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2.
Front Surg ; 11: 1367059, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38712336

RESUMO

Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant vascular tumor. It mainly occurs in the liver, lungs, bones, and other parts of the body. Reports of epithelioid hemangioendothelioma in the parotid gland are rare in both domestic and international literature. Here, we present a case report of a parotid gland epithelioid hemangioendothelioma, including its complete clinical course and imaging findings, to improve the diagnosis and treatment of this unusual disease. Case presentation: The patient, a 75-year-old female, presented with a swelling around the right ear for 2 months and pain for 20 days. Enhanced MRI of the parotid gland revealed a well-defined, round mass with homogeneous signal intensity. The mass showed low signal intensity on T1-weighted imaging, high signal intensity on T2-weighted imaging, nodular low signal intensity within, significant high signal intensity on DWI sequence, low signal intensity on ADC sequence, and heterogeneous enhancement in the arterial phase after intravenous injection of Gd-DTPA. Nodular non-enhancing low signal intensity was observed internally, and slight clearance was seen in the venous phase. The initial diagnosis before surgery was a benign lesion, but after histopathological and immunohistochemical examination, it was confirmed as epithelioid hemangioendothelioma. Intervention: Complete tumor resection was performed. Results: The patient experienced a favorable recovery, with meticulous follow-up conducted for up to 1 year revealing no signs of recurrence or metastasis. Continued patient surveillance is ongoing to substantiate and validate the long-term efficacy of the treatment. Conclusion: Due to the extreme rarity of parotid gland epithelioid hemangioendothelioma, it often leads to a high misdiagnosis rate. The most common misdiagnosis is salivary gland lymphoma, followed by epithelioid hemangiosarcoma. When the lesion is multifocal, fusiform, with internal necrosis, and shows punctate low signal intensity on T2-weighted imaging, significant enhancement in the arterial phase, particularly with more pronounced peripheral enhancement, and persistent enhancement in the venous and delayed phases, epithelioid hemangioendothelioma should be considered. However, the current clinical diagnosis of epithelioid hemangioendothelioma still primarily relies on immunohistochemical methods.

3.
Am J Ophthalmol ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615831

RESUMO

PURPOSE: To evaluate changes in retinal microvascular density and choroidal vascularity in patients with retinoblastoma (RB) after intra-arterial chemotherapy (IAC). DESIGN: Retrospective clinical cohort study. METHODS: This study included 12 unilateral RB eyes treated with IAC (RB tumour), 12 contralateral normal eyes (RB fellow), and 12 healthy controls. The macular retinal thickness and retinal microvascular structure, including foveal avascular zone (FAZ) area, the macular and peripapillary superficial vessel density (SVD) and deep vessel density (DVD), were measured by optical coherence tomography angiography (OCTA). The choroidal thickness (ChT) and choroidal vascularity, including total choroidal area (TCA), luminal area (LA), stromal area (SA) and Choroidal Vascularity Index (CVI), were measured by spectral-domain optical coherence tomography (SD-OCT). A comparison among the three groups was conducted, while the correlations among the parameters were analyzed. RESULTS: Between the three cohorts, the foveal retinal thickness, the SVD, DVD, ChT, TCA, LA, SA and CVI were significantly lower in RB tumour compared to RB fellow and the control eyes (all P<0.01). There were no significant differences in the parameters between the contralateral and control eyes. The correlation analyses indicated a significant negative correlation between the total melphalan dose and foveal and parafoveal DVD, ChT, and LA. CONCLUSIONS: The retinal microvascular density and choroidal vascularity were lower in unilateral RB treated with IAC, and seemed to be related to the total melphalan dose. Moreover there were no measurable changes in the contralateral eyes.

4.
Vet Microbiol ; 291: 110012, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387235

RESUMO

The ubiquitin-binding enzyme E2J1 is located on the endoplasmic reticulum membrane. It plays a role in transport throughout the process of ubiquitination. In mammals, UBE2J1 can promote RNA virus replication. However, the biological function of chicken UBE2J1 is unclear. In this study, chicken UBE2J1 was cloned for the first time, and UBE2J1 overexpression and shRNA knockdown plasmids were constructed. In chicken embryo fibroblasts, overexpression of UBE2J1 promoted the replication of subtype A avian leukosis virus, while knockdown of UBE2J1 inhibited the replication of ALV-A virus. In addition, we divided virus replication into virus adsorption and invasion into DF-1 cells, synthesis of proviral DNA, and release of viral particles. UBE2J1 promoted the replication of ALV-A virus by promoting the synthesis of proviral DNA. This result was caused by UBE2J1 inhibiting the production of interferon by inhibiting the STAT3/IRF1 pathway. We mutated ser at position 184 of UBE2J1 to Gly and found that this site plays a role as the phosphorylation site of UBE2J1. We confirmed that UBE2J1 promotes ALV-A replication in chicken embryo fibroblasts by inhibiting the STAT3/IRF1 pathway. This study provides new ideas and insights into ubiquitin-related proteins and antiviral immunity.


Assuntos
Vírus da Leucose Aviária , Leucose Aviária , Animais , Embrião de Galinha , Vírus da Leucose Aviária/genética , Vírus da Leucose Aviária/metabolismo , Galinhas , Mamíferos , Provírus , Transdução de Sinais , Ubiquitinas , Fator de Transcrição STAT3/metabolismo , Fatores Reguladores de Interferon/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo
5.
Patient Educ Couns ; 123: 108206, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38422949

RESUMO

OBJECTIVE: To examine the effectiveness of health education and counseling on the stages of change, decisional balance, and smoking cessations elf-efficacy in smokers with no intention of quitting. METHODS: A prospective self-controlled design was conducted between December 2020 and December 2022. The research period was divided into a control stage (first to fourth weeks) and an experimental stage (fifth to eighth weeks). Patients with coronary artery disease (CAD) and habitually smoked were recruited. Pearson correlation and a one-factor repeated-measurement analysis were performed to assess the effectiveness of the intervention. RESULTS: In total, 108 male CAD patients with a mean age of 58.1 years were recruited. After 4 weeks of the intervention, 55 (51%) exhibited behavior change (X 2 = 18.03, p = .001). The decisional balance and smoking cessation self-efficacy scores significantly improved in the experimental stage. No significant differences were observed in the control stage. CONCLUSIONS: Four weeks of health education and counseling could effectively improve participants' stage of change, decisional balance, and smoking cessation self-efficacy. PRACTICE IMPLICATION: Healthcare professionals can play key roles in helping CAD patients successfully quit smoking through individual education and counseling.


Assuntos
Abandono do Hábito de Fumar , Humanos , Masculino , Pessoa de Meia-Idade , Abandono do Hábito de Fumar/psicologia , Estudos Prospectivos , Modelo Transteórico , Aconselhamento , Educação em Saúde , Atenção à Saúde
6.
Int J Gynaecol Obstet ; 164(3): 1212-1219, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37953647

RESUMO

OBJECTIVE: To estimate the rate and risk factors of re-intervention for patients with uterine fibroids (UFs) undergoing high-intensity focused ultrasound (HIFU) at different age distributions. METHOD: A retrospective cohort study was conducted in Nanchong Central Hospital, recruiting a total of 672 patients with UFs undergoing HIFU from June 2017 to December 2019. Using univariate and multivariate logistic regression, risk factors for re-intervention were assessed. RESULTS: Among 401 patients with UFs who completed the follow-up visits (median 47 months, range 34-61), 50 (12.46%) patients underwent re-intervention (such as high-intensity focused ultrasound, uterine artery embolization, myomectomy and hysterectomy). In the different age distributions, the re-intervention rate was 17.5% (34/194) in patients aged <45 years and 7.7% (16/207) in those aged ≥45 years. Regarding the younger patient group (aged <45 years), hypo- or iso-intensive fibroids in T2-weighted magnetic resonance imaging (T2WI) intensity may elevate the risk of re-intervention for UFs (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.37-6.62; P = 0.007). Among the older patient group (aged ≥45 years), preoperative anemic patients had an increased risk of re-intervention compared with those without anemia (OR 3.30, 95% CI 1.01-10.37; P = 0.041). CONCLUSION: The re-intervention rate of HIFU decreased with increasing age. Among those aged <45 years, T2WI intensity was the independent risk factor for re-intervention, and among those aged ≥45 years, preoperative anemic status may be related to re-intervention outcome.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Humanos , Neoplasias Uterinas/cirurgia , Estudos Retrospectivos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Leiomioma/cirurgia , Miomectomia Uterina/efeitos adversos , Resultado do Tratamento , Imageamento por Ressonância Magnética/métodos
7.
World J Clin Cases ; 11(28): 6949-6954, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37901030

RESUMO

BACKGROUND: Malignant proliferating trichilemmal tumor (MPTT) is an infrequent malignant neoplasm originating from cutaneous appendages, with only a handful of documented cases. This report delineates a unique instance of MPTT situated in the neck, accompanied by lymph node metastasis. A comprehensive exposition of its clinical trajectory and imaging manifestation is presented, aiming to enhance comprehension and management of this atypical ailment. CASE SUMMARY: Patient concerns: A 79-year-old male presented with a longstanding right neck mass persisting for over six decades, exhibiting recent enlargement over the past year. Diagnoses: Enhanced magnetic resonance imaging of the neck unveiled an elliptical mass on the right neck side, characterized by an ill-defined border and a heterogeneous signal pattern. The mass exhibited subdued signal intensity on T1-weighted imaging (T1WI) and a heterogeneous high signal on T2-weighted imaging (T2WI), interspersed with a lengthy T1 and T2 cystic signal motif. Close anatomical association with the submandibular gland joint was noted, and intravenous gadolinium diethylene triamine pentaacetic acid administration facilitated conspicuous enhancement. Substantial enhancement of the solid segment prompted an initial preoperative diagnosis of malignant nerve sheath tumor. However, post-surgery histopathological and immunohistochemical analysis conclusively confirmed the diagnosis as malignant hyperplastic external hair root sheath tumor. Intervention: Complete excision of the tumor was successfully executed. Outcomes: The patient experienced a favorable postoperative recovery. CONCLUSION: Malignant proliferative trichilemmal tumor external hair root sheath tumor is a cystic-solid lesion, appearing as low signal on T1WI images or high signal on T2WI with enhancement of the solid component. Suspicions of malignancy are heightened when the tumor border is indistinct, tissue planes are breached, or when linear or patchy high signals are observed in the subcutaneous tissue on T1 liver acquisition with volume acceleration enhanced images along with intermediate signal on T2WI and restricted diffusion on diffusion-weighted imaging images. Strong consideration for malignancy should arise if there are signs of compromised adjacent tissue relationships or direct invasion evident on imaging. We have incorporated the above-mentioned content into the entire manuscript.

8.
J Bioinform Comput Biol ; 21(5): 2350022, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37899354

RESUMO

The polyproline-II (PPII) structure domain is crucial in organisms' signal transduction, transcription, cell metabolism, and immune response. It is also a critical structural domain for specific vital disease-associated proteins. Recognizing PPII is essential for understanding protein structure and function. To accurately predict PPII in proteins, we propose a novel method, AAindex-PPII, which only adopts amino acid index to characterize protein sequences and uses a Bidirectional Gated Recurrent Unit (BiGRU)-Improved TextCNN composite deep learning model to predict PPII in proteins. Experimental results show that, when tested on the same datasets, our method outperforms the state-of-the-art BERT-PPII method, achieving an AUC value of 0.845 on the strict data and an AUC value of 0.813 on the non-strict data, which is 0.024 and 0.03 higher than that of the BERT-PPII method. This study demonstrates that our proposed method is simple and efficient for PPII prediction without using pre-trained large models or complex features such as position-specific scoring matrices.


Assuntos
Aminoácidos , Peptídeos , Peptídeos/química , Proteínas , Sequência de Aminoácidos
9.
Acta Pharmacol Sin ; 44(7): 1442-1454, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36658427

RESUMO

Acute kidney injury (AKI) caused by anti-tumor drugs, such as cisplatin, is a severe complication with no effective treatment currently, leading to the reduction or discontinuation of chemotherapy. Natural products or herbal medicines are gradually considered as promising agents against cisplatin-induced AKI with the advantages of multi-targeting, multi-effects, and less resistance. In this study, we investigated the effects of kaempferide, a natural flavonoid extracted from the rhizome of Kaempferia galanga, in experimental AKI models in vitro and in vivo. We first conducted pharmacokinetic study in mice and found a relative stable state of kaempferide with a small amount of conversion into kaempferol. We showed that both kaempferide (10 µM) and kaempferol (10 µM) significantly inhibited cisplatin-caused injuries in immortalized proximal tubule epithelial cell line HK-2. In AKI mice induced by injection of a single dose of cisplatin (15 mg/kg), oral administration of kaempferide (50 mg/kg) either before or after cisplatin injection markedly improved renal function, and ameliorated renal tissue damage. We demonstrated that kaempferide inhibited oxidative stress and induced autophagy in cisplatin-treated mice and HK-2 cells, thus increasing tubular cell viability and decreasing immune responses to attenuate the disease progression. In addition, treatment with kaempferide significantly ameliorated ischemia-reperfusion-induced renal injury in vitro and in vivo. We conclude that kaempferide is a promising natural product for treating various AKI. This study has great implications for promotion of its use in healthcare products, and help to break through the limited use of cisplatin in the clinic.


Assuntos
Injúria Renal Aguda , Cisplatino , Camundongos , Animais , Cisplatino/farmacologia , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Estresse Oxidativo , Autofagia , Apoptose , Camundongos Endogâmicos C57BL
10.
Front Vet Sci ; 9: 1031480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452148

RESUMO

Avian leukemia virus subgroup A (ALV-A) infection slows chicken growth, immunosuppression, and tumor occurrence, causing economic loss to the poultry industry. According to previous findings, A20 has a dual role in promoting and inhibiting tumor formation but has rarely been studied in avians. In this study, A20 overexpression and shRNA interference recombinant adenoviruses were constructed and inoculated into chicken embryos, and ALV-A (rHB2015012) was inoculated into 1-day-old chicks. Analysis of body weight, organ index, detoxification, antibody production, organ toxin load, and Pathological observation revealed that A20 overexpression could enhance ALV-A pathogenicity. This study lays the foundation for subsequent exploration of the A20-mediated tumorigenic mechanism of ALV-A.

11.
Viruses ; 14(10)2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36298765

RESUMO

Hens infected with avian leukosis virus subgroup A (ALV-A) experience stunted growth, immunosuppression, and potentially, lymphoma development. According to past research, A20 can both promote and inhibit tumor growth. In this study, DF-1 cells were infected with ALV-A rHB2015012, and Gp85 expression was measured at various time points. A recombinant plasmid encoding the chicken A20 gene and short hairpin RNA targeting chicken A20 (A20-shRNA) was constructed and transfected into DF-1 cells to determine the effect on ALV-A replication. The potential signaling pathways of A20 were explored using bioinformatics prediction, co-immunoprecipitation, and other techniques. The results demonstrate that A20 and ALV-A promoted each other after ALV-A infection of DF-1 cells, upregulated A20, inhibited TRAF6 ubiquitination, and promoted STAT3 phosphorylation. The phosphorylated-STAT3 (p-STAT3) promoted the expression of proto-oncogene c-myc, which may lead to tumorigenesis. This study will help to further understand the tumorigenic process of ALV-A and provide a reference for preventing and controlling ALV.


Assuntos
Vírus da Leucose Aviária , Leucose Aviária , Doenças das Aves Domésticas , Animais , Feminino , Vírus da Leucose Aviária/genética , Fator 6 Associado a Receptor de TNF/genética , RNA Interferente Pequeno/genética , Galinhas/genética , Ubiquitinação , Proto-Oncogenes
12.
Front Vet Sci ; 9: 970818, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246325

RESUMO

A strain of avian leukosis virus (ALV) belonging to a new envelope subgroup J (ALV-J) emerged in 1988 as a new subgroup of ALV and spread rapidly throughout the world. Due to the infection and spread of ALV-J, the global poultry industry experienced a significant loss. Although the disease had been prevented and controlled effectively by culling domestic chickens in the infected zone, a few field cases of ALV-J infection were reported in China in recent years. This study was conducted to characterize the genome and analyze the lesions and histopathology of the ALV-J strain named HB2020, which was isolated from layer chickens in Hubei Province, China. The full-length proviral genome sequence analysis of ALV-J HB2020 revealed that it was a recombinant strain of ev-1 and HPRS-103 in the gag gene in comparison to ALV-J prototype HPRS-103. In the 3'-untranslated region (3'UTR) of the nucleotide sequence, there were found 205-base pairs (bp) deletion, of which 175 were detected in the redundant transmembrane (rTM) region. Besides, the surface glycoprotein gene gp85 had five mutations in a conservative site, whereas the transmembrane protein gene gp37 was relatively conserved. The animal experiments conducted later on this strain have shown that HB2020 can cause various neoplastic lesions in chickens, including enlarged livers with hemangiomas and spleens with white nodules. Additionally, as the exposure time increased, the number of tumor cells that resembled myelocytes in the blood smears of infected chickens gradually increased. These results indicated that HB2020 on recombination with ALV subgroup E (ALV-E) and ALV-J could induce severe hemangiomas and myelocytomas. This inference might provide a molecular basis for further research about the pathogenicity of ALV and emphasize the need for control and prevention of avian leukosis.

13.
Int Orthop ; 46(10): 2299-2306, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35697865

RESUMO

INTRODUCTION: Monteggia fracture-dislocation refers to traumatic ulnar fractures and dislocation of the radial head, which is one of the most frequently missed injuries, especially in children. The most widespread attitude towards chronic Monteggia lesion is the open reduction of the radial head associated with ulnar osteotomy with or without annular ligament reconstruction. Our study aimed to analyze the risk factors for redislocation after surgical management of chronic Monteggia lesion and the benefits of annular ligament reconstruction and radiocapitellar pinning in paediatric. MATERIALS AND METHODS: We retrospectively reviewed patients treated with reconstruction surgery for chronic Monteggia fracture-dislocation in our department between 2005 and 2017, with a minimum two years' follow-up. The reconstruction surgery included ulnar osteotomy performed in all patients, annular ligament repair or reconstruction or fixation of radiocapitellar joint, or radial osteotomy in some patients. We collected the related clinical data and evaluated the risk factors of redislocation using logistic regression analyses and a two-piecewise linear regression model with a smoothing function, after reconstruction. RESULTS: Throughout a mean six years' follow-up (range, 2-14 years), 62 patients (42 males, 20 females; average age 6.49 years range, 2-13 years) were reviewed. Of the radiocapitellar joints, 16.1% was noted to have redislocation. Univariate risk analysis showed age, time from injury to surgery, and radial osteotomy were risk factors for a recurrent radiocapitellar redislocation. Time from injury to surgery was found to be independent predictor of redislocation in multivariate analysis. However, there were significant nonlinear associations between time from injury to surgery and redislocation in multivariate logistic regression analysis after multivariate adjustment (p for nonlinear = 0.023). Every one month increase was associated with a 1.37-fold increase in redislocation, in participants within one year after injury. CONCLUSION: In conclusion, the surgery of chronic Monteggia fracture-dislocation should be done as quickly as possible within one year after injury. Associated annular ligament reconstruction or fixation of radiocapitellar joint does not seem to be helpful.


Assuntos
Lesões no Cotovelo , Fratura de Monteggia , Criança , Feminino , Humanos , Masculino , Fratura de Monteggia/cirurgia , Estudos Retrospectivos , Fatores de Risco , Ulna/cirurgia
14.
Appl Microbiol Biotechnol ; 106(2): 729-742, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34971411

RESUMO

Avian leukosis, caused by avian leukosis virus (ALV), is an infectious tumor disease and severely hinders the development of the poultry industry. The use of Lactobacillus plantarum (L. plantarum) could effectively alleviate viremia in the early period of J subgroup ALV (ALV-J) infection. In this study, an invasive L. plantarum NC8 expressing Gp85 protein of ALV-J was constructed. After chickens were orally administered the recombinant invasive NC8, the levels of expression of CD4+ and CD8+ T lymphocytes in peripheral blood and spleen by flow cytometry and the proliferation ability of splenocytes by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were examined, and the contents of cytokines, the anti-ALV-J antibody in serum, and mucosal antibody sIgA in intestinal lavage fluid were detected by enzyme-linked immunosorbent assay (ELISA). The immunoprotective efficiency was evaluated by monitoring the infection rate, the percent of cloacal swabs and survival, body weight gain, the organ indexes, and relative virus loads after challenge with ALV-J. The results showed that the recombinant invasive strain (FnBPA-gp85) could promote the expression levels of the CD8+T cells in peripheral blood and spleen, the proliferation of splenocytes, the secretions of cytokines interleukin 2 (IL-2) and γ-interferon (IFN-γ), and the production of IgG and sIgA compared with the PBS and FnBPA control groups in chickens. The FnBPA-gp85 group was exhibited the highest immune protection against ALV-J infection. The above results indicated that the recombinant invasive NC8 could promote the cellular immunity, humoral immunity, and mucosal immunity responses in chicken and provide a new method for exploring the live vaccine against ALV-J.Key points• The FnBPA-gp85 strain could enhance cellular immunity response.• The FnBPA-gp85 strain could improve the immune protection against ALV-J infection.


Assuntos
Vírus da Leucose Aviária , Leucose Aviária , Lactobacillus plantarum , Doenças das Aves Domésticas , Animais , Anticorpos Antivirais , Leucose Aviária/prevenção & controle , Vírus da Leucose Aviária/genética , Galinhas , Doenças das Aves Domésticas/prevenção & controle , Proteínas do Envelope Viral/genética
15.
J Environ Pathol Toxicol Oncol ; 40(4): 61-72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34936301

RESUMO

The aim of this study was to identify the roles of neuregulin 1 (NRG1) during the tumor progression in non-small-cell lung cancer (NSCLC). NSCLC patients with lung squamous cell carcinoma and lung adenocarci-noma were enrolled in this study. The expression of NRG1, vascular endothelial growth factor (VEGF) and surviving in clinical specimens was examined using immunohistochemistry analysis. The cytokine production in plasma was evaluated by ELISA. The levels of NRG1-associated molecules were determined using western blotting. The proliferation and apoptosis of cells with NRG1 knockdown were accessed by CCK-8 assay and flow cytometry. Upregulation of NRG1 as well as tumor-associated angiogenesis markers VEGF and survivin was detected in tissue and serum samples of NSCLC patients compared with the control. Furthermore, positive correlation with NSCLC levels and VEGF/survivin was also found in NSCLC specimens. In addition, upregulation of NRG1, VEGF and survivin was associated with poor overall survival in NSCLC patients. Moreover, enhanced production of NRG1 was detected in serum samples from NSCLC patients compared with healthy donors, and ROC analysis revealed the importance of NRG1 levels on distinguishing NSCLC samples and the controls. These findings suggested the novel diagnostic value of NRG1 in NSCLC. Additionally, upregulated protein levels of NRG1 and its target genes were also found in tissues samples of NSCLC patients compared with normal controls. These data indicated that NRG1 was a promising marker NSCLC, and it could be involved in tumor progression by targeting its downstream target including ErbB-Akt axis. Furthermore, the growth of lung cancer cells was suppressed by the knockdown of NRG1. Our findings could provide guidance for more accurate diagnosis for NSCLC, and future therapeutic approaches might be developed by better understanding of NRG-1-modulated molecular mechanisms during the tumor development in NSCLC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Neuregulina-1/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuregulina-1/metabolismo
16.
J Med Chem ; 64(15): 11288-11301, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34337952

RESUMO

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays an important role in one-carbon metabolism. The MTHFD2 gene is upregulated in various cancers but very low or undetectable in normal proliferating cells, and therefore a potential target for cancer treatment. In this study, we present the structure of MTHFD2 in complex with xanthine derivative 15, which allosterically binds to MTHFD2 and coexists with the substrate analogue. A kinetic study demonstrated the uncompetitive inhibition of MTHFD2 by 15. Allosteric inhibitors often provide good selectivity and, indeed, xanthine derivatives are highly selective for MTHFD2. Moreover, several conformational changes were observed upon the binding of 15, which impeded the binding of the cofactor and phosphate to MTHFD2. To the best of our knowledge, this is the first study to identify allosteric inhibitors targeting the MTHFD family and our results would provide insights on the inhibition mechanism of MTHFD proteins and the development of novel inhibitors.


Assuntos
Aminoidrolases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Metilenotetra-Hidrofolato Desidrogenase (NADP)/antagonistas & inibidores , Enzimas Multifuncionais/antagonistas & inibidores , Xantina/farmacologia , Sítio Alostérico/efeitos dos fármacos , Aminoidrolases/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Modelos Moleculares , Estrutura Molecular , Enzimas Multifuncionais/metabolismo , Relação Estrutura-Atividade , Xantina/síntese química , Xantina/química
17.
Poult Sci ; 100(7): 101108, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34116348

RESUMO

Avian leukosis virus subgroup J (ALV-J) is an avian oncogenic retrovirus that has caused huge economic losses in the poultry industry due to its great pathogenicity and transmission ability. However, the continuous emergence of new strains would bring challenges to diagnosis and control of ALV-J. .This study focuses on preparing the monoclonal antibody (MAb) against ALV-J Gp85 and identifying its epitope. The truncated ALV-J gp85 gene fragment was amplified and then cloned into expression vectors. Purified GST-Gp85 was used to immune mice and His-Gp85 was used to screen MAb. Finally, a hybridoma cell line named J16 that produced specific MAb against the ALV-J. Immunofluorescence assay showed that MAb J16 specifically recognized ALV-J rather than ALV-A or ALV-K infected DF-1 cells. To identify the epitope recognized by MAb J16, fourteen partially overlapping ALV-J Gp85 fragments were prepared and tested by Western blot. The results indicated that peptide 150-LIRPYVNQ-157 was the minimal epitope of ALV-J Gp85 recognized by MAb J16. Alignment analysis of Gp85 from different ALV subgroups showed that the epitope keep high conservation among 36 ALV-J strains, but significant different from that of ALV subgroup A, B, C, D, E and K. Overall, we prepared a MAb specific against ALV-J and identified peptide 150-LIRPYVNQ-157 as a novel specific epitope of ALV-J Gp85, which may assist in laying the foundation for specific ALV-J detection methods.


Assuntos
Vírus da Leucose Aviária , Leucose Aviária , Doenças das Aves Domésticas , Doenças dos Roedores , Animais , Anticorpos Monoclonais , Galinhas , Epitopos , Camundongos , Proteínas do Envelope Viral
18.
ACS Appl Mater Interfaces ; 13(15): 17707-17716, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33847109

RESUMO

Nickel-rich Li(NixCoyMn1-x-yO2) (x ≥ 0.6) is considered to be a predominant cathode for next-generation lithium-ion batteries (LIBs) due to its towering specific energy density. Unfortunately, serious structural degradation causes rapid capacity degradation with the increase in nickel content. Herein, a Co and Ti co-modified LiNi0.8Co0.1Mn0.1O2 (NCM-811) cathode ameliorates the reversible capacity together with the rate capability by obviously alleviating the lattice structure degradation and microscopic intergranular cracks. Further studies show that the titanium doping effectively reduces the cation mixing and also stabilizes the crystal structure, while the spinel phase formed at the surface by a cobalt oxide coating is much stable than the layered phase at high voltage, which can alleviate the generation of micro-cracks. After 0.5% Co oxide coating and 1% Ti doping (T1Co0.5-NCM), a superior rate capability (121.75 mA h g-1 at 20 C between 2.7 and 4.5 V) and predominant capacity retention (74.2%) are observed compared with the pristine NCM-811 (59.5%) after 400 cycles between 2.7 and 4.7 V. This work supplies an eminent design of high-voltage and high-rate layered cathode materials and has a huge application prospect in the next generation of high-energy LIBs.

19.
Acta Pharmacol Sin ; 42(12): 1951-1969, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33750909

RESUMO

Cisplatin is a clinically advanced and highly effective anticancer drug used in the treatment of a wide variety of malignancies, such as head and neck, lung, testis, ovary, breast cancer, etc. However, it has only a limited use in clinical practice due to its severe adverse effects, particularly nephrotoxicity; 20%-35% of patients develop acute kidney injury (AKI) after cisplatin administration. The nephrotoxic effect of cisplatin is cumulative and dose dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI result in impaired renal tubular function and acute renal failure, chronic kidney disease, uremia, and hypertensive nephropathy. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, apoptosis, oxidative stress, inflammation, and vascular injury in the kidneys. At present, there are no effective drugs or methods for cisplatin-induced kidney injury. Recent in vitro and in vivo studies show that numerous natural products (flavonoids, saponins, alkaloids, polysaccharide, phenylpropanoids, etc.) have specific antioxidant, anti-inflammatory, and anti-apoptotic properties that regulate the pathways associated with cisplatin-induced kidney damage. In this review we describe the molecular mechanisms of cisplatin-induced nephrotoxicity and summarize recent findings in the field of natural products that undermine these mechanisms to protect against cisplatin-induced kidney damage and provide potential strategies for AKI treatment.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Antineoplásicos/toxicidade , Produtos Biológicos/uso terapêutico , Cisplatino/toxicidade , Substâncias Protetoras/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologia , Animais , Apoptose/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
20.
Mol Med Rep ; 23(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760129

RESUMO

Inflammation, which causes injury to vascular endothelial cells, is one of the major factors associated with atherosclerosis (AS); therefore, inhibition of endothelial inflammation is a key step toward preventing AS. The present study aimed to investigate the effects of bakkenolide­IIIa (Bak­IIIa), an important active component of bakkenolides, on endothelial inflammation, as well as the mechanisms underlying such effects. Lipopolysaccharide (LPS)­damaged human umbilical vein endothelial cells (HUVECs) were treated with Bak­IIIa. The results of the MTT assay and enzyme­linked immunosorbent assay indicated that Bak­IIIa significantly alleviated survival inhibition, and decreased the levels of LPS­induced TNF­α, interleukin (IL)­1ß, IL­8, and IL­6. Furthermore, long noncoding RNA (lncRNA) microarray analyses revealed 70 differentially expressed lncRNAs (DELs) in LPS­damaged HUVECs treated with Bak­IIIa. lncRNA target prediction results revealed that 44 DELs had 52 cis­targets, whereas 12 DELs covered 386 trans­targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses of the trans­targets indicated that three GO terms were associated with inflammation. Therefore, 17 targets involved in these GO terms and six relevant DELs were screened out. Validation via reverse transcription­quantitative PCR indicated that the fold change of NR_015451 (LINC00294) was the highest among the six candidates and that overexpression of LINC00294 significantly alleviated LPS­induced survival inhibition and inflammatory damage in HUVECs. In conclusion, Bak­IIIa ameliorated LPS­induced inflammatory damage in HUVECs by upregulating LINC00294. Thus, Bak­IIIa exhibited potential for preventing vascular inflammation.


Assuntos
Inflamação/tratamento farmacológico , RNA Longo não Codificante/genética , Sesquiterpenos/farmacologia , Fator de Necrose Tumoral alfa/genética , Apoptose/efeitos dos fármacos , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-6/genética , Interleucina-8/genética , Lipopolissacarídeos/toxicidade
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