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1.
J Med Chem ; 67(10): 7836-7858, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38695063

RESUMO

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax's limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large B-cell lymphomas) and multiple recurrent Bcl-2 mutations (e.g., G101V) have been reported to mediate resistance to venetoclax after long-term treatment. Herein, we described novel Bcl-2 inhibitors with increased potency for both wild-type (WT) and mutant Bcl-2. Comprehensive structure optimization led to the clinical candidate BGB-11417 (compound 12e, sonrotoclax), which exhibits strong in vitro and in vivo inhibitory activity against both WT Bcl-2 and the G101V mutant, as well as excellent selectivity over Bcl-xL without obvious cytochrome P450 inhibition. Currently, BGB-11417 is undergoing phase II/III clinical assessments as monotherapy and combination treatment.


Assuntos
Antineoplásicos , Mutação , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Humanos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Camundongos , Linhagem Celular Tumoral , Sulfonamidas/farmacologia , Sulfonamidas/química , Ratos , Descoberta de Drogas
2.
J Hazard Mater ; 472: 134485, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38701725

RESUMO

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic persistent organic pollutant (POP) that can induce DNA damage within cells. Although oxidative stress is one of the primary mechanisms causing DNA damage, its role in the process of TCDD-induced DNA damage remains unclear. In this study, the TCDD-induced production of reactive oxygen species (ROS) and the occurrence of DNA damage at the AP site were monitored simultaneously. Further investigation revealed that TCDD impaired the activities of superoxide dismutase (SOD) and catalase (CAT), compromising the cellular antioxidant defense system. Consequently, this led to an increase in the production of O2.- and NO, thus inducing DNA damage at the AP site under oxidative stress. Our findings were further substantiated by the upregulation of key genes in the base excision repair (BER) pathway and the absence of DNA AP site damage after inhibiting O2.- and NO. In addition, transcriptome sequencing revealed that TCDD induces DNA damage by upregulating genes associated with oxidative stress in the mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), and breast cancer pathways. This study provides important insights into the toxicity mechanisms of TCDD.


Assuntos
Dano ao DNA , Estresse Oxidativo , Dibenzodioxinas Policloradas , Espécies Reativas de Oxigênio , Dibenzodioxinas Policloradas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Catalase/metabolismo , Superóxido Dismutase/metabolismo , Reparo do DNA/efeitos dos fármacos , Humanos , Poluentes Ambientais/toxicidade
3.
Cancer Nurs ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598755

RESUMO

BACKGROUND: Demoralization is a psychological syndrome that is highly prevalent in patients with cancer and detrimental to individuals' physical and mental health. To explore effective intervention, we first determined the relationships between locus of control, coping strategies, symptom burden, and demoralization. OBJECTIVE: The aim of this study was to determine the relationship between symptom burden, locus of control, coping strategies, and demoralization in patients with cancer. METHODS: In this descriptive-correlational study, 273 valid patients were selected with convenience sampling method from a hospital in China. Data were collected using the Chinese version of the M.D. Anderson Symptom Inventory, the Chinese version of the Multidimensional Health Locus of Control Scale, the Chinese version of the Medical Coping Modes Questionnaire, and the Mandarin version of the Demoralization Scale. Data were analyzed using descriptive and inferential statistics using SPSS and AMOS. RESULTS: A total of 115 patients (42.12%) experienced clinical demoralization (Mandarin version of the Demoralization Scale > 30). Symptom burden (ß = 0.295, P < .001), confrontation (ß = -0.117, P = .028), and resignation (ß = 0.456, P < .001) had direct effects on demoralization. Symptom burden also had an indirect effect on demoralization through the mediating role of resignation (ß = 0.026, P = .002). Meanwhile, locus of control can affect demoralization entirely through the indirect mediating role of coping strategies (chance locus of control via resignation [ß = 0.138, P < .01], powerful locus of control via confrontation [ß = -0.017, P < .05]). CONCLUSIONS: Symptom burden affects demoralization not only directly but also indirectly. Coping strategies play an important mediating role between symptom burden, locus of control, and demoralization in patients with cancer. IMPLICATIONS FOR PRACTICE: It is urgent to screen demoralization and identify patients with high symptom burden, maladaptive locus of control, or coping strategies. For the patients targeted, a more comprehensive and systematic approach to symptom management and more appropriate guidance related to adaptive coping strategies are needed.

4.
Front Immunol ; 15: 1331610, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449859

RESUMO

Objectives: The systemic immune-inflammation index (SII), a novel and systematic inflammatory biomarker that is associated with chronic kidney disease (CKD), has not received much attention. This study aimed to investigate the relationship between SII and CKD in the United States (U.S.) population. Methods: Our study ultimately included a nationally representative sample of 10,787 adults who participated in the 2007-2018 National Health and Nutrition Examination Survey. Weighted multivariate logistic regression was used to assess the correlation between SII and CKD, and a restricted cubic spline (RCS) model was subsequently used to explore the non-linear relationship between SII and CKD. Subgroup analyses were performed to further the effects of other covariates on the relationship between SII and CKD. Results: Following confounder adjustment, a higher SII was related to the incidence of CKD (OR =1.36; 95% CI, 1.07-1.73; p =0.01), as validated by multivariable logistic regression. The RCS curve revealed a non-linear positive correlation between SII/1000 and CKD incidence (p for non-linear =0.0206). Additionally, subgroup analysis confirmed a stronger correlation for male participants (OR =2.628; 95% CI, 1.829-3.776) than for female participants (OR =1.733; 95% CI, 1.379-2.178) (p for interaction =0.046). Conclusions: SII is positively associated with the incidence of CKD among U.S. adults, especially in males. However, further studies are needed to confirm our findings and explore the causal factors that can contribute to the prevention and treatment of CKD.


Assuntos
Inflamação , Insuficiência Renal Crônica , Adulto , Humanos , Feminino , Masculino , Inquéritos Nutricionais , Inflamação/epidemiologia , Insuficiência Renal Crônica/epidemiologia
5.
Blood ; 143(18): 1825-1836, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38211332

RESUMO

ABSTRACT: Venetoclax, the first-generation inhibitor of the apoptosis regulator B-cell lymphoma 2 (BCL2), disrupts the interaction between BCL2 and proapoptotic proteins, promoting the apoptosis in malignant cells. Venetoclax is the mainstay of therapy for relapsed chronic lymphocytic leukemia and is under investigation in multiple clinical trials for the treatment of various cancers. Although venetoclax treatment can result in high rates of durable remission, relapse has been widely observed, indicating the emergence of drug resistance. The G101V mutation in BCL2 is frequently observed in patients who relapsed treated with venetoclax and sufficient to confer resistance to venetoclax by interfering with compound binding. Therefore, the development of next-generation BCL2 inhibitors to overcome drug resistance is urgently needed. In this study, we discovered that sonrotoclax, a potent and selective BCL2 inhibitor, demonstrates stronger cytotoxic activity in various hematologic cancer cells and more profound tumor growth inhibition in multiple hematologic tumor models than venetoclax. Notably, sonrotoclax effectively inhibits venetoclax-resistant BCL2 variants, such as G101V. The crystal structures of wild-type BCL2/BCL2 G101V in complex with sonrotoclax revealed that sonrotoclax adopts a novel binding mode within the P2 pocket of BCL2 and could explain why sonrotoclax maintains stronger potency than venetoclax against the G101V mutant. In summary, sonrotoclax emerges as a potential second-generation BCL2 inhibitor for the treatment of hematologic malignancies with the potential to overcome BCL2 mutation-induced venetoclax resistance. Sonrotoclax is currently under investigation in multiple clinical trials.


Assuntos
Antineoplásicos , Compostos Bicíclicos Heterocíclicos com Pontes , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hematológicas , Proteínas Proto-Oncogênicas c-bcl-2 , Sulfonamidas , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sulfonamidas/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Animais , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Mutação , Apoptose/efeitos dos fármacos
6.
Wideochir Inne Tech Maloinwazyjne ; 18(3): 516-523, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37868278

RESUMO

Introduction: Extensive subcutaneous emphysema may lead to a significantly prolonged hospital stay, cosmetic problems, and even death without timely treatment. However, the risk factors for it have been poorly studied. Aim: To clarify the prevalence and risk factors of extensive subcutaneous emphysema after pulmonary resection by video-assisted thoracoscopic surgery. Material and methods: This is a retrospective matched case-control study. A sample of 86 cases and 258 matched controls was recruited from among 4339 patients admitted to the thoracic surgery department from October 2018 to October 2020 in a tertiary teaching hospital in China. Cases were patients who were diagnosed with extensive subcutaneous emphysema after pulmonary resection through video-assisted thoracoscopic surgery. Controls were matched in a ratio of 3 : 1 to the cases based on age and sex. Results: In this study, the incidence rate of extensive subcutaneous emphysema was 2.05%, and approximately 75.58% of the cases occurred within 1 to 4 days postoperatively. In univariate analysis, patients with extensive subcutaneous emphysema were also likely to have a significant lower body mass index, worse pulmonary function, greater intraoperative blood loss, longer time of operation, history of lung surgery, wider scope of surgery, and more extensive pleural adhesion. The results of multivariate logistic regression showed that segmentectomy (OR = 3.130, 95% CI: 1.055-9.283, p = 0.040), lobectomy (OR = 4.487, 95% CI: 1.704-11.812, p = 0.002), and extensive pleural adhesion (OR = 4.514, 95% CI: 1.763-11.556, p = 0.002) were independent risk factors. Conclusions: Segmentectomy, lobectomy, and extensive pleural adhesions were identified as independent risk factors for extensive subcutaneous emphysema after video-assisted thoracoscopic surgery.

7.
Front Immunol ; 14: 1209056, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497234

RESUMO

The characteristics of the tumour cells, as well as how tumour cells interact with their surroundings, affect the prognosis of cancer patients. The resident cells in the tumour microenvironment are mast cells (MCs), which are known for their functions in allergic responses, but their functions in the cancer milieu have been hotly contested. Several studies have revealed a link between MCs and the development of tumours. Mast cell proliferation in colorectal cancer (CRC) is correlated with angiogenesis, the number of lymph nodes to which the malignancy has spread, and patient prognosis. By releasing angiogenic factors (VEGF-A, CXCL 8, MMP-9, etc.) and lymphangiogenic factors (VEGF-C, VEGF-D, etc.) stored in granules, mast cells play a significant role in the development of CRC. On the other hand, MCs can actively encourage tumour development via pathways including the c-kit/SCF-dependent signaling cascade and histamine production. The impact of MC-derived mediators on tumour growth, the prognostic importance of MCs in patients with various stages of colorectal cancer, and crosstalk between MCs and CRC cells in the tumour microenvironment are discussed in this article. We acknowledge the need for a deeper comprehension of the function of MCs in CRC and the possibility that targeting MCs might be a useful therapeutic approach in the future.


Assuntos
Neoplasias Colorretais , Linfangiogênese , Humanos , Mastócitos/metabolismo , Prognóstico , Transdução de Sinais , Neoplasias Colorretais/patologia , Microambiente Tumoral
8.
J Psychosom Res ; 172: 111374, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37302380

RESUMO

OBJECTIVES: This study aimed to investigate preoperative anxiety in patients with lung cancer scheduled for video-assisted thoracoscopic surgery (VATS) and explore the influence of demographic factors, information needs, illness perception, and patient trust in preoperative anxiety. METHODS: This cross-sectional study was conducted at a tertiary referral center in China from August 14 to December 1, 2022. Patients with lung cancer (N = 308) scheduled for VATS were evaluated using the Amsterdam Anxiety and Information Scale (APAIS), Brief Illness Perception Questionnaire (BIPQ), and Wake Forest Physician Trust Scale (WFPTS). Multivariate linear regression was employed to determine the independent predictors of preoperative anxiety. RESULTS: The average total APAIS anxiety score was (10.6 ± 4.2). Of the sample, 48.4% reported high preoperative anxiety (APAIS-A: ≥10). Multivariate linear regression analysis showed that preoperative anxiety was higher in women (B = 0.860); and that preoperative length of stay ≥24 h (B = 0.016), more information needs (B = 0.988), more severe illness perceptions (B = 0.101) and more patient trust (B = -0.078) may lead to higher preoperative anxiety levels. CONCLUSIONS: Preoperative anxiety is common in patients with lung cancer scheduled for VATS. Therefore, more attention should be paid to women and patients with a preoperative length of stay of ≥24 h. Meeting information needs, transforming positive disease perceptions, and strengthening the doctor-patient trusting relationship are key protective factors for preoperative anxiety.


Assuntos
Neoplasias Pulmonares , Cirurgia Torácica Vídeoassistida , Humanos , Feminino , Confiança , Estudos Transversais , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Ansiedade , Percepção
10.
Anal Chem ; 95(19): 7788-7795, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37130082

RESUMO

Pollutant exposure causes a series of DNA damage in cells, resulting in the initiation and progression of diseases and even cancers. An investigation of the DNA damage induced by pollutants in living cells is significant to evaluate the cytotoxicity, genotoxicity, and carcinogenicity of environmental exposure, providing critical insight in the exploration of the etiologies of diseases. In this study, we develop a repair enzyme fluorescent probe to reveal the DNA damage caused by an environmental pollutant in living cells by single-cell fluorescent imaging of the most common base damage repair enzyme named human apurinic/apyrimidinic endonuclease 1 (APE1). The repair enzyme fluorescent probe is fabricated by conjugation of an APE1 high affinity DNA substrate on a ZnO2 nanoparticle surface to form a ZnO2@DNA nanoprobe. The ZnO2 nanoparticle serves as both a probe carrier and a cofactor supplier, releasing Zn2+ to activate APE1 generated by pollutant exposure. The AP-site in the DNA substrate of the fluorescent probe is cleaved by the activated APE1, releasing fluorophore and generating fluorescent signals to indicate the position and degree of APE1-related DNA base damage in living cells. Subsequently, the developed ZnO2@DNA fluorescent probe is applied to investigate the APE1-related DNA base damage induced by benzo[a]pyrene (BaP) in living human hepatocytes. Significant DNA base damage by BaP exposure is revealed, with a positive correlation of the damage degree with exposure time in 2-24 h and the concentration in 5-150 µM, respectively. The experimental results demonstrate that BaP has a significant effect on the AP-site damage, and the degree of DNA base damage is time-dependent and concentration-dependent.


Assuntos
Reparo do DNA , Óxido de Zinco , Humanos , Corantes Fluorescentes , Benzo(a)pireno/toxicidade , Dano ao DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , DNA
11.
Insights Imaging ; 14(1): 74, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37121955

RESUMO

OBJECTIVES: To evaluate the performance of a dual-energy computed tomography (DECT) virtual non-calcium (VNCa) technique in the detection of edema-like marrow signal intensity (ELMSI) in patients with knee joint osteoarthritis (OA) compared to magnetic resonance imaging (MRI). METHODS: The study received local ethics board approval, and written informed consent was obtained. DECT and MRI were used to examine 28 knees in 24 patients with OA. VNCa images were generated by dual-energy subtraction of calcium. The knee joint was divided into 15 regions for ELMSI grading, performed independently by two musculoskeletal radiologists, with MRI as the reference standard. We also analyzed CT numbers through receiver operating characteristics and calculated cut-off values. RESULTS: For the qualitative analysis, we obtained CT sensitivity (Readers 1, 2 = 83.7%, 89.8%), specificity (Readers 1, 2 = 99.5%, 99.5%), positive predictive value (Readers 1, 2 = 95.3%, 95.7%), and negative predictive value (Readers 1, 2 = 97.9%, 98.7%) for ELMSI. The interobserver agreement was excellent (κ = 0.92). The area under the curve for Reader 1 and Reader 2 was 0.961 (95% CI 0.93, 0.99) and 0.992 (95% CI 0.98, 1.00), respectively. CT numbers obtained from the VNCa images were significantly different between regions with and without ELMSI (p < .001). CONCLUSIONS: VNCa images have good diagnostic performance for the qualitative and quantitative analysis of knee osteoarthritis-related ELMSI.

12.
J Thorac Dis ; 15(2): 701-710, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36910101

RESUMO

Background: In 2020, there were 2,206,771 new cases of lung cancer worldwide, ranking first in mortality rate postoperative delirium (POD) is a common surgical complication and typically occurs 1-3 days after surgery which leads to prolonged hospital stay. The currently available research on POD in elderly patients was mainly carried out in cardiac surgery, orthopedic, and gastroenterology departments. It is necessary to study the incidence and risk factors of delirium in intensive care unit (ICU) elderly patients after lung cancer surgery. Methods: This study is a single-center and singe-arm observational study which examined the incidence of and factors affecting POD in elderly patients with lung cancer in ICU at our center from September 2019 to May 2020. 22 relevant variables including arterial oxygen partial pressure, postoperative sedative drug use, and other data were collected. The Confusion Assessment Method of Intensive Care Unit was used to assess the occurrence of POD, the Chinese version of the Richards-Campbell Sleep Questionnaire was used to assess patients' postoperative sleep quality, and the Mini-Mental State Examination was used to assess patients' preoperative cognitive level. Univariate and multivariate logistic regression analyses were conducted to identify the factors affecting POD in elderly ICU patients with lung cancer. Results: Among the 208 elderly ICU patients who underwent surgery for lung cancer, 32 (15.38%) had POD. The results showed that postoperative blood oxygen level, preoperative cognitive level score and postoperative sleep quality score in delirium group were significantly lower than those in non-delirium group (P values were 0.002, 0.000, 0.000, respectively). The proportion of previous coronary heart disease and postoperative sedation use in delirium group was significantly higher than that in non-delirium group (P=0.008 and 0.008, respectively). Conclusions: It was observed that the preoperative Mini-Mental State Examination (MMSE) score and postoperative Richards-Campbell Sleep Questionnaire (RCSQ) score of the delirium group were significantly lower than those of the non-delirium group, and this trend was still observed after adjusting for influencing factors. It is suggested that the difference of cognitive level in elderly lung cancer population has a significant effect on the occurrence of POD. In clinical work, we should pay more attention to patients with preoperative cognitive impairment, hypoxic state, and postoperative sleep disturbance.

13.
J Affect Disord ; 332: 136-142, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36990286

RESUMO

BACKGROUND: Gaining insight into abnormal functional brain network homogeneity (NH) has the potential to aid efforts to target or otherwise study major depressive disorder (MDD). The NH of the dorsal attention network (DAN) in first-episode treatment-naive MDD patients, however, has yet to be studied. As such, the present study was developed to explore the NH of the DAN in order to determine the ability of this parameter to differentiate between MDD patients and healthy control (HC) individuals. METHODS: This study included 73 patients with first-episode treatment-naive MDD and 73 age-, gender-, and educational level-matched healthy controls. All participants completed the attentional network test (ANT), Hamilton Rating Scale for Depression (HRSD), and resting-state functional magnetic resonance imaging (rs-fMRI) analyses. A group independent component analysis (ICA) was used to identify the DAN and to compute the NH of the DAN in patients with MDD. Spearman's rank correlation analyses were used to explore relationships between significant NH abnormalities in MDD patients, clinical parameters, and executive control reaction time. RESULTS: Relative to HCs, patients exhibited reduced NH in the left supramarginal gyrus (SMG). Support vector machine (SVM) analyses and receiver operating characteristic curves indicated that the NH of the left SMG could be used to differentiate between HCs and MDD patients with respective accuracy, specificity, sensitivity, and AUC values of 92.47 %, 91.78 %, 93.15 %, and 65.39 %. A significant positive correlation was observed between the left SMG NH values and HRSD scores among MDD patients. CONCLUSIONS: These results suggest that NH changes in the DAN may offer value as a neuroimaging biomarker capable of differentiating between MDD patients and healthy individuals.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Neuroimagem , Biomarcadores
16.
Comput Intell Neurosci ; 2022: 2183562, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531925

RESUMO

Background: Epilepsy is a group of chronic neurological disorders characterized by recurrent and abrupt seizures. The accurate prediction of seizures can reduce the burdens of this disorder. Now, existing studies use brain network features to classify patients' preictal or interictal states, enabling seizure prediction. However, most predicting methods are based on deep learning techniques, which have weak interpretability and high computational complexity. To address these issues, in this study, we proposed a novel two-stage statistical method that is interpretable and easy to compute. Methods: We used two datasets to evaluate the performance of the proposed method, including the well-known public dataset CHB-MIT. In the first stage, we estimated the dynamic brain functional connectivity network for each epoch. Then, in the second stage, we used the derived network predictor for seizure prediction. Results: We illustrated the results of our method in seizure prediction in two datasets separately. For the FH-PKU dataset, our approach achieved an AUC value of 0.963, a prediction sensitivity of 93.1%, and a false discovery rate of 7.7%. For the CHB-MIT dataset, our approach achieved an AUC value of 0.940, a prediction sensitivity of 93.0%, and a false discovery rate of 11.1%, outperforming existing state-of-the-art methods. Significance. This study proposed an explainable statistical method, which can estimate the brain network using the scalp EEG method and use the net-work predictor to predict epileptic seizures. Availability and Implementation. R Source code is available at https://github.com/HaoChen1994/Seizure-Prediction.


Assuntos
Epilepsia , Convulsões , Humanos , Convulsões/diagnóstico , Eletroencefalografia/métodos , Encéfalo , Couro Cabeludo , Algoritmos
17.
Poult Sci ; 101(11): 102109, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36067577

RESUMO

Though genome sequencing of Eimeria tenella predicts more than 8,000 genes, the molecular functions of many proteins remain unknown. In this study, the coding region corresponding to the mature peptide of a hypothetical protein of E. tenella (ETH_00023950) was amplified and expressed in a bacterial system. Following preparation of polyclonal antibody that recognizes ETH_00023950, the expression of ETH_00023950 in merozoites was examined. Meanwhile, we determined the transcriptomic responses of the leghorn male hepatoma (LMH) cells to its expression. Sequencing analysis showed that one single nucleotide polymorphism and one indel of ETH_00023950 of E. tenella SD-01 strain were found compared with that of the UK reference Houghton strain, leading to a frame shift and a premature stop codon. The expression of ETH_00023950 in E. tenella merozoites was confirmed by indirect immunofluorescence and Western blot analysis. Transcriptomic analysis showed that ETH_00023950 altered the expression of 2,680 genes (321 downregulated genes and 2,359 upregulated genes) in LMH cells. The RNA-sequencing data were consistent with the results of the quantitative real-time polymerase chain reaction (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that differentially expressed transcripts were significantly related to 8 pathways, including oxidative phosphorylation and TGF-beta signaling pathway. These findings contribute to understanding host-pathogen interaction and secondary bacterial infections related to E. tenella.


Assuntos
Coccidiose , Eimeria tenella , Animais , Masculino , Eimeria tenella/genética , Galinhas/genética , Transcriptoma , Merozoítos/genética , Perfilação da Expressão Gênica/veterinária , Coccidiose/veterinária , Coccidiose/metabolismo
18.
Front Vet Sci ; 9: 956040, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016802

RESUMO

Though a number of Eimeria tenella rhoptry kinase family proteins have been identified, little is known about their molecular functions. In the present study, the gene fragment encoding the matured peptide of E. tenella rhoptry kinase family protein 17 (EtROP17) was used to construct a recombinant vector, followed by transfection into leghorn male hepatoma (LMH) cells. Then, the transcriptional changes in the transfected cells were determined by RNA-seq. The expression of EtROP17 in LMH cells was validated by both Western blot and indirect immunofluorescence analysis. Our analysis showed that EtROP17 altered the expression of 309 genes (114 downregulated genes and 195 upregulated genes) in LMH cells. The quantitative real-time polymerase chain reaction (qRT-PCR) results of the selected differentially expressed genes (DEGs) were consistent with the RNA-seq data. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in nine pathways, such as toll-like receptor signaling pathway, ECM-receptor interaction, intestinal immune network for IgA production and focal adhesion. These findings reveal several potential roles of EtROP17, which contribute to understanding the molecular mechanisms underlying the host-parasite interplay.

19.
Front Psychol ; 13: 872468, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35983212

RESUMO

Neuromarketing has become a new and important topic in the field of marketing in recent years. Consumer behavior research has received increasing attention. In the past decade, the importance of marketing has also been recognized in many fields such as consumer behavior, advertising, information systems, and e-commerce. Neuromarketing uses neurological methods to determine the driving forces behind consumers' choices. Various neuroscience tools, such as eye movements, have been adopted to help reveal how consumers react to particular advertisements or objects. This information can be used as the basis for new advertising campaigns and brand promotions. To effectively explore the research trends in this field, we must understand the current situation of neuromarketing. A systematic bibliometric analysis can solve this problem by providing publishing trends and information on various topics. In this study, journals that focused on neuromarketing in the field of marketing between 2010 and 2021 were analyzed. These journals were core journals rated by the Association of Business Schools with three or more stars. According to the data analysis results, neuromarketing has 15 main journals with relevant papers. Based on the data collected by the Web of Science (WOS), this study mainly collected 119 references and analyzed the most productive countries, universities, authors, journals, and prolific publications in the field of neuromarketing via Citespace. Through the analysis of knowledge maps, this study explored the mapping of co-citation, bibliographic coupling (BC), and co-occurrence (CC). Moreover, the strongest citation bursts were used to study popular research at different time stages and analyze the research trends of neuromarketing research methods and tools. This study provides an overview of the trends and paths in neuromarketing, which can help researchers understand global trends and future research directions.

20.
BMC Nurs ; 21(1): 149, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35698185

RESUMO

BACKGROUND: Internship is a critical period during which nursing students develop clinical skills and establish professional attitudes. Requirements for nursing interns are evolving with the development of medicine and the transformation of teaching models. The emotional intelligence (EI) of nursing students has an influence on their clinical performance. This study aimed to investigate the impact of EI on the clinical ability of nursing interns. METHODS: A cross-sectional observational study was designed to include nursing students interning in a tertiary hospital in Shanghai, China from April 1, 2019 to April 30, 2020 (N = 310). Chinese versions of the EI scale (EIS) and holistic clinical assessment tool (HCAT) were used to measure the EI and clinical ability of interns, respectively. Pearson's correlation coefficient was utilized to determine the correlation between EI and clinical ability. Multiple linear regression analysis was performed to further explore the influence of EI on clinical ability, and the structural equation model (SEM) was used for multivariate path analysis. RESULTS: The mean EI and clinical ability scores of interns were 125.17 ± 14.98 and 97.91 ± 19.55, respectively, indicating an upper-moderate level in both aspects. EI scores were correlated positively with clinical ability ones (R = 0.534, p < 0.05). Multivariate path analysis showed that "managing emotions" and "facilitating thought" of EI branches have direct effects on clinical ability. Furthermore, the type of school, family financial state and the knowledge of EI indirectly influence clinical ability through their impact on "managing emotions" and "facilitating thought". CONCLUSIONS: EI is essential to enhancing the clinical ability of nursing students. EI training should focus on facilitating thought and managing emotions. It is also necessary for educators to consider the context of nursing students and the characteristics of schools.

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