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1.
BMC Genomics ; 22(1): 653, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34511071

RESUMO

BACKGROUND: As non-coding RNA molecules of more than 200 bp in length, long non-coding RNAs (lncRNAs) play a variety of roles in biological processes, including regulating the immune responses to bacterial infections. In recent years, there have been many in-depth studies on mammalian lncRNAs, but the relevant studies in fish are very limited. Meanwhile, since lncRNAs are not conserved among species, it is difficult to apply the existing results directly to unstudied species. RESULTS: To obtain the information of lncRNAs in Megalobrama amblycephala, one of the most economically important freshwater fish in China, also to better understand the biological significance of lncRNAs in the immunity system, the fish liver at 0, 4, 12, 24, and 72 h post Aeromonas hydrophila infection (hpi) were obtained for lncRNA-sequencing (lncRNA-seq). A total of 14,849 lncRNAs were identified, and 2196 lncRNAs showed significant differences at different time points post A. hydrophila infection. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the target genes of the differentially expressed lncRNAs were enriched in several pathways related to immune such as apoptosis, inflammation, and immune response. Time-specific modules were then identified, using weighted correlation network analysis (WGCNA), and 28 modules significantly correlated with different time point after infection were found. Furthermore, four immune-related genes and six lncRNAs in the time-specific modules were subsequently verified by RT-qPCR. CONCLUSIONS: The above findings reveal the discovery of widespread differentially expressed lncRNAs in the M. amblycephala liver post A. hydrophila infection, suggesting that lncRNAs might participate in the regulation of host response to bacterial infection, enriching the information of lncRNAs in teleost and providing a resources basis for further studies on the immune function of lncRNAs.


Assuntos
Cyprinidae , RNA Longo não Codificante , Aeromonas hydrophila , Animais , Cyprinidae/genética , Fígado , RNA Longo não Codificante/genética , RNA Mensageiro/genética
2.
Dev Comp Immunol ; 124: 104185, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34174243

RESUMO

Circular RNAs (circRNAs), a class of non-coding RNAs, play an important role in regulating various biological processes. In the present study, circRNAs from the Megalobrama amblycephala liver were identified at five different time points post Aeromonas hydrophila using RNA-seq technology. A total of 250 circRNAs were identified, of which 106 were differentially expressed (DE) in ten pairwise comparisons. GO and KEGG analyses showed that the parental genes of DE circRNAs were enriched in phagocytosis, complement and coagulation cascades, and Fc gamma R-mediated phagocytosis pathways. According to ceRNA hypothesis, the interaction network of circRNAs, miRNAs and mRNAs was constructed. Moreover, WGCNA was conducted, and five specific modules significantly related to bacterial infection were identified. All the above results reveal the important role of circRNAs in immune response, which enriches the information of circRNAs in teleost, and helps to understand the immune response mechanism of M. amblycephala to A. hydrophila.

3.
Mol Metab ; 44: 101131, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278637

RESUMO

BACKGROUND: Live kinase B1 (LKB1) is a tumor suppressor that is mutated in Peutz-Jeghers syndrome (PJS) and a variety of cancers. Lkb1 encodes serine-threonine kinase (STK) 11 that activates AMP-activated protein kinase (AMPK) and its 13 superfamily members, regulating multiple biological processes, such as cell polarity, cell cycle arrest, embryo development, apoptosis, and bioenergetics metabolism. Increasing evidence has highlighted that deficiency of LKB1 in cancer cells induces extensive metabolic alterations that promote tumorigenesis and development. LKB1 also participates in the maintenance of phenotypes and functions of normal cells through metabolic regulation. SCOPE OF REVIEW: Given the important role of LKB1 in metabolic regulation, we provide an overview of the association of metabolic alterations in glycolysis, aerobic oxidation, the pentose phosphate pathway (PPP), gluconeogenesis, glutamine, lipid, and serine induced by aberrant LKB1 signals in tumor progression, non-neoplastic diseases, and functions of immune cells. MAJOR CONCLUSIONS: In this review, we summarize layers of evidence demonstrating that disordered metabolisms in glucose, glutamine, lipid, and serine caused by LKB1 deficiency promote carcinogenesis and non-neoplastic diseases. The metabolic reprogramming resulting from the loss of LKB1 confers cancer cells with growth or survival advantages. Nevertheless, it also causes a metabolic frangibility for LKB1-deficient cancer cells. The metabolic regulation of LKB1 also plays a vital role in maintaining cellular phenotype in the progression of non-neoplastic diseases. In addition, lipid metabolic regulation of LKB1 plays an important role in controlling the function, activity, proliferation, and differentiation of several types of immune cells. We conclude that in-depth knowledge of metabolic pathways regulated by LKB1 is conducive to identifying therapeutic targets and developing drug combinations to treat cancers and metabolic diseases and achieve immunoregulation.

4.
Comput Methods Programs Biomed ; 199: 105912, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360683

RESUMO

BACKGROUND: Mechanical ventilation (MV) is a core intensive care unit (ICU) therapy. Significant inter- and intra- patient variability in lung mechanics and condition makes managing MV difficult. Accurate prediction of patient-specific response to changes in MV settings would enable optimised, personalised, and more productive care, improving outcomes and reducing cost. This study develops a generalised digital clone model, or in-silico virtual patient, to accurately predict lung mechanics in response to changes in MV. METHODS: An identifiable, nonlinear hysteresis loop model (HLM) captures patient-specific lung dynamics identified from measured ventilator data. Identification and creation of the virtual patient model is fully automated using the hysteresis loop analysis (HLA) method to identify lung elastances from clinical data. Performance is evaluated using clinical data from 18 volume-control (VC) and 14 pressure-control (PC) ventilated patients who underwent step-wise recruitment maneuvers. RESULTS: Patient-specific virtual patient models accurately predict lung response for changes in PEEP up to 12 cmH2O for both volume and pressure control cohorts. R2 values for predicting peak inspiration pressure (PIP) and additional retained lung volume, Vfrc in VC, are R2=0.86 and R2=0.90 for 106 predictions over 18 patients. For 14 PC patients and 84 predictions, predicting peak inspiratory volume (PIV) and Vfrc yield R2=0.86 and R2=0.83. Absolute PIP, PIV and Vfrc errors are relatively small. CONCLUSIONS: Overall results validate the accuracy and versatility of the virtual patient model for capturing and predicting nonlinear changes in patient-specific lung mechanics. Accurate response prediction enables mechanically and physiologically relevant virtual patients to guide personalised and optimised MV therapy.


Assuntos
Respiração Artificial , Lesão Pulmonar Induzida por Ventilação Mecânica , Simulação por Computador , Humanos , Unidades de Terapia Intensiva , Mecânica Respiratória
5.
Psychiatry Res ; 289: 113043, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33242800

RESUMO

At the beginning of the 2020 New year, novel coronavirus infection continues to affect our lives. The anxiety and stress caused by rising epidemic data, the helplessness and fear caused by city closure and isolation, and the boredom and irritability caused by extended holiday grounding all have a great impact on the psychology of students. In this special stress period of "suspension of classes and non-stop learning", teachers actively help and guide students, do a good job of students' psychological support, perform the duties of spiritual mentors, and do a good job of students' psychological care.

6.
J Renin Angiotensin Aldosterone Syst ; 21(4): 1470320320975893, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33234024

RESUMO

Amiloride is a potassium retaining diuretic and natriuretic which acts by reversibly blocking luminal epithelial sodium channels (ENaCs) in the late distal tubule and collecting duct. Amiloride is indicated in oedematous states, and for potassium conservation adjunctive to thiazide or loop diuretics for hypertension, congestive heart failure and hepatic cirrhosis with ascites. Historical studies on its use in hypertension were poorly controlled and there is insufficient data on dose-response. It is clearly highly effective in combination with thiazide diuretics where it counteracts the adverse metabolic effects of the thiazides and its use in the Medical Research Council Trial of Older Hypertensive Patients, demonstrated convincing outcome benefits on stroke and coronary events. Recently it has been shown to be as effective as spironolactone in resistant hypertension but there is a real need to establish its potential role in the much larger number of patients with mild to moderate hypertension in whom there is a paucity of information with amiloride particularly across an extended dose range.

7.
Cell Death Dis ; 11(9): 796, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968046

RESUMO

Chemotherapy remains an essential part of diverse treatment regimens against human malignancies. However, recent progressions have revealed a paradoxical role of chemotherapies to induce the cancer stem cell-like features that facilitate chemoresistance and tumor dissemination, with the underlying mechanisms underinvestigated. The zinc-finger transcription factor Snail1 is a central regulator during the epithelial-mesenchymal transition process and is closely implicated in cancer progression. Snail1 expression is strictly regulated at multiple layers, with its stability governed by post-translational ubiquitylation that is counterbalanced by the activities of diverse E3 ligases and deubiquitylases. Here we identify the deubiquitylase USP29 as a novel stabilizer of Snail1, which potently restricts its ubiquitylation in a catalytic activity-dependent manner. Bioinformatic analysis reveals a reverse correlation between USP29 expression and prognosis in lung adenocarcinoma patients. USP29 is unique among Snail1 deubiquitylases through exhibiting chemotherapy-induced upregulation. Mechanistically, oxidative stresses incurred by chemotherapy stimulate transcriptional activation of USP29. USP29 upregulation enhances the cancer stem cell-like characteristics in lung adenocarcinoma cells to promote tumorigenesis in athymic nude mice. Our findings uncover a novel mechanism by which chemotherapy induces cancer stemness and suggest USP29 as a potential therapeutic target to impede the development of chemoresistance and metastasis in lung adenocarcinoma.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Fatores de Transcrição da Família Snail/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Estresse Oxidativo , Transfecção , Proteases Específicas de Ubiquitina/genética
8.
Medicine (Baltimore) ; 99(29): e21286, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702920

RESUMO

Calcific aortic valve disease (CAVD) is highly prevalent in our aging world and has no effective pharmaceutical treatment. Intense efforts have been made but the underlying molecular mechanisms of CAVD are still unclear.This study was designed to identify the critical genes and pathways in CAVD by bioinformatics analysis. Microarray datasets of GSE12644, GSE51472, and GSE83453 were obtained from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified and functional and pathway enrichment analysis was performed. Subsequently, the protein-protein interaction network (PPI) was constructed with Search Tool for the Retrieval of Interacting Genes and was visualized with Cytoscape to identify the most significant module. Hub genes were identified by Cytoscape plugin cytoHubba.A total of 179 DEGs, including 101 upregulated genes and 78 downregulated genes, were identified. The enriched functions and pathways of the DEGs include inflammatory and immune response, chemotaxis, extracellular matrix (ECM) organization, complement and coagulation cascades, ECM receptor interaction, and focal adhesion. The most significant module in the PPI network was analyzed and genes among it were mainly enriched in chemotaxis, locomotory behavior, immune response, chemokine signaling pathway, and extracellular space. In addition, DEGs, with degrees ≥ 10 and the top 10 highest Maximal Chique Centrality (MCC) score, were identified as hub genes. CCR1, MMP9, VCAM1, and ITGAX, which were of the highest degree or MCC score, were manually reviewed.The DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the pathogenesis of CAVD and might serve as candidate therapeutic targets for CAVD.


Assuntos
Estenose da Valva Aórtica/genética , Valva Aórtica/patologia , Calcinose/genética , Genes/genética , Predisposição Genética para Doença/genética , Estenose da Valva Aórtica/etiologia , Calcinose/etiologia , Estudos de Casos e Controles , Biologia Computacional , Genes/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos
9.
Heart Surg Forum ; 23(4): E546-E548, 2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32726213

RESUMO

BACKGROUND: Pericarditis is the most common form of pericardial disease, while constrictive pericarditis is challenging in diagnosis and is easily overlooked. CASE REPORT: A 30-year-old female presented with abdominal distension and mild lower extremity edema for 3 months. The patient was initially suspected of having cirrhosis caused by Wilson Disease. Following liver biopsy and multiple investigation, thickened, calcified pericardium was detected by echocardiography and chest computed tomography. The patient was finally diagnosed with chronic constrictive pericarditis and received pericardiectomy. Intraoperatively, we found that the heart was entirely constricted by the thickened and calcified visceral pericardium, which was completely separated from the parietal pericardium. The patient received successful pericardiectomy and had relief of symptoms after surgery. CONCLUSION: Patients with constrictive pericarditis may present with symptoms similar to that of chronic liver diseases, which makes it difficult and complicated for diagnosis. This case highlights the importance of comprehensive preoperative evaluation and maintaining clinical suspicion of pericarditis in patients with features of elevated systemic venous pressure. In addition, constrictive pericarditis with complete separation between visceral and parietal pericardium has seldom been reported.


Assuntos
Pericardiectomia/métodos , Pericardite Constritiva/diagnóstico , Pericárdio/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Ecocardiografia , Eletrocardiografia , Doença Hepática Terminal/diagnóstico , Feminino , Humanos , Pericardite Constritiva/cirurgia , Pericárdio/cirurgia , Doenças Raras
10.
Psychiatry Res ; 289: 113043, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32387793

RESUMO

At the beginning of the 2020 New year, novel coronavirus infection continues to affect our lives. The anxiety and stress caused by rising epidemic data, the helplessness and fear caused by city closure and isolation, and the boredom and irritability caused by extended holiday grounding all have a great impact on the psychology of students. In this special stress period of "suspension of classes and non-stop learning", teachers actively help and guide students, do a good job of students' psychological support, perform the duties of spiritual mentors, and do a good job of students' psychological care.


Assuntos
Ansiedade , Infecções por Coronavirus/psicologia , Intervenção na Crise , Pneumonia Viral/psicologia , Angústia Psicológica , Estresse Psicológico/psicologia , Estudantes/psicologia , Adulto , Betacoronavirus , COVID-19 , Infecções por Coronavirus/epidemiologia , Emoções , Medo , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Adulto Jovem
12.
Cell Death Differ ; 27(9): 2710-2725, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32327714

RESUMO

ErbB2 overexpression identifies a subclass of breast cancer as ErbB2-positive that is frequently associated with poor prognosis. Current ErbB2-targeted therapies have profoundly improved patient outcomes, but mutations occurring in ErbB2 have been shown to confer drug resistance. Induction of ErbB2 degradation was proposed as an intriguing strategy to battle with ErbB2-positive breast cancer and reduced mutation-incurred drug resistance. Although multiple HSP90 inhibitors have been demonstrated to effectively trigger ErbB2 degradation, none succeeded in the clinical evaluations. To develop novel ErbB2-targeting strategies, we investigated the endocytic degradation and reversible ubiquitylation of ErbB2 in breast cancer. In this study, we reveal that HSP90 inhibition leads to efficient ubiquitylation and endocytic degradation of ErbB2 through the canonical endo-lysosomal route. USP2 associates with internalized ErbB2 and prevents its lysosomal sorting and degradation via exerting deubiquitylase activity. Accordingly, the USP2 inhibitor ML364 is capable of inducing ErbB2 ubiquitylation and accelerating its turnover. ML364 potentiates the pro-degradation effects of HSP90 inhibitors on ErbB2 and hence sensitizes ErbB2-positive breast cancer cells to HSP90 inhibition. The combination of USP2 and HSP90 inhibitors effectively restrains ErbB2-positive breast cancer xenograft growth in vivo. Based on these observations, we conclude that USP2 safeguards ErbB2 surface levels by antagonizing its ubiquitylation-mediated endocytic degradation, which can be exploited to design novel therapeutic strategies against ErbB2-driven malignancies as combinatorial treatment with HSP90 inhibitors.

13.
EBioMedicine ; 53: 102693, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32114385

RESUMO

BACKGROUND: Treatment of Crohn's disease (CD) remains to be a challenge due to limited insights for its pathogenesis. We aimed to determine the role of O-Linked ß-N-acetylglucosamine (O-GlcNAc) in the development of CD and evaluate therapeutic effects of O-GlcNAc inhibitors on CD. METHODS: O-GlcNAc in intestinal epithelial tissues of CD, adherent-invasive Escherichia coli (AIEC) LF82-infected cells and mice was determined by immunoblot and immunohistochemistry. AIEC LF82 and dextran sulfate sodium were administrated into C57BL/6 mice for estabolishing inflammatory bowel disease model and for therapeutic study. FINDINGS: O-GlcNAc was increased in intestinal epithelial tissues of CD patients and AIEC LF82-infected mice. Infection of AIEC LF82 up-regulated the level of UDP-GlcNAc and increased O-GlcNAc in human colon epithelial HCT116 and HT-29 cells. We identified that IKKß and NF-κB were O-Glycosylated in AIEC LF82-treated cells. Mutations of IKKß (S733A) and p65 (T352A) abrogated the O-GlcNAc in IKKß and NF-κB and inhibited AIEC LF82-induced activation of NF-κB. Application of 6-diazO-5-oxO-L-norleucine, an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAc, inactivated NF-κB in AIEC LF82-infected cells, enhanced the formation of autophagy, promoted the removal of cell-associated AIEC LF82, alleviated intestinal epithelial inflammation, and improved the survival of the colitis mice. INTERPRETATION: Intestinal inflammation in CD is associated with increased O-GlcNAc modification, which is required for NF-κB activation and suppression of autophagy. Targeting O-GlcNAc could be an effective therapy for inflammatory bowel disease. FUNDING: National Natural Science Foundation of China (Nos. 81573087 and 81772924) and International Cooperation Foundation of Jilin Province (20190701006GH).


Assuntos
Acetilglucosamina/metabolismo , Doença de Crohn/metabolismo , NF-kappa B/metabolismo , Processamento de Proteína Pós-Traducional , Acetilação , Animais , Autofagia , Feminino , Células HCT116 , Células HT29 , Humanos , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
14.
J Cardiothorac Surg ; 15(1): 17, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931838

RESUMO

BACKGROUND: Coronary artery aneurysm is a rare condition which constitutes a small proportion of coronary artery disease. Such condition mimicking an intra-cardiac mass is extremely rare and poorly understood. CASE PRESENTATION: We present an unusual case of a 53-year-old female with decreased exercise tolerance and lower extremity edema for 3 months. The echocardiography showed moderate tricuspid regurgitation and a right intra-ventricular mass below the tricuspid valve. No ventricular wall akinesia or ST segment change was found on echocardiography or electrocardiogram. Coronary computed tomographic angiography confirmed the diagnosis of intra-ventricular mass with feeding vessel originated from the right coronary artery. The patient was scheduled for tumor resection, and the mass turned out to be a thrombosed giant right coronary artery aneurysm. The patient received successful aneurysm resection and had an uneventful postoperative recovery. Unfortunately, a fistula between right coronary artery and right ventricle was detected on follow-up three months later by echocardiography. CONCLUSIONS: Coronary artery aneurysms presenting as intra-cardiac masses are extremely rare. Comprehensive preoperative evaluation is highly recommended because the surgical strategies for tumor and aneurysm are completely different. Aneurysm resection with bypass surgery is preferred rather than aneurysm repair. To our best knowledge, coronary artery aneurysms presenting as intra-ventricular masses have seldom been reported.


Assuntos
Aneurisma Coronário/diagnóstico , Doença da Artéria Coronariana/diagnóstico , Neoplasias Cardíacas/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade
15.
Arch Biochem Biophys ; 680: 108239, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31881189

RESUMO

c-Met receptor is frequently overexpressed in hepatocellular carcinoma and thus considered as an attractive target for pharmacological intervention with small molecule tyrosine kinase inhibitors. Albeit with the development of multiple c-Met inhibitors, none reached clinical application in the treatment of hepatoma so far. To improve the efficacy of c-Met inhibitors towards hepatocellular carcinoma, we investigated the combined effects of the dynamin inhibitor dynasore with several c-Met inhibitors, including tivantinib, PHA-665752, and JNJ-38877605. We provide several lines of evidence that dynasore enhanced the inhibitory effects of these inhibitors on hepatoma cell proliferation and migration, accompanied with increased cell cycle arrest and apoptosis. Mechanically, the combinatorial treatments decreased c-Met levels and hence markedly disrupted downstream signaling, as revealed by the dramatically declined phosphorylation of AKT and MEK. Taken together, our findings demonstrate that the candidate agent dynasore potentiated the inhibitory effects of c-Met inhibitors against hepatoma cells and will shed light on the development of novel therapeutic strategies to target c-Met in the clinical management of hepatocellular carcinoma patients.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Hidrazonas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Carcinoma Hepatocelular/metabolismo , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo
16.
Zhongguo Zhen Jiu ; 40(12): 1374-8, 2020 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-33415885

RESUMO

OBJECTIVE: To analyze the rules of acupoint selection in the treatment of gastroesophageal reflux disease in China using data mining technology. METHODS: The published literature of treating gastroesophageal reflux disease with acupuncture was retrieved from electronic databases from January 1, 1983 to December 1, 2019, including SinoMed, CNKI, Wanfang and VIP database. Acupuncture prescription database was established, and the rules of acupoint selection were explored by statistical software SPSS 20.0 and SPSS Modeler 18.0. RESULTS: A total of 92 articles were included into this analysis, involving 92 acupuncture prescriptions, 76 acupoints. The total frequency of using these acupoints reached 549 times. Zhongwan (CV 12) was the most frequently used acupoint; the often selected meridians were conception vessel, stomach meridian, governor vessel, bladder meridian; the acupoints located at the abdomen, lower limbs and back were commonly selected; crossing points in the specific acupoints were commonly selected; the most frequently used group was Zusanli (ST 36)-Zhongwan (CV 12) and Neiguan (PC 6). CONCLUSION: Treating gastroesophageal reflux disease by acupuncture in China is dominated by shu-mu point combination, supplemented by mu-he point combination; yin meridians are emphasized as much as yang meridians; using specific acupoints is advocated, especially the crossing points.


Assuntos
Terapia por Acupuntura , Refluxo Gastroesofágico , Meridianos , Pontos de Acupuntura , China , Mineração de Dados , Refluxo Gastroesofágico/terapia , Humanos
17.
Fish Shellfish Immunol ; 87: 679-687, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30731213

RESUMO

Ferritins play vital roles in maintenance of iron homeostasis as iron storage proteins. Recently, the immune function of ferritins have attracted increasing attention, especially their roles in defense against pathogenic infections. However, the immune regulatory mechanism of fish ferritins are not well known. In the present study, comparative digital gene expression (DGE) profiling was performed to explore the regulatory effects of the Megalobrama amblycephala ferritins (MamFers) using MamFers overexpressed and control L8824 cells (Ctenopharyngodon idella hepatic cell line). Clean reads were aligned to the C. idella genome and differential expression analysis was conducted with representative differentially expressed genes pointed out. On that basis, further studies were performed to verify two pivotal regulated pathways in L8824 and EPC (Epithelioma Papulosum Cyprini cell line) cells, respectively. The results showed that NLRC5 (NOD-like Receptor Family CARD Domain Containing 5) mediated the regulation of MamFers on expression of MHC I (Major Histocompatibility Complex Class I) and its chaperone ß2M (Beta-2-Microglobulin) in L8824 cells. Then, ß2M further mediated the regulation of MamFers on hepcidin expression, indicating that MamFers regulated the expression of hepcidin via NLRC5/MHC I/ß2M axis. In addition, MamFers regulated the adhesion of Aeromonas hydrophila to EPC cells by regulating the expression of two extracellular matrix proteins Intgß1 (integrin ß1) and FN (fibronectin). In a word, the present study provided novel insights into the immune regulatory functions of fish ferritins.


Assuntos
Cyprinidae/genética , Cyprinidae/imunologia , Ferritinas/genética , Ferritinas/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Aeromonas hydrophila/fisiologia , Animais , Aderência Bacteriana , Carpas , Linhagem Celular , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária
18.
Oncotarget ; 9(2): 1885-1897, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29416738

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Mutations of TP53 may reach 70% - 85% in HNSCC patients without human papillomavirus (HPV) infection. Recurrence rate remains particularly high for HNSCC patients with mutations in the TP53 gene although patients are responsive to surgery, irradiation, and chemotherapy early in the treatment. p53-Reactivation and Induction of Massive Apoptosis-1 (PRIMA-1) and its methylated analogue PRIMA-1Met (also known as APR-246) are quinuclidine compounds that rescue the DNA-binding activity of mutant p53 (mut-p53) and restore the potential of wild-type p53. In the current report, we demonstrated that inhibition of poly (ADP-ribose) polymerase-1 (PARP-1) with 6(5H)-phenanthridinone (PHEN) and N-(6-Oxo-5,6-dihydrophenanthridin-2-yl)-(N, N-dimethylamino) acetamide hydrochloride (PJ34) sensitizes UMSCC1, UMSCC14, and UMSCC17A, three HNSCC cell lines to the treatment of APR-246. PHEN enhances APR-246-induced apoptosis, but not programmed necrosis or autophagic cell death in HNSCC cells. The PARP-1 inhibition-induced sensitization of HNSCC cells to APR-246 is independent of TP53 mutation. Instead, PARP-1 inhibition promotes APR-246-facilitated inactivation of thioredoxin reductase 1 (TrxR1), leading to ROS accumulation and DNA damage. Overexpression of TrxR1 or application of antioxidant N-acetyl-L-cysteine (NAC) depletes the ROS increase, reduces DNA damage, and decreases cell death triggered by APR-246/PHEN in HNSCC cells. Thus, we have characterized a new function of PARP-1 inhibitor in HNSCC cells by inactivation of TrxR1 and elevation of ROS and provide a novel therapeutic strategy for HNSCC by the combination of PARP-1 inhibitors and APR-246.

19.
Oncogene ; 37(25): 3384-3398, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29348462

RESUMO

TP53 mutations frequently occur in head and neck squamous cell carcinoma (HNSCC) patients without human papillomavirus infection. The recurrence rate for these patients is distinctly high. It has been actively explored to identify agents that target TP53 mutations and restore wild-type (WT) TP53 activities in HNSCC. PRIMA-1 (p53-reactivation and induction of massive apoptosis-1) and its methylated analogue PRIMA-1Met (also called APR-246) were found to be able to reestablish the DNA-binding activity of p53 mutants and reinstate the functions of WT p53. Herein we report that piperlongumine (PL), an alkaloid isolated from Piper longum L., synergizes with APR-246 to selectively induce apoptosis and autophagic cell death in HNSCC cells, whereas primary and immortalized mouse embryonic fibroblasts and spontaneously immortalized non-tumorigenic human skin keratinocytes (HaCat) are spared from the damage by the co-treatment. Interestingly, PL-sensitized HNSCC cells to APR-246 are TP53 mutation-independent. Instead, we demonstrated that glutathione S-transferase pi 1 (GSTP1), a GST family member that catalyzes the conjugation of GSH with electrophilic compounds to fulfill its detoxification function, is highly expressed in HNSCC tissues. Administration of PL and APR-246 significantly suppresses GSTP1 activity, resulting in the accumulation of ROS, depletion of GSH, elevation of GSSG, and DNA damage. Ectopic expression of GSTP1 or pre-treatment with antioxidant N-acetyl-L-cysteine (NAC) abrogates the ROS elevation and decreases DNA damage, apoptosis, and autophagic cell death prompted by PL/APR-246. In addition, administration of PL and APR-246 impedes UMSCC10A xenograft tumor growth in SCID mice. Taken together, our data suggest that HNSCC cells are selectively sensitive to the combination of PL and APR-246 due to a remarkably synergistic effect of the co-treatment in the induction of ROS by suppression of GSTP1.


Assuntos
Carcinoma de Células Escamosas/patologia , Dioxolanos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glutationa S-Transferase pi/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Quinuclidinas/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Proliferação de Células , Quimioterapia Combinada , Feminino , Seguimentos , Glutationa S-Transferase pi/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Camundongos , Camundongos SCID , Prognóstico , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Heart Surg Forum ; 21(6): E464-E465, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30604668

RESUMO

Left atrial appendage aneurysm (LAAA) is a rare anomaly, which predisposes to hazardous cardiovascular events. We present a rare case of a 26-year-old female with a giant left atrial appendage aneurysm. The left atrial appendage was incidentally detected during her pregnancy. Six months later after her parturition, the patient was referred to our department and successfully received surgical treatment prophylactically to prevent potential complications. To the best of our knowledge, only about 100 cases of LAAA have been reported.


Assuntos
Apêndice Atrial/cirurgia , Aneurisma Cardíaco/cirurgia , Adulto , Apêndice Atrial/diagnóstico por imagem , Ecocardiografia , Feminino , Aneurisma Cardíaco/complicações , Aneurisma Cardíaco/diagnóstico por imagem , Humanos , Achados Incidentais , Imageamento por Ressonância Magnética , Gravidez , Complicações na Gravidez/diagnóstico por imagem , Complicações na Gravidez/cirurgia , Tomografia Computadorizada por Raios X
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