on post-Golgi trafficking. Overall, our findings demonstrated that TgGST2 contributes to vesicle trafficking and plays a critical role in parasite lytic cycle.


Assuntos
Glutationa Transferase/metabolismo , Proteínas de Protozoários/metabolismo , Via Secretória , Toxoplasma/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Endossomos/metabolismo , Complexo de Golgi/metabolismo , Transporte Proteico , Proteínas R-SNARE/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab5 de Ligação ao GTP/metabolismo
9.
FASEB J ; 34(10): 13711-13725, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32808330

RESUMO

Toxoplasma gondii is an obligate intracellular apicomplexan parasite that causes lethal diseases in immunocompromised patients. Ubiquitin-proteasome system (UPS) regulates many cellular processes by degrading ubiquitinylated proteins. The UBL-UBA shuttle protein family, which escorts the ubiquitinylated proteins to the proteasome for degradation, are crucial components of UPS. Here, we identified three UBL-UBA shuttle proteins (TGGT1_304680, DNA damage inducible protein 1, DDI1; TGGT1_295340, UV excision repair protein rad23 protein, RAD23; and TGGT1_223680, ubiquitin family protein, DSK2) localized in the cytoplasm and nucleus of T gondii. Deletion of shuttle proteins inhibited parasites growth and resulted in accumulation of ubiquitinylated proteins. Cell division of triple-gene knockout strain was asynchronous. In addition, we found that the retroviral aspartic protease activity of the nonclassical shuttle protein DDI1 was important for the virulence of Toxoplasma in mice. These results showed the critical roles of UBL-UBA shuttle proteins in regulating the degradation of ubiquitinylated proteins and cell division of T gondii.


Assuntos
Divisão Celular , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas de Protozoários/metabolismo , Toxoplasma/metabolismo , Ubiquitinas/metabolismo , Animais , Linhagem Celular , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteólise , Proteínas de Protozoários/genética , Toxoplasma/patogenicidade , Ubiquitinação , Ubiquitinas/genética , Virulência/genética
10.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360709

RESUMO

Toxoplasma gondii (T. gondii) is an important human and veterinary pathogen causing life-threatening disease in immunocompromised patients. The UBL-UBA shuttle protein family are important components of the ubiquitin-proteasome system. Here, we identified a novel UBL-UBA shuttle protein DSK2b that is charactered by an N-terminal ubiquitin-like domain (UBL) and a C-terminal ubiquitin-associated domain (UBA). DSK2b was localized in the cytoplasm and nucleus. The deletion of dsk2b did not affect the degradation of ubiquitinated proteins, parasite growth in vitro or virulence in mice. The double-gene knockout of dsk2b and its paralogs dsk2a (ΔΔdsk2adsk2b) results in a significant accumulation of ubiquitinated proteins and the asynchronous division of T. gondii. The growth of ΔΔdsk2adsk2b was significantly inhibited in vitro, while virulence in mice was not attenuated. In addition, autophagy occurred in the ΔΔdsk2adsk2b, which was speculated to degrade the accumulated ubiquitinated proteins in the parasites. Overall, DSK2b is a novel UBL-UBA shuttle protein contributing to the degradation of ubiquitinated proteins and is important for the synchronous cell division of T. gondii.


Assuntos
Divisão Celular , Proteólise , Proteínas de Protozoários/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Toxoplasma/metabolismo , Ubiquitinação , Animais , Deleção de Genes , Humanos , Camundongos , Proteínas de Protozoários/genética , Receptores Citoplasmáticos e Nucleares/genética , Toxoplasma/genética , Toxoplasma/patogenicidade
11.
Int J Mol Sci ; 22(21)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34769376

RESUMO

Glutaredoxins (GRXs), important components of the intracellular thiol redox system, are involved in multiple cellular processes. In a previous study, we identified five GRXs in the apicomplexan parasite, Neospora caninum. In the present study, we confirmed that the GRXs S14 and C5 are located in the apicoplast, which suggests unique functions for these proteins. Although single-gene deficiency did not affect the growth of parasites, a double knockout (Δgrx S14Δgrx C5) significantly reduced their reproductive capacity. However, there were no significant changes in redox indices (GSH/GSSG ratio, reactive oxygen species and hydroxyl radical levels) in double-knockout parasites, indicating that grx S14 and grx C5 are not essential for maintaining the redox balance in parasite cells. Key amino acid mutations confirmed that the Cys203 of grx S14 and Cys253/256 of grx C5 are important for parasite growth. Based on comparative proteomics, 79 proteins were significantly downregulated in double-knockout parasites, including proteins mainly involved in the electron transport chain, the tricarboxylic acid cycle and protein translation. Collectively, GRX S14 and GRX C5 coordinate the growth of parasites. However, considering their special localization, the unique functions of GRX S14 and GRX C5 need to be further studied.


Assuntos
Apicoplastos/metabolismo , Glutarredoxinas/metabolismo , Glutationa/metabolismo , Neospora/metabolismo , Proteínas de Protozoários/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Glutarredoxinas/genética , Neospora/genética , Neospora/crescimento & desenvolvimento , Oxirredução , Proteínas de Protozoários/genética
12.
Exp Cell Res ; 375(2): 1-9, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30641040

RESUMO

We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) on control and TGF-ß1-exposed rat lung fibroblasts to identify proteins differentially expressed between cell populations. A total of 196 proteins were found to be differentially expressed in response to TGF-ß1 treatment. Guided by these results, we next determined whether similar changes in protein expression were detectable in the rat lung after chronic exposure to silica dust. Of the five proteins selected for further analysis, we found that levels of all proteins were markedly increased in the silica-exposed rat lung, including the proteins for the very low density lipoprotein receptor (VLDLR) and the transmembrane (type I) heparin sulfate proteoglycan called syndecan 2 (SDC2). Because VLDLR and SDC2 have not, to our knowledge, been previously linked to the pathobiology of silicosis, we next examined whether knockdown of either gene altered responses to TGF-ß1 in MRC-5 lung fibroblasts. Interestingly, we found knockdown of either VLDLR or SDC2 dramatically reduced collagen production to TGF-ß1, suggesting that both proteins might play a novel role in myofibroblast biology and pathogenesis of silica-induced pulmonary fibrosis. In summary, our findings suggest that performing LC-MS/MS on TGF-ß1 stimulated lung fibroblasts can uncover novel molecular targets of activated myofibroblasts in silica-exposed lung.


Assuntos
Fibroblastos/metabolismo , Silicose/genética , Transcriptoma , Fator de Crescimento Transformador beta/farmacologia , Animais , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Fibroblastos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Receptores de LDL/genética , Receptores de LDL/metabolismo , Silicose/metabolismo , Sindecana-2/genética , Sindecana-2/metabolismo
13.
Gen Comp Endocrinol ; 285: 113291, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31568758

RESUMO

Melanocortin-1 receptor (MC1R) has important roles in regulating pigmentation and inflammation. Melanocortin receptor accessory protein 2 (MRAP2) modulates trafficking, ligand binding, and signaling of mammalian melanocortin receptors. However, the effect of MRAP2 on fish MC1R has not been extensively studied. Herein, we cloned the orange-spotted grouper (Epinephelus coioides) mc1r, which had a 972 bp open reading frame encoding a putative protein of 323 amino acids. Grouper mc1r was mainly expressed in the brain, skin, testis, spleen, head kidney, and kidney. EcoMC1R showed high constitutive activities in both Gs-cAMP and ERK1/2 pathways, which could be differentially modulated by grouper MRAP2 (EcoMRAP2). Three agonists, including α-melanocyte-stimulating hormone (MSH), ß-MSH, and ACTH, could bind to EcoMC1R and dose-dependently increase intracellular cAMP production. EcoMRAP2 had no effect on the IC50 in binding assay or EC50 in cAMP assay; however, it dose-dependently decreased the cell surface expression and maximal response to the three agonists. EcoMRAP2 increased basal ERK1/2 activation but did not alter α-MSH-stimulated ERK1/2 activation. This study extends the knowledge base of fish MC1R pharmacology and its regulation by MRAP2.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Bass/metabolismo , Proteínas de Peixes/metabolismo , Receptor Tipo 1 de Melanocortina/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Bass/genética , AMP Cíclico/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Humanos , Ligantes , Sistema de Sinalização das MAP Quinases , Filogenia , Receptor Tipo 1 de Melanocortina/química , Receptor Tipo 1 de Melanocortina/genética , Transdução de Sinais/efeitos dos fármacos
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(6): 755-759, 2020 Nov.
Artigo em Zh | MEDLINE | ID: mdl-33236596

RESUMO

OBJECTIVE: This study aimed to investigate the expression level of protein kinase D (PKD) in oral squamous cell carcinoma (OSCC) and its relationship with differentiation of OSCC. METHODS: Sample was collected from 10 healthy control subjects and 40 OSCC confirmed by histopathological diagnosis, and the immunohistochemical staining was adopted to detect the expression of PKDs in OSCC tissues. The proportion of stained cell and staining intensity were evaluated to get a score, which used to analyze the difference among PKD1, PKD2 and PKD3 in various differentiation OSCC tissues. The correlations between the staining score of PKDs and differentiation of OSCC were further analyzed. RESULTS: PKD1 and PKD3 were high expression in OSCC tissues. There were statistical significance among the staining score of PKD1, PKD2 and PKD3 in various differentiation OSCC tissues ( P<0.001). In addition, there was a significantly negative correlation between the staining score of PKD1 and PKD2 with the differentiation of OSCC ( r=-0.574, -0.341, P<0.001). CONCLUSION: In OSCC tissues with different degree of differentiation, there might be some differences among PKDs which play a major role. The expression of PKD1 and PKD2 was correlated with the differentiation of OSCC, the poor differentiation of OSCC, the higher expression of PKD1 and PKD2.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Canais de Cátion TRPP , Diferenciação Celular , Humanos , Proteína Quinase C , Carcinoma de Células Escamosas de Cabeça e Pescoço , Canais de Cátion TRPP/metabolismo
15.
Gen Comp Endocrinol ; 284: 113234, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31398355

RESUMO

Melanocortin-4 receptor (MC4R) and melanocortin receptor accessory protein 2 (MRAP2) play important roles in the melanocortin system, and interaction of MC4R and MRAP2 is suggested to play pivotal role in energy balance of vertebrates. Orange-spotted grouper (Epinephelus coioides) is a widely cultured marine fish with high economic value in Asia. To explore potential interaction between grouper MC4R and MRAP2, herein we cloned grouper mc4r and mrap2. Grouper mc4r consisted of a 981 bp ORF encoding a putative protein of 327 amino acids, while the grouper mrap2 consisted of a 696 bp ORF encoding a putative protein of 232 amino acids. Sequence and phylogenetic analysis revealed that the grouper MC4R and MRAP2 were highly homologous at amino acid levels to several teleost MC4Rs and MRAP2s, respectively. qRT-PCR results showed that both mc4r and mrap2 were expressed primarily in the central nervous system. In the periphery, these genes were expressed more widely in male fish. The cloned grouper MC4R was functional, exhibiting high constitutive activity in cAMP pathway, capable of binding to three peptide agonists and increasing intracellular cAMP production dose-dependently. MRAP2 significantly decreased basal and agonist-stimulated cAMP signaling. MRAP2 also increased basal ERK1/2 activation but decreased ligand-induced stimulation when expressed at high levels. These data will facilitate future investigation of these molecules in regulating diverse physiological processes in orange-spotted grouper.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Bass/metabolismo , Receptor Tipo 4 de Melanocortina/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Bass/genética , AMP Cíclico/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Humanos , Ligantes , Filogenia , Receptor Tipo 4 de Melanocortina/genética
17.
Water Sci Technol ; 72(5): 779-84, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26287837

RESUMO

The presence of microconstituents (MCs) in the environment has become an emerging concern to scientists and engineers. Sorption is one of the important removal mechanisms for MCs in wastewater treatment plants (WWTPs) since there is significant sludge production. The purpose of this study is to explore sorption kinetics and isotherms of MCs onto primary sludge. Three MCs, bisphenol-A (BPA), 17-α-ethinylestradiol (EE2) and triclosan (TCS), were chosen for this study. They are hydrophobic and have low vapor pressure, which makes sorption a potential removal mechanism. Both sorption kinetics and isotherm experiments were conducted using primary sludge collected from a local municipal WWTP. The time to equilibrium was around 7 h for all chosen MCs. A pseudo second-order rate model was better at describing the sorption rate than a pseudo first-order rate model. Linear sorption isotherm models were found to fit the experimental data, and the solid-liquid partitioning coefficients for BPA, EE2 and TCS were 81, 728 and 6,407 L/kg.


Assuntos
Compostos Benzidrílicos/química , Etinilestradiol/química , Fenóis/química , Esgotos/química , Triclosan/química , Poluentes Químicos da Água/química , Adsorção , Cinética , Águas Residuárias
18.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(3): 284-6, 2014 Mar.
Artigo em Zh | MEDLINE | ID: mdl-24758077

RESUMO

OBJECTIVE: To observe the effect of catgut implantation at acupoint on the content of tumor necrosis factor alpha (TNF-alpha), and to explore its mechanism for treatment of ankylosing spondylitis (AS). METHODS: Seventy-four AS patients were randomly assigned to the observation group and the control group by digit random table, 37 in each group. Patients in the control group took Sulfasalazine Enteric-coated Tablet (SECT), 0.5 g each time, three times daily for 3 months. Those in the observation group additionally received catgut implantation at acupoint for 3 months. Changes of visual analogue scale (VAS), Schober test, pillow wall distance, thoracic activity, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and TNF-alpha were compared after 3 months of treatment. RESULTS: There was obvious change in VAS, Schober test, pillow wall distance, thoracic activity, ESR, CRP, and TNF-alpha after treatment in the both groups, showing statistical difference when compared with before treatment (P < 0.05, P < 0.01). The aforesaid indices were obviously improved after treatment in the observation group (P < 0.05, P < 0.01). CONCLUSION: Catgut implantation at acupoint, as an assistant therapy, could significantly improve clinical symptoms and signs, decrease the level of TNF-alpha, and its effect was superior to that of oral SECT administration alone.


Assuntos
Terapia por Acupuntura , Espondilite Anquilosante/sangue , Espondilite Anquilosante/terapia , Fator de Necrose Tumoral alfa/sangue , Pontos de Acupuntura , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Sci Rep ; 14(1): 3692, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355663

RESUMO

The objective of this research is to examine the impact of eccentric training on hamstring flexibility and strength in young dancers during the concluding stages of their foundational dance training program. A total of 24 female, second-year dance students from Hebei Normal University were selected as participants. They were divided into three distinct groups: Nordic hamstring exercise and single-leg deadlift group (NHE&SLD), forward bending exercises and standing leg lift group (FBE&SLL), and a control group (CG). The study was designed around a 6-week training regimen. An isokinetic dynamometer was used to measure seated knee flexor-extensor strength, while electronic goniometry was employed to measure hamstring flexibility in the supine position. Paired sample t-tests were conducted within each group, and one-way analysis of covariance (ANCOVA) was utilized for comparisons between groups. In the NHE&SLD group, significant disparities were observed in both concentric (T = - 5.687, P = 0.001) and eccentric (T = - 3.626, P = 0.008) hamstring strength pre and post-intervention. The pre-intervention dominant leg concentric strength test values significantly influenced the post-intervention outcomes (F = 5.313, P = 0.001, η2 = 0.840). Similarly, the pre-intervention dominant leg eccentric strength test values impacted the post-intervention results (F = 4.689, P = 0.043, η2 = 0.190). Following the intervention, the NHE&SLD group displayed marked changes in the active straight leg raising angle on both left (T = - 4.171, P = 0.004) and right (T = - 6.328, P = 0.001) sides. The FBE&SLL group also revealed significant changes in the active straight leg raising angle on both left (T = - 4.506, P = 0.003) and right (T = - 4.633, P = 0.002) sides following the intervention. The pre-intervention left leg concentric strength test value significantly influenced the post-intervention outcomes (F = 25.067, P = 0.001, η2 = 0.556). Likewise, the pre-intervention right leg eccentric strength test value significantly influenced the post-intervention results (F = 85.338, P = 0.01, η2 = 0.810). Eccentric training can better enhance the flexibility and strength of hamstring muscles in dance students. Traditional stretching training significantly improves the flexibility of the hamstring muscles. Eccentric training has more training benefits than traditional stretching training. It is recommended for dance students to use eccentric training when increasing hamstring flexibility and strength.


Assuntos
Dança , Músculos Isquiossurais , Humanos , Feminino , Músculos Isquiossurais/fisiologia , Força Muscular/fisiologia , Estudantes , Articulação do Joelho/fisiologia
20.
J Pain ; : 104616, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936748

RESUMO

Centrally mediated abdominal pain syndrome (CAPS) has generated a heavy disease burden worldwide. This study aimed to explore the serum exosomal microRNAs as potential diagnostic biomarkers for CAPS. From September 2022 to October 2023, 97 patients with CAPS and 96 healthy subjects were enrolled. Differentially expressed serum exosomal miRNAs between patients with CAPS and healthy controls were identified by high-throughput sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). The Receiver Operating Characteristic (ROC) curves and multivariate logistic regression analysis were used to evaluate the diagnostic value of the serum exosomal miRNAs. MiR-6850-5p, miR-194-5p, miR-199a-3p, miR-4525 which were significantly downregulated in serum exomes of CAPS patients compared to healthy controls which yielded the AUC values of 0.914 (95% CI, 0.873-0.954), 0.767 (95% CI, 0.695-0.839), 0.617 (95% CI, 0.527-0.708) and 0.561 (95% CI, 0.465-0.656), respectively to distinguish CAPS patients from healthy subjects. And AUC of the integration of the above 4 miRNAs was 0.931 (95% CI, 0.896-0.966). Multivariate logistic regression indicated that hsa-miR-6850-5p (OR=0.046; p<0.001), anxiety (OR=7.670; p=0.025) and depression (OR=22.967; p=0.008) were the independent predictors of CAPS. Serum exosomal miR-6850-5p is a promising diagnostic biomarker for CAPS. PERSPECTIVE: This study may be the first to explore serum exosomal miRNAs as a new diagnostic biomarker for CAPS, and the findings may help clinicians to access comprehensive understanding and accurate diagnosis of CAPS.

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