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Spiders host a diverse range of bacteria in their guts and other tissues, which have been found to play a significant role in their fitness. This study aimed to investigate the community diversity and functional characteristics of spider-associated bacteria in four tissues of Heteropoda venatoria using HTS of the 16S rRNA gene and culturomics technologies, as well as the functional verification of the isolated strains. The results of HTS showed that the spider-associated bacteria in different tissues belonged to 34 phyla, 72 classes, 170 orders, 277 families, and 458 genera. Bacillus was found to be the most abundant bacteria in the venom gland, silk gland, and ovary, while Stenotrophomonas, Acinetobacter, and Sphingomonas were dominant in the gut microbiota. Based on the amplicon sequencing results, 21 distinct cultivation conditions were developed using culturomics to isolate bacteria from the ovary, gut, venom gland, and silk gland. A total of 119 bacterial strains, representing 4 phyla and 25 genera, with Bacillus and Serratia as the dominant genera, were isolated. Five strains exhibited high efficiency in degrading pesticides in the in vitro experiments. Out of the 119 isolates, 28 exhibited antibacterial activity against at least one of the tested bacterial strains, including the pathogenic bacteria Staphylococcus aureus, Acinetobacter baumanii, and Enterococcus faecalis. The study also identified three strains, GL312, PL211, and PL316, which exhibited significant cytotoxicity against MGC-803. The crude extract from the fermentation broth of strain PL316 was found to effectively induce apoptosis in MGC-803 cells. Overall, this study offers a comprehensive understanding of the bacterial community structure associated with H. venatoria. It also provides valuable insights into discovering novel antitumor natural products for gastric cancer and xenobiotic-degrading bacteria of spiders.
Assuntos
Bactérias , Sequenciamento de Nucleotídeos em Larga Escala , RNA Ribossômico 16S , Aranhas , Animais , Aranhas/microbiologia , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , RNA Ribossômico 16S/genética , Feminino , Microbioma Gastrointestinal , Humanos , Filogenia , Biodiversidade , Antibacterianos/farmacologia , PraguicidasRESUMO
The transdifferentiation from cardiac fibroblasts to myofibroblasts is an important event in the initiation of cardiac fibrosis. However, the underlying mechanism is not fully understood. Circ-sh3rf3 (circular RNA SH3 domain containing Ring Finger 3) is a novel circular RNA which was induced in hypertrophied ventricles by isoproterenol hydrochloride, and our work has established that it is a potential regulator in cardiac hypertrophy, but whether circ-sh3rf3 plays a role in cardiac fibrosis remains unclear, especially in the conversion of cardiac fibroblasts into myofibroblasts. Here, we found that circ-sh3rf3 was down-regulated in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes as well as during fibroblast differentiation into myofibroblasts. We further confirmed that circ-sh3rf3 could interact with GATA-4 proteins and reduce the expression of GATA-4, which in turn abolishes GATA-4 repression of miR-29a expression and thus up-regulates miR-29a expression, thereby inhibiting fibroblast-myofibroblast differentiation and myocardial fibrosis. Our work has established a novel Circ-sh3rf3/GATA-4/miR-29a regulatory cascade in fibroblast-myofibroblast differentiation and myocardial fibrosis, which provides a new therapeutic target for myocardial fibrosis.
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Cardiomiopatias , Fibroblastos , Fibrose , Miofibroblastos , RNA Circular , Animais , Ratos , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Fibroblastos/metabolismo , Fibrose/genética , Fibrose/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Miofibroblastos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Z-DNA-binding protein 1 (ZBP1) is an innate sensor of influenza A virus (IAV) that participates in IAV-induced programmed cell death. Nevertheless, little is known about the upstream signaling pathways regulating ZBP1. We found that a member of the tripartite motif (TRIM) family, TRIM34, interacted with ZBP1 to promote its K63-linked polyubiquitination. Using a series of genetic approaches, we provide in vitro and in vivo evidence indicating that IAV triggered cell death and inflammatory responses via dependent on TRIM34/ZBP1 interaction. TRIM34 and ZBP1 expression and interaction protected mice from death during IAV infection owing to reduced inflammatory responses and epithelial damage. Additionally, analysis of clinical samples revealed that TRIM34 associates with ZBP1 and mediates ZBP1 polyubiquitination in vivo. Higher levels of proinflammatory cytokines correlated with higher levels of ZBP1 in IAV-infected patients. Taken together, we conclude that TRIM34 serves as a critical regulator of IAV-induced programmed cell death by mediating the K63-linked polyubiquitination of ZBP1.
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Proteínas de Transporte , Vírus da Influenza A , Proteínas de Ligação a RNA , Animais , Apoptose , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Vírus da Influenza A/metabolismo , Influenza Humana/metabolismo , Camundongos , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/virologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , UbiquitinaçãoRESUMO
BACKGROUND: Family members are currently the main caregivers of the disabled elderly people at home. With declining health and increasing frailty, caregiving of disabled elderly people becomes a task of family caregivers in conjunction with community nurses. Interaction between family caregivers and community nurses can effectively improve the quality of home care for the disabled elderly people. This study aimed to investigate the interaction experiences between family caregivers and community nurses for disabled elderly people at home. METHODS: This research was a study of qualitative descriptions based on semi-structured face-to-face interviews. This study was to purposefully select family caregivers of the disabled elderly and community nurses in Zhengzhou city, Henan Province and explore the interaction patterns between them. Directed content analysis method was used to generate qualitative codes and identify themes. RESULTS: A total of 12 interviews were completed, including 7 family caregivers and 5 community nurses. Four themes were identified: 1) Information interaction; 2) Emotional interaction; 3) Practical interaction; 4) Factors that promote and hinder the interaction. CONCLUSIONS: It was found that the interaction between family caregivers and community nurses was not optimistic. Lack of communication and collaboration between community nurses and caregivers. Providing a new perspective that we can develop and implement intervention to facilitate positive interactions, which will reduce the burden of family caregivers, bring the highest quality of care to older adults with disabilities and improve the quality of care for disabled elderly people. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry on April 19, 2021, number ChiCTR2100045584.
Assuntos
Pessoas com Deficiência , Serviços de Assistência Domiciliar , Humanos , Idoso , Cuidadores/psicologia , Família/psicologia , Pesquisa QualitativaRESUMO
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has already become a global pandemic as a public health emergency of international concern. Previous evidence from similar patient populations proved that carefully selected patients with severe ARDS who did not benefit from conventional treatment might be successfully supported with Veno-Venous extracorporeal membrane oxygenation (V-V ECMO). We now share the case reports of COVID-19 patients with ECMO combined prone position strategies.
Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , COVID-19/terapia , Humanos , Decúbito Ventral , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2RESUMO
BACKGROUND: Circular RNAs (circRNAs) could participate in cis-dichlorodiammineplatinum (DDP) resistance of human cancers. However, circRNAs role in DDP resistance of oral squamous cell carcinoma (OSCC) progression remains largely undeveloped. Here, we attempted to explore the role of circ-SCMH1 (ID hsa_circ_0011946) in acquired DDP resistance. METHODS: Expression of circ-SCMH1, microRNA (miR)-338-3p and Lin-28 homolog B (LIN28B) was detected by real-time quantitative PCR and western blotting, and their interactions were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assay. DDP resistance was assessed by MTT assay, colony formation assay, flow cytometry, transwell assays, western blotting, and xenograft experiment. Transmission electron microscopic analysis, nanoparticle tracking analysis and western blotting confirmed the characterizations of extracellular vesicles (EVs). RESULTS: Circ-SCMH1 was upregulated in DDP-resistant OSCC tissues and cells (SCC-15/DDP and CAL-27/DDP). Circ-SCMH1 knockdown suppressed the half-maximal inhibitory concentration of DDP, colony formation, and migration/invasion in SCC-15/DDP and CAL-27/DDP cells, but promoted apoptosis rate and apoptotic proteins (Bax and cleaved-caspase-3) expression. However, silencing miR-338-3p abrogated above effects, and overexpressing miR-338-3p mimicked that. Similarly, miR-338-3p overexpression role could be counteracted by restoring LIN28B. Moreover, interfering circ-SCMH1 retarded tumor growth of SCC-15/DDP cells in vivo with DDP treatment or not. Mechanistically, circ-SCMH1 directly sponged miR-338-3p in regulating LIN28B, a target gene for miR-338-3p. Notably, circ-SCMH1 was an EVs cargo, and DDP-resistant OSCC cells-derived EVs could provoke circ-SCMH1 upregulation in parental cells. CONCLUSION: Circ-SCMH1 contributes to chemoresistance of DDP-resistant OSCC cells partially via EVs secretion and circ-SCMH1/miR-338-3p/LIN28B axis.
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Objective. To compare the clinical outcomes associated with successful percutaneous coronary intervention (PCI) versus initial medical therapy (MT) in patients with coronary chronic total occlusions (CTOs). Methods. Between January 2007 and December 2016, a total of 1702 patients with ≥1 CTO were enrolled. Patients who had a failed CTO-PCI were excluded. After exclusion, 1294 patients with 1520 CTOs were divided into the MT group initially (did not undergo a CTO-PCI attempt) (n = 800) and successful PCI group (n = 494). Propensity-score matching was also performed to adjust for baseline characteristics. The primary outcome was cardiac death. Results. The median overall follow-up duration was 3.6 (IQR, 2.1-5.0) years, there was no significant difference between the two groups with respect to the prevalence of cardiac death (MT vs. successful PCI: 6.6 vs. 3.8%, adjusted hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.41-2.14, p = .867). In the propensity-matched population (286 pairs), there were no significant differences in the prevalence of cardiac death (MT vs. successful PCI: 5.9% vs. 3.1%, HR 0.51, 95% CI 0.23-1.15, p = .104) and major adverse cardiovascular events (MACE) (HR 0.76, 95% CI 0.53-1.09, p = .130) between the two groups. Conclusion. In the treatment of patients with CTOs, successful PCI is not associated with improved long-term cardiovascular survival or reduced the risk of MACE compared with MT alone initially.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Oclusão Coronária/terapia , Intervenção Coronária Percutânea , Idoso , Fármacos Cardiovasculares/efeitos adversos , Doença Crônica , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Circulating monocytes play a critical role in the pathogenesis of atherosclerosis. Monocyte homing to sites of atherosclerosis is primarily initiated by selectin. Thus, blockade of the interaction of selectins and their ligands holds a significant role in monocyte homing which might be a potential approach to treat atherosclerosis. Here, we investigated the efficacy of a novel peptide analogue of selectin ligands IELLQAR in atherosclerosis. METHODS AND RESULTS: In this study, we firstly measured the effect of the IELLQAR selectin-binding peptide on the inhibition of binding of selectins to monocytes by flow cytometry, which exhibited a dose-dependent inhibitory effect on the binding of the P-, E-, and L-selectins to monocytes, especially the inhibition of P-selectin binding to human peripheral blood monocytes (PBMCs) (half maximal inhibitory concentration (IC50~5 µM)) and THP-1 cells (IC50~10 µM). Furthermore, IELLQAR inhibited P-selectin-induced activation of CD11b on the surface of monocytes and decreased adhesion of monocytes to the endothelium. ApoE-/- mice with or without IELLQAR (1 or 3 mg/kg) fed a Western-type diet (WTD) or which had disturbed blood flow-induced shear stress underwent partial left carotid artery ligation (PLCA) to induce atherosclerosis. In the WTD- and PLCA-induced atherosclerosis models, atherosclerotic plaque formation and monocyte/macrophage infiltration of the arterial wall both decreased in ApoE-/- mice treated with the IELLQAR peptide. Our results also revealed that IELLQAR inhibited the differentiation of monocytes into macrophages through P-selectin-dependent activation of the nuclear factor- (NF-) κB and mammalian target of rapamycin (mTOR) pathways. CONCLUSION: Collectively, our results demonstrated that IELLQAR, a peptide analogue of selectin ligands, inhibited selectin binding to monocytes, which led to subsequent attenuation of atherosclerosis via inhibition of monocyte activation. Hence, use of the IELLQAR peptide provides a new approach and represents a promising candidate for the treatment of atherosclerosis in the early stage of disease.
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Aterosclerose/tratamento farmacológico , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Peptídeos/química , Peptídeos/uso terapêutico , Selectinas/química , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Colesterol/sangue , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Camundongos , Células THP-1 , Triglicerídeos/sangueRESUMO
A growing number of long non-coding RNAs (lncRNAs) have been found to be involved in diverse biological processes such as cell cycle regulation, embryonic development, and cell differentiation. However, limited knowledge is available concerning the underlying mechanisms of lncRNA functions. In this study, we found down-regulation of TCONS_00041960 during adipogenic and osteogenic differentiation of glucocorticoid-treated bone marrow mesenchymal stem cells (BMSCs). Furthermore, up-regulation of TCONS_00041960 promoted expression of osteogenic genes Runx2, osterix, and osteocalcin, and anti-adipogenic gene glucocorticoid-induced leucine zipper (GILZ). Conversely, expression of adipocyte-specific markers was decreased in the presence of over-expressed TCONS_00041960. Mechanistically, we determined that TCONS_00041960 as a competing endogenous RNA interacted with miR-204-5p and miR-125a-3p to regulate Runx2 and GILZ, respectively. Overall, we identified a new TCONS_00041960-miR-204-5p/miR-125a-3p-Runx2/GILZ axis involved in regulation of adipogenic and osteogenic differentiation of glucocorticoid-treated BMSCs.
Assuntos
Adipogenia/genética , Células da Medula Óssea/fisiologia , Células-Tronco Mesenquimais/fisiologia , MicroRNAs/genética , Osteogênese/genética , RNA Longo não Codificante/genética , Adipócitos/fisiologia , Animais , Diferenciação Celular/genética , Regulação para Baixo/genética , Ratos , Ratos Sprague-Dawley , Regulação para Cima/genéticaRESUMO
AIM: Though lutein can inhibit cancer cell proliferation via alleviating oxidative injury, the molecular mechanisms of lutein involvement in the NrF2/antioxidant response element (ARE) and NF-κB pathways remain poorly understood. MATERIALS & METHODS: MTT, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blot assays were performed. RESULTS: After treatment with lutein, breast cancer cell proliferation was significantly decreased in a dose-dependent manner. Lutein induced nuclear translocation and protein expression of NrF2, improved the expression of cellular antioxidant enzymes and attenuated reactive oxygen species levels. Moreover, lutein treatment decreased NF-κB signaling pathway related NF-κB p65 protein expression. CONCLUSION: The effect of lutein antiproliferation was mediated by activation of the NrF2/ARE pathway, and blocking of the NF-κB signaling pathway.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Luteína/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fator de Transcrição RelA/genética , Elementos de Resposta Antioxidante/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: To investigate the effect of paravertebral dexmedetomidine as an adjuvant to ropivacaine on independent lung injury during one-lung ventilation. METHODS: In total, 120 patients who underwent elective radical resection of pulmonary carcinoma were randomly assigned to one of six groups (n = 20): normal saline (C group), ropivacaine (R group), intravenous dexmedetomidine (Div group), 0.5 µg/kg paravertebral dexmedetomidine as an adjuvant to ropivacaine (RD0.5 group), 1.0 µg/kg paravertebral dexmedetomidine as an adjuvant to ropivacaine (RD1.0 group), or 2.0 µg/kg paravertebral dexmedetomidine as an adjuvant to ropivacaine (RD2.0 group). Patients in the R, Div, RD0.5, RD1.0 and RD2.0 groups underwent a thoracic paravertebral block, and normal saline was administered as a control to C group. Small marginal lung samples next to the tumor were harvested immediately after the tumor tissues were excised. Lung injury was evaluated as follows: an injury score was determined via light microscopy, and cell apoptosis was determined via a TUNEL assay. TNF-α, IL-6, miRNA-210, HIF-1α, Tom20 and ISCU2 were also detected. RESULTS: Both intravenous and paravertebral dexmedetomidine attenuated independent lung injury. Downregulation of HIF-1α and miRNA-210 and upregulation of Tom20 and ISCU2 may be the underlying mechanism. No difference was observed between the Div and RD0.5 groups, and no further improvement of lung injury was found in the RD1.0 and RD2.0 groups with increased paravertebral dexmedetomidine doses. CONCLUSIONS: Paravertebral dexmedetomidine as an adjuvant to ropivacaine, which is comparable to intravenous dexmedetomidine, could protect against independent lung injury during one-lung ventilation. TRIAL REGISTRATION: ISRCTN, 13000406 ; retrospectively registered on 22.05.2018.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anestésicos Locais/administração & dosagem , Dexmedetomidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Ventilação Monopulmonar/efeitos adversos , Ropivacaina/administração & dosagem , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Adulto , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Ventilação Monopulmonar/métodos , Estudos RetrospectivosRESUMO
MicroRNAs (miRNAs) can function as oncogenes or tumor suppressor genes and are involved in multiple processes in cancer development and progression. For example, miR-192 is dysregulated in multiple human cancers, including osteosarcoma (OS). However, the pathophysiological role of miR-192 and its relevance to OS cell growth and invasion has not yet been clarified. This study aimed to investigate the expression of miR-192 in OS and elucidate the molecular mechanisms by which miR-192 acts as a tumor suppressor in this disease. The qRT-PCR data identified significant down-regulation of miR-192 in 20 OS tissue samples and two OS cell lines when compared with adjacent normal tissues and a human osteoblast cell line, respectively. Furthermore, Western blot analysis revealed overexpression of T cell-specific transcription factor (TCF) 7 protein in tumor tissues compared with matched adjacent normal tissues. Further in vitro studies demonstrated that enforced expression of miR-192 inhibited U2OS and MG63 cell proliferation, invasion, and migration and induced apoptosis. Finally, Western blot and Luciferase assays identified TCF7 as a target of miR-192. Collectively, these findings suggest an important role for miR-192 in regulating the proliferation, migration, invasion, and apoptosis of OS cells through the regulation of TCF7.
Assuntos
Neoplasias Ósseas/patologia , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/patologia , Fator 1 de Transcrição de Linfócitos T/metabolismo , Apoptose , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Estudos de Casos e Controles , Humanos , Invasividade Neoplásica , Osteossarcoma/genética , Osteossarcoma/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator 1 de Transcrição de Linfócitos T/genética , Células Tumorais CultivadasRESUMO
Genogroup II, genotype 3 noroviruses (GII.3 NoVs) are secondary to GII.4 NoVs in causing acute non-bacterial gastroenteritis worldwide. In our previous study, we found that virus-like particles (VLPs) derived from a GII.3 NoV strain exhibited no binding activity to any salivary and synthetic histo-blood group antigens (HBGAs) tested. In this study, the nucleotide sequence encoding the major capsid protein of another documented GII.3 NoV strain was codon-optimized and synthesized, and the major capsid protein was expressed using recombinant baculovirus virus expression system. The assembly of VLPs was verified by electron microscopy, and the binding profiles of the assembled VLPs to salivary HBGAs were determined, and in vitro VLP-salivary HBGAs binding blockade assay was used to test the cross-blocking effects of hyperimmune sera produced against different genotypes (GI.2, GII.3, and GII.4). The expression of the major capsid proteins led to the successful assembly of VLPs, and in vitro VLP-salivary HBGAs binding assay indicated that the assembled VLPs bound to salivary HBGAs from blood type A, B, AB, and O individuals, with the highest binding capacity to type A salivary HBGAs. In vitro VLP-salivary HBGAs binding blockade assay demonstrated the absence of blocking activities for hyperimmune sera produced against GI.2and GII.4 VLPs and the presence of blocking activity for that against GII.3 VLPs. Our results suggest the absence of cross-blocking activities among different genotypes and the presence of blocking activities between GII.3 NoVs from different clusters, which might have implications for the design of multivalent NoV vaccines.
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Proteínas do Capsídeo/genética , Norovirus/genética , Baculoviridae/genética , Sequência de Bases/genética , Antígenos de Grupos Sanguíneos/genética , Genótipo , Humanos , Receptores Virais/genética , Glândulas Salivares/virologia , Ligação ViralRESUMO
The regulation of cardiac differentiation is critical for maintaining normal cardiac development and function. The precise mechanisms whereby cardiac differentiation is regulated remain uncertain. Here, we have identified a GATA-4 target, EGF, which is essential for cardiogenesis and regulates cardiac differentiation in a dose- and time-dependent manner. Moreover, EGF demonstrates functional interaction with GATA-4 in inducing the cardiac differentiation of P19CL6 cells in a time- and dose-dependent manner. Biochemically, GATA-4 forms a complex with STAT3 to bind to the EGF promoter in response to EGF stimulation and cooperatively activate the EGF promoter. Functionally, the cooperation during EGF activation results in the subsequent activation of cyclin D1 expression, which partly accounts for the lack of additional induction of cardiac differentiation by the GATA-4/STAT3 complex. Thus, we propose a model in which the regulatory cascade of cardiac differentiation involves GATA-4, EGF, and cyclin D1.
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Diferenciação Celular/fisiologia , Fator de Crescimento Epidérmico/metabolismo , Fator de Transcrição GATA4/metabolismo , Coração/embriologia , Modelos Biológicos , Miocárdio/citologia , Transdução de Sinais/fisiologia , Animais , Western Blotting , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Técnicas Histológicas , Imunoprecipitação , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Fatores de TempoRESUMO
It has been reported that the antitumor drug doxorubicin (Dox) exerts its toxic effects via GATA-4 depletion and that over-expression of GATA-4 reverses Dox-induced toxicity and apoptosis; however, the precise mechanisms remain unclear. In this study, we observed, for the first time, that EGF protects cells against Dox-mediated growth arrest, G2/M-phase arrest, and apoptosis. Additionally, EGF expression was down-regulated in Dox-treated cells and up-regulated in GATA-4 over-expressing cells. Utilizing real-time PCR and western blotting analysis, we found that the expression of the cell cycle-associated protein cyclin D1 was inhibited in GATA-4-silenced cells and Dox-treated cells and was enhanced in GATA-4 over-expressing cells and EGF-treated cells. Furthermore, EGF treatment reversed the inhibited expression of cyclin D1 that was mediated by GATA-4 RNAi or Dox. Our results indicate that EGF, as a downstream target of Dox, may be involved in Dox-induced toxicity as well as in the protective role of GATA-4 against toxicity induced by Dox via regulating cyclin D1 expression, which elucidates a new molecular mechanism of Dox toxicity with important clinical implications.
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Antibióticos Antineoplásicos/farmacologia , Ciclina D1/metabolismo , Doxorrubicina/farmacologia , Fator de Crescimento Epidérmico/farmacologia , Fator de Transcrição GATA4/metabolismo , Animais , Apoptose , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fator de Transcrição GATA4/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , CamundongosRESUMO
PURPOSE: The aim of this study was to investigate the changes in oxidative stress and antioxidants in lung tissue under different tidal volume ventilation conditions. METHODS: Forty-eight male Wistar rats were randomized into four groups, namely, group C, the control group, which was not ventilated, and groups C1, C2 and C3, the treatment groups, which were ventilated for 2 h with tidal volumes of 8, 30 and 42 ml/kg, respectively. The right middle lobe was assayed for malondialdehyde (MDA), the right posterior lobe was assayed using Western blotting for Nrf2, GCLm and SrX1 and the left lobe was assayed for Nrf2, GCLm and SrX1 mRNA. RESULTS: The MDA levels were increased in the three treatment groups, with MDA levels highest in group C3 and lowest in group C1 (C3 > C2 > C1) (all P < 0.05). The mRNA expression of Nrf2, GCLm and SrX1 was highest in group C3 and lowest in group 1 (C3 > C2 > C1) (all P < 0.05). No significant difference was observed between group C1 and group C (P > 0.05). A Western blot analysis showed that Nrf2, GCLm and SrX1 expression was highest in group C3 and lowest in group C1 (C3 > C2 > C1) (all P < 0.05). No significant difference was observed between group C1 and group C (P > 0.05). CONCLUSIONS: Oxidative stress and antioxidant enzyme levels in the lungs of rats were positively associated with the tidal volumes of mechanical ventilation, suggesting that higher tidal volumes cause more severe oxidative stress and increased antioxidant responses.
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Antioxidantes/metabolismo , Pulmão/metabolismo , Estresse Oxidativo/fisiologia , Respiração Artificial/métodos , Animais , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Volume de Ventilação Pulmonar/fisiologiaRESUMO
BACKGROUND: Karst caves serve as natural laboratories, providing organisms with extreme and constant conditions that promote isolation, resulting in a genetic relationship and living environment that is significantly different from those outside the cave. However, research on cave creatures, especially Opiliones, remains scarce, with most studies focused on water, soil, and cave sediments. RESULTS: The structure of symbiotic bacteria in different caves were compared, revealing significant differences. Based on the alpha and beta diversity, symbiotic bacteria abundance and diversity in the cave were similar, but the structure of symbiotic bacteria differed inside and outside the cave. Microorganisms in the cave play an important role in material cycling and energy flow, particularly in the nitrogen cycle. Although microbial diversity varies inside and outside the cave, Opiliones in Beijing caves and Hainan Island exhibited a strong similarity, indicating that the two environments share commonalities. CONCLUSIONS: The karst cave environment possesses high microbial diversity and there are noticeable differences among different caves. Different habitats lead to significant differences in the symbiotic bacteria in Opiliones inside and outside the cave, and cave microorganisms have made efforts to adapt to extreme environments. The similarity in symbiotic bacteria community structure suggests a potential similarity in host environments, providing an explanation for the appearance of Sinonychia martensi in caves in the north.
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Bactérias , Cavernas , Ecossistema , Simbiose , Cavernas/microbiologia , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/classificação , China , Microbiota/fisiologia , BiodiversidadeRESUMO
Hepatocellular carcinoma (HCC) is a primary liver cancer with high pathogenicity and extremely poor prognosis. The role of circular RNAs (circRNAs) in HCC carcinogenesis and progression remains to be determined. Based on the analysis of HCC-related databases, as well as the expression analysis and identification of 25 HCC patient tissues and HCC cell lines, we found that the hsa_circ_0031431 (circCOCH) is significantly highly expressed in HCC tissues and cell lines. High circCOCH expression is associated with enhanced tumor proliferation and metastasis, and knocking down circCOCH can inhibit the growth of HCC in vivo and in vitro. Mechanistic studies show that circCOCH upregulates the expression of epidermal growth factor receptor (EGFR) through sponge miR-450a, thereby activating the Phosphoinositide 3-kinases (PI3Ks) cell pathway to promote HCC proliferation and metastasis. Futhermore, we found that IGF2BP3 mediates the biogenesis of circCOCH. The present study provides innovative insights into the role of circRNAs in the etiology of HCC carcinogenesis and might serve as a new promising therapeutic target for HCC.
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Esculetin (Esc), a coumarin derivative and herbal medicinal compound used in traditional Chinese medicine, is extracted from Fraxinus chinensis. Esc has shown notable potential in the inhibition of proliferation, metastasis and cell cycle arrest in various cancer cell lines. The present review is based on research articles regarding Esc in the field of carcinoma, published between 2009 and 2023. These studies have unanimously demonstrated that Esc can effectively inhibit cancer cell proliferation through diverse mechanisms and modulate multiple signaling pathways, such as Wnt/ß-catenin, PI3K/Akt, MAPK and janus kinase/signal transducer and activator of transcription-3. In addition, the safety profile of Esc has been demonstrated in credible animal experiments, which has indicated Esc as an effective compound. Furthermore, the combination therapy of Esc with commonly used chemotherapeutic drugs holds great promise. The aim of the present review was to encourage further studies and applications of Esc in cancer therapy.