RESUMO
In this paper, the preferentially cutting-rewiring operation (PCRO) consisting of the cutting procedure and the rewiring procedure is proposed and is applied on an excitable Erdös-Rényi random network (EERRN), by which the structure of the initially homogeneous network changes dramatically, and lots of common leaves (CLs) are formed between the two hubs. Subsequently, besides the single-mode oscillations that can be usually observed in homogeneous excitable systems, a new kind of multi-mode oscillations composed of synchronous and asynchronous parts can self-organize to emerge, which are similar to the coherent and incoherent clusters in traditional chimera states and are consequently named as the chimeralike oscillation modes (CLOMs). Importantly, by utilizing the dominant phase-advanced driving method, both the mechanisms for the formation and the emergence of CLOMs in EERRNs with PCRO are well explained, among which the CL is exposed to play a key role in forming the CLOMs. Furthermore, the PCRO-induced CLOM phenomena can also be observed in other paradigmatic network models or with other paradigmatic excitable dynamics, which definitely confirms that the PCRO is an universal method in inducing the CLOMs in excitable complex networks. Our contributions may shed lights on a new perspective of the emergence of CLOMs in complex systems and would have great impacts in related fields.
RESUMO
RAD23 (RADIATION SENSITIVE23) proteins are a group of UBL-UBA (ubiquitin-like-ubiquitin-associated) proteins that shuttle ubiquitylated proteins to the 26S proteasome for breakdown. Drought stress is a major environmental constraint that limits plant growth and production, but whether RAD23 proteins are involved in this process is unclear. Here, we demonstrated that a shuttle protein, MdRAD23D1, mediated drought response in apple plants (Malus domestica). MdRAD23D1 levels increased under drought stress, and its suppression resulted in decreased stress tolerance in apple plants. Through in vitro and in vivo assays, we demonstrated that MdRAD23D1 interacted with a proline-rich protein MdPRP6, resulting in the degradation of MdPRP6 by the 26S proteasome. And MdRAD23D1 accelerated the degradation of MdPRP6 under drought stress. Suppression of MdPRP6 resulted in enhanced drought tolerance in apple plants, mainly because the free proline accumulation is changed. And the free proline is also involved in MdRAD23D1-mediated drought response. Taken together, these findings demonstrated that MdRAD23D1 and MdPRP6 oppositely regulated drought response. MdRAD23D1 levels increased under drought, accelerating the degradation of MdPRP6. MdPRP6 negatively regulated drought response, probably by regulating proline accumulation. Thus, "MdRAD23D1-MdPRP6" conferred drought stress tolerance in apple plants.
Assuntos
Malus , Ubiquitina , Ubiquitina/metabolismo , Proteínas de Transporte , Malus/genética , Proteínas de Plantas/genética , Secas , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Plantas Geneticamente Modificadas/metabolismoRESUMO
BACKGROUND: Osteosarcoma (OS) immune environment is complexed and the immune factors-related to OS progression need to be explored. Tumor-associated macrophages (TAMs) are regarded as immune suppressive and tumor-promoting cells. However, the underlying mechanisms through which TAMs function are still fragmentary. Here, we aim to explore the underlying mechanisms by which TAMs regulate OS progression. METHODS: TAMs from OS tissues were isolated by flow cytometry. Exosomes derived from TAMs were separated using ultracentrifugation and western blotting. Transmission electron microscopy (TEM), and flow cytometry were constructed to characterize TAMs-derived exosomes. Additionally, the differential MicroRNAs (miRNAs) and genes were detected through RNA sequencing, and further validated using real-time PCR (RT-PCR). OS cell metastasis ability was assessed using transwell invasion and scratch wound healing assays. MiRNAs mimic and lentiviral vectors were utilized to explore the effects on OS progression. RESULTS: Exosome secreted by TAMs accelerated the OS metastasis. Let-7a level was upregulated in TAMs derived exosomes, which downregulated C15orf41 by targeting 3'-untranslated region (UTR). Furthermore, overexpressing let-7a enhanced invasion and migration by blocking the transcription of C15orf41. In consistent, up-regulating let-7a promoted OS progression and made the prognosis to be worse, which can be reversed by C15orf41 overexpression. CONCLUSION: This study highlighted the critical role of TAMs-derived exosomes in OS progression and explored the potential value of the let-7a/C15orf41 axis as an indicator or target for OS.
Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Humanos , Macrófagos Associados a Tumor/patologia , Linhagem Celular Tumoral , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Proliferação de Células , Regulação Neoplásica da Expressão GênicaRESUMO
To ascertain the effects of Taraxacum mongolicum flavonoids (TMF) on the growth performance, digestive enzyme activity, immune indices, inflammatory response and antioxidant capacity of Channa argus, 400 C. argus with an average body weight of (8.08 ± 0.21) g were selected and divided randomly into four groups. They were fed with four experimental diets supplemented with TMF of 0 (control), 25, 50 and 100 mg/kg for 56 d, and then challenged with lipopolysaccharide (LPS) for 96 h, afterwards indices were detected. The results manifested that the addition of TMF above 50 mg/kg in the dietary could significantly improve the final body weight, WGR, SGR and PER of C. argus, while decreased FCR (P < 0.05). Similarly, the 50 mg/kg group had the highest activity of digestive enzymes (protease, lipase, amylase) in intestine and hepatopancreas, which were notably higher than those in the control group (P < 0.05). Nevertheless, 100 mg/kg group could effectively inhibit the liver and gut injury caused by LPS and reduce the contents of ALT and AST, LPS and LBP in serum. In the immune (LY, AKP, ACP, IgM, C3) and antioxidant (T-AOC, SOD, CAT, GSH-PX, GR, ASA, MDA) systems, 100 mg/kg groups were the optimal group, which were remarkably higher than those of the control group (P < 0.05). Additionally, the expression of genes revealed that 100 mg/kg group could noteworthy restrain the expression of pro-inflammatory factors (tnf-α, il-1ß, il-8) and pro-apoptosis (cas-3,8,9, p53, bax, bcl-2) related genes, up-regulate the expression of anti-inflammatory (il-10, tgf-ß) factors, antioxidant-related (nrf2, gpx, gst, cat) genes and heat shock proteins (hsp70, hsp90). Simultaneously, the survival rate of C. argus in the 100 mg/kg TMF-supplemented group was the highest after LPS challenge. Our results elucidate that dietary supplementation TMF protects C. argus from LPS-induced inflammatory injury, to ameliorate digestion, immune response, antioxidant status and apoptosis, implying that TMF could be regarded as an anti-inflammatory and antioxidant agent adding to aquatic animal feed.
Assuntos
Antioxidantes , Taraxacum , Animais , Ração Animal/análise , Antioxidantes/metabolismo , Apoptose , Peso Corporal , Dieta/veterinária , Suplementos Nutricionais , Flavonoides/farmacologia , Imunidade Inata , Lipopolissacarídeos/farmacologiaRESUMO
The present study established a necroptosis model in vitro and investigated the role of HMGB1 in cell necroptosis. A combination of tumor necrosis factor-α and z-VAD-fmk was used to induce necroptosis in L929 cells with necroptosis inhibitor necrostatin-1 applied as an intervention. Flow cytometry and transmission electron microscopy (TEM) were used to measure cell necroptosis. Western blotting assay was applied to detect the expression of receptor-interacting serine/threonine-protein kinase 3 (RIPK3), mixed lineage kinase domain-like pseudokinase (MLKL) and HMGB1. Co-immunoprecipitation (Co-IP) assay was used to confirm the interaction between HMGB1 and RIPK3. Our study demonstrated that HMGB1 migrated from the nucleus to the cytoplasm at the onset of necroptosis and was subsequently released passively to the extracellular matrix. Further experiments determined that the binding of HMGB1 with RIPK3 in the cytoplasm was loose during necroptosis. By contrast, when necroptosis was inhibited, the interaction in the cytoplasm was tight suggesting that this association between HMGB1 and RIPK3 might affect its occurrence. In conclusion, the transfer of HMGB1 from nucleus to cytoplasm, and its interaction with RIPK3 might be potentially involved in necroptosis.
Assuntos
Proteína HMGB1 , Necroptose , Proteína Serina-Treonina Quinases de Interação com Receptores , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Apoptose , Linhagem Celular , Citoplasma/metabolismo , Proteína HMGB1/metabolismo , Camundongos , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND: Intracranial aneurysms associated with cerebral arteriovenous malformations (AVMs) are a rare condition in the clinic, and treatment is very difficult due to their particular anatomical features. We present our experience in the treatment of intracranial aneurysms with AVMs and evaluate the effectiveness and safety of endovascular treatment combined with microsurgical resection (the hybrid operation). METHODS: This was a single-center retrospective study in our neurosurgical department from January 2015 to January 2021. We collected clinical data from 48 patients with intracranial aneurysms associated with AVMs and categorized them according to Redekop classifications according to the results of cerebral imaging examination to compare the therapeutic effects of endovascular embolization and the hybrid operation. RESULTS: Compared to nonaneurysmal AVMs, intracranial aneurysms with AVMs more often presented with intracranial hemorrhage (P<0.05). Massive hematoma and severe neurological impairment were more often found in patients with intracranial aneurysms with AVMs (P<0.05). For flow-related aneurysms, the hybrid surgery had a higher one-stage cure rate than endovascular embolization alone (P<0.05). Both treatment methods had similar effects on intranidal aneurysms (P>0.05). There were no significant differences in prognostic indicators between the two treatments. However, the recurrence rate of AVMs with proximal flow-related aneurysms was lower in patients who underwent the hybrid operation (P<0.05). CONCLUSION: The hybrid operation was safe and effective for patients with intracranial aneurysms associated with AVMs. For flow-related aneurysms, the one-stage cure rate was higher and the recurrence rate was lower with the hybrid operation than with endovascular embolization alone.
Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Malformações Arteriovenosas Intracranianas , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/cirurgia , Hemorragias Intracranianas/terapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Itaconate, a metabolite of the tricarboxylic acid cycle, plays anti-inflammatory roles in macrophages during endotoxemia. The mechanisms underlying its anti-inflammatory roles have been shown to be mediated by the modulation of oxidative stress, an important mechanism of hepatic ischemia-reperfusion (I/R) injury. However, the role of itaconate in liver I/R injury is unknown. APPROACH AND RESULTS: We found that deletion of immune-responsive gene 1 (IRG1), encoding for the enzyme producing itaconate, exacerbated liver injury and systemic inflammation. Furthermore, bone marrow adoptive transfer experiments indicated that deletion of IRG1 in both hematopoietic and nonhematopoietic compartments contributes to the protection mediated by IRG1 after I/R. Interestingly, the expression of IRG1 was up-regulated in hepatocytes after I/R and hypoxia/reoxygenation-induced oxidative stress. Modulation of the IRG1 expression levels in hepatocytes regulated hepatocyte cell death. Importantly, addition of 4-octyl itaconate significantly improved liver injury and hepatocyte cell death after I/R. Furthermore, our data indicated that nuclear factor erythroid 2-related factor 2 (Nrf2) is required for the protective effect of IRG1 on mouse and human hepatocytes against oxidative stress-induced injury. Our studies document the important role of IRG1 in the acute setting of sterile injury induced by I/R. Specifically, we provide evidence that the IRG1/itaconate pathway activates Nrf2-mediated antioxidative response in hepatocytes to protect liver from I/R injury. CONCLUSIONS: Our data expand on the importance of IRG1/itaconate in nonimmune cells and identify itaconate as a potential therapeutic strategy for this unfavorable postsurgical complication.
Assuntos
Anti-Inflamatórios/farmacologia , Carboxiliases/fisiologia , Hepatócitos/metabolismo , Fígado/irrigação sanguínea , Fator 2 Relacionado a NF-E2/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Succinatos/farmacologia , Animais , Humanos , Hidroliases/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Transdução de Sinais/fisiologia , Succinatos/uso terapêuticoRESUMO
Nonalcoholic fatty liver disease (NAFLD) is regarded as a threat to public health; however, the pathologic mechanism of NAFLD is not fully understood. We attempted to identify abnormally expressed long noncoding RNA (lncRNAs) and messenger RNA that may affect the occurrence and development of NAFLD in this study. The expression of differentially expressed lncRNAs in NAFLD was determined in oleic acid (OA)-treated L02 cells, and the functions of CCAT1 in lipid droplet formation were evaluated in vitro. Differentially expressed genes (DEGs) were analyzed by microarray analysis, and DEGs related to CCTA1 were selected and verified by weighted correlation network analysis. The dynamic effects of LXRα and CCTA1 on lipid droplet formation and predicted binding was examined. The binding between miR-631 and CCAT1 and LXRα was verified. The dynamic effects of miR-613 inhibition and CCTA1 silencing on lipid droplet formation were examined. The expression and correlations of miR-631, CCAT1, and LXRα were determined in tissue samples. As the results show, CCAT1 was induced by OA and upregulated in NAFLD clinical samples. CCAT1 silencing significantly suppressed lipid droplet accumulation in vitro. LXRα was positively correlated with CCAT1. By inhibiting miR-613, CCAT1 increased the transcription of LXRα and promoted LXRα expression. The expression of LXRα was significantly increased in NAFLD tissues and was positively correlated with CCAT1. In conclusion, CCAT1 increases LXRα transcription by serving as a competing endogenous RNA for miR-613 in an LXRE-dependent manner, thereby promoting lipid droplet formation and NAFLD. CCAT1 and LXRα might be potent targets for NAFLD treatment.
Assuntos
Receptores X do Fígado/genética , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação da Expressão Gênica/genética , Humanos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Transcrição Gênica/genéticaRESUMO
BACKGROUND: The transmission features and the feasibility of containing shigellosis remain unclear among a population-based study in China. METHODS: A population-based Susceptible - Exposed - Infectious / Asymptomatic - Recovered (SEIAR) model was built including decreasing the infectious period (DIP) or isolation of shigellosis cases. We analyzed the distribution of the reported shigellosis cases in Hubei Province, China from January 2005 to December 2017, and divided the time series into several stages according to the heterogeneity of reported incidence during the period. In each stage, an epidemic season was selected for the modelling and assessing the effectiveness of DIP and case isolation. RESULTS: A total of 130,770 shigellosis cases were reported in Hubei Province. The median of Reff was 1.13 (range: 0.86-1.21), 1.10 (range: 0.91-1.13), 1.09 (range: 0.92-1.92), and 1.03 (range: 0.94-1.22) in 2005-2006 season, 2010-2011 season, 2013-2014 season, and 2016-2017 season, respectively. The reported incidence decreased significantly (trend χ2 = 8260.41, P < 0.001) among four stages. The incidence of shigellosis decreased sharply when DIP implemented in three scenarios (γ = 0.1, 0.1429, 0.3333) and when proportion of case isolation increased. CONCLUSIONS: Year heterogeneity of reported shigellosis incidence exists in Hubei Province. It is feasible to contain the transmission by implementing DIP and case isolation.
Assuntos
Disenteria Bacilar/epidemiologia , Epidemias , Modelos Teóricos , Infecções Assintomáticas , China/epidemiologia , Simulação por Computador , Coleta de Dados , Disenteria Bacilar/prevenção & controle , Disenteria Bacilar/transmissão , Estudos de Viabilidade , Humanos , Incidência , Estações do AnoRESUMO
In the current experiment, the effects of transforming growth factor (TGF)-ß1/Smad and ERK pathway crosstalk on synovial and pulmonary systems during rheumatoid arthritis have been investigated. For this purpose, rats were divided into normal control (NC) and model control (MC) groups. In the MC group, 0.1 ml Freund's complete adjuvant was injected intradermally into the right hind paw, and the resulting inflammation represented a rheumatoid arthritis model. Joint swelling and changes in lung functions were observed in arthritic rats. Synovial and lung were observed by light and electron microscopies. Enzyme-linked immunosorbent assays were used to detect TGF-ß1, interleukin (IL)-1ß, IL-4, IL-10, interferon-γ (IFN-γ), connective tissue growth factor (CTGF), and fibroblast growth factor (FGF). PCR, immunohistochemistry, and immunoblotting were used to detect changes in Smad and ERK pathways of synovial and lung tissues. Compared with the NC group, toe swelling was elevated in the MC group. Pulmonary functions FEV1, FEF50, FEF75, MMF, and PEF were decreased (P< 0.01). Serum cytokines IL-1ß, IL-4, TGF-ß1, and CTGF were increased, while IFN-γ, IL-10, Th1/Th2 cell ratio, and FGF were decreased (P< 0.01 or P< 0.05). Expression of TGF-ß1 and Smad2/3/4 mRNAs and TGF-ß1, TßRI, TßRII, Smad2/3, p-Smad2/3, and Smad4 proteins in the synovial membrane and lung tissue were increased, and expression of Smad7 mRNA and protein was decreased (P<0.01) or P<0.05). Expression of ERK2 mRNA and p-ERK1/2 protein was increased in the synovial membrane and lung tissue, and expression of ERK1/2 mRNAs and ERK1/2 and p-ERK1/2 proteins was increased in lung tissue (P< 0.01 or P< 0.05). Correlation analysis showed that FEV1 was negatively correlated with TGF-ß1 mRNA and protein in arthritic rats, FEF25 was negatively correlated with Smad4 protein, and FEF50 was negatively correlated with the TßRII protein, and FEF75, TGF-ß1 and Smad3 mRNAs. There was a negative correlation between Smad2/3 protein and a negative correlation between PEF and TGF-ß1 protein (P< 0.05). FEF50 and MMF were positively correlated with Smad7 mRNA (P< 0.05). FEV1 was negatively correlated with ERK2 mRNA, and FEF25 was negatively correlated with p-ERK1/2 protein. FEF75 and MMF were negatively correlated with ERK1/2 and p-ERK1/2, respectively (P< 0.05). ERK1 mRNA was positively correlated with Smad3 mRNA and TßRII protein, ERK2 mRNA was positively correlated with p-Smad2/3, and ERK1/2 protein was positively correlated with Smad2 mRNA, Smad4 protein, p-ERK1/2 protein, Smad4 mRNA, and p-Smad2/3 protein (P< 0.05). p-ERK1/2 protein was negatively correlated with Smad7 protein (P< 0.05). It is concluded that arthritic rats have synovial and systemic pulmonary damage. Smad and ERK pathway crosstalk leads to systemic lesions. Smad and ERK pathways are gradually activated by phosphorylation under the induction of the TGF-ß1 promoter, and then participate in transcriptional activities, leading to the increase in synovial inflammation of arthritis, pulmonary lesions, and decreases in lung functions.
Assuntos
Artrite Reumatoide/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Pulmão/fisiopatologia , Proteínas Smad/metabolismo , Membrana Sinovial/fisiopatologia , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/genética , Adjuvante de Freund/toxicidade , Pulmão/metabolismo , Masculino , Ratos , Ratos Wistar , Testes de Função Respiratória , Transdução de Sinais , Proteínas Smad/genética , Membrana Sinovial/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
We show that NITRATE REGULATORY GENE2 (NRG2), which we identified using forward genetics, mediates nitrate signaling in Arabidopsis thaliana. A mutation in NRG2 disrupted the induction of nitrate-responsive genes after nitrate treatment by an ammonium-independent mechanism. The nitrate content in roots was lower in the mutants than in the wild type, which may have resulted from reduced expression of NRT1.1 (also called NPF6.3, encoding a nitrate transporter/receptor) and upregulation of NRT1.8 (also called NPF7.2, encoding a xylem nitrate transporter). Genetic and molecular data suggest that NRG2 functions upstream of NRT1.1 in nitrate signaling. Furthermore, NRG2 directly interacts with the nitrate regulator NLP7 in the nucleus, but nuclear retention of NLP7 in response to nitrate is not dependent on NRG2. Transcriptomic analysis revealed that genes involved in four nitrogen-related clusters including nitrate transport and response to nitrate were differentially expressed in the nrg2 mutants. A nitrogen compound transport cluster containing some members of the NRT/PTR family was regulated by both NRG2 and NRT1.1, while no nitrogen-related clusters showed regulation by both NRG2 and NLP7. Thus, NRG2 plays a key role in nitrate regulation in part through modulating NRT1.1 expression and may function with NLP7 via their physical interaction.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Nitratos/metabolismo , Nitrogênio/metabolismo , Transdução de Sinais , Proteínas de Transporte de Ânions/genética , Proteínas de Transporte de Ânions/metabolismo , Arabidopsis/citologia , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Núcleo Celular/metabolismo , Mapeamento Cromossômico , Perfilação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Transportadores de Nitrato , Fenótipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/citologia , Raízes de Plantas/genética , Raízes de Plantas/fisiologiaRESUMO
Liver ischemia-reperfusion (I/R) injury occurs through induction of oxidative stress and release of damage-associated molecular patterns (DAMPs), including cytosolic DNA released from dysfunctional mitochondria or from the nucleus. Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a cytosolic DNA sensor known to trigger stimulator of interferon genes (STING) and downstream type 1 interferon (IFN-I) pathways, which are pivotal innate immune system responses to pathogen. However, little is known about the role of cGAS/STING in liver I/R injury. We subjected C57BL/6 (WT), cGAS knockout (cGAS-/-), and STING-deficient (STINGgt/gt) mice to warm liver I/R injury and that found cGAS-/- mice had significantly increased liver injury compared with WT or STINGgt/gt mice, suggesting a protective effect of cGAS independent of STING. Liver I/R upregulated cGAS in vivo and also in vitro in hepatocytes subjected to anoxia/reoxygenation (A/R). We confirmed a previously published finding that hepatocytes do not express STING under normoxic conditions or after A/R. Hepatocytes and liver from cGAS-/- mice had increased cell death and reduced induction of autophagy under hypoxic conditions as well as increased apoptosis. Protection could be restored in cGAS-/- hepatocytes by overexpression of cGAS or by pretreatment of mice with autophagy inducer rapamycin. Our findings indicate a novel protective role for cGAS in the regulation of autophagy during liver I/R injury that occurs independently of STING. NEW & NOTEWORTHY Our studies are the first to document the important role of cGAS in the acute setting of sterile injury induced by I/R. Specifically, we provide evidence that cGAS protects liver from I/R injury in a STING-independent manner.
Assuntos
Autofagia/fisiologia , Interferon Tipo I , Fígado , Nucleotídeos Cíclicos/metabolismo , Nucleotidiltransferases/metabolismo , Traumatismo por Reperfusão , Animais , Apoptose/fisiologia , DNA Nucleotidiltransferases/fisiologia , Indutores de Interferon/metabolismo , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Fígado/irrigação sanguínea , Fígado/metabolismo , Fígado/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Substâncias Protetoras/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Transdução de SinaisRESUMO
BACKGROUND: There have been no studies to systematically evaluate the two display (3D vs. 2D) systems regarding both laparoscopic and thoracoscopic surgeries in clinical settings; thus, we conducted one to evaluate the safety and efficacy of different visualization systems (two-dimensional and three-dimensional) during endoscopic surgery (laparoscopy or thoracoscopy) in clinical settings. METHODS: A comprehensive search of online databases was performed. Perioperative outcomes were synthesized. Cumulative meta-analysis was performed to evaluate the temporal trend of pooled outcomes. Specific subgroups (laparoscopy vs. thoracoscopy, prospective vs. retrospective study, malignant vs. benign diseases) were examined. Meta-regression was conducted to explore the source of heterogeneity. RESULTS: Twenty-three articles were considered in this analysis, of which 7 were thoracoscopic and 16 were laparoscopic surgeries. A total of 2930 patients were recorded, of which 1367 underwent 3D video-assisted surgery and 1563 underwent 2D display. Overall, significantly shorter operating time (SMD -0.69; p = <0.001), less blood loss (SMD -0.26; p = 0.028) and shorter hospital stays (SMD -0.16; p = 0.016) were found in the 3D display group. Meanwhile, the perioperative morbidity (OR 0.92; p = 0.487), retrieved lymph nodes (SMD 0.09; p = 0.081), drainage duration (SMD -0.15; p = 0.105) and drainage volume (SMD 0.00; p = 0.994) were similar between the two groups. Comparison of the overall outcomes in each subset showed consistency in all groups. CONCLUSIONS: This up-to-date meta-analysis reveals that the 3D display system is superior to the 2D system in clinical settings with significantly shorter operating time, less blood loss and shorter hospital stay. These findings suggest that, in laparoscopic or thoracoscopic surgeries, 3D endoscopic system is preferable when condition permits. Future efforts should be made on decreasing the side effects of 3D display and increasing its cost-effectiveness.
Assuntos
Imageamento Tridimensional/métodos , Cirurgia Vídeoassistida/métodos , Adulto , Idoso , Feminino , Humanos , Laparoscopia/métodos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Toracoscopia/métodosRESUMO
Unfolded protein response (UPR) and endoplasmic reticulum (ER)-phagy are essential for cell homeostasis. Quantum dots (QDs), which have been widely used for biomedical applications, can accumulate in the kidney tissues and may cause renal dysfunction. However, the molecular mechanism of QDs-induced nephrotoxicity is still obscure. The present study was aimed to elucidate the role and mechanism of UPR and ER-phagy in QDs-induced nephrotoxicity. Herein, human embyronic kidney (HEK) cells were exposed to 15, 30, 45, and 60 nM cadmium telluride (CdTe)-QDs for 12 and 24 h. And CdTe-QDs (30-60 nM) inhibited the HEK cell viability. The clathrin-dependent endocytosis was determined as the main pathway of CdTe-QDs cellular uptake. Within cells, CdTe-QDs disrupted ER ultrastructure and induced UPR and FAM134B-dependent ER-phagy. Blocking UPR with inhibitors or siRNA rescued the FAM134B-dependent ER-phagy, which was triggered by CdTe-QDs. Moreover, suppression of UPR or FAM134B-dependent ER-phagy restored the cell vability. In vivo, mice were intravenously injected with 8 and 16 nmol/kg body weight CdTe-QDs for 24 h. Kidney was shown as one of highest distributed organs of CdTe-QDs, resulting in renal dysfunction, as well as UPR and FAM134B-dependent ER-phagy in it. Thus, for the first time, we demonstrated that ER-phagy can be triggered by nanomaterials both in vitro and in vivo. In addition, blocking of UPR and ER-phagy showed protective effects against CdTe-QDs-induced toxicity in kideny cells. Notably, a secreted alkaline phosphatase reporter gene system has been developed as a sensitive and rapid method for evaluating the ER quality under the exposure of nanomaterials.
Assuntos
Compostos de Cádmio/toxicidade , Endocitose , Retículo Endoplasmático/efeitos dos fármacos , Rim/efeitos dos fármacos , Pontos Quânticos/toxicidade , Telúrio/toxicidade , Resposta a Proteínas não Dobradas , Animais , Compostos de Cádmio/administração & dosagem , Linhagem Celular , Retículo Endoplasmático/ultraestrutura , Homeostase , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/metabolismo , Telúrio/administração & dosagemRESUMO
MAIN CONCLUSION: The contribution of variations in coding regions or promoters to the changes in FAE1 expression levels have be quantified and compared in parallel by specifically designed swapping constructs. FATTY ACID ELONGATION1 (FAE1) is a key gene in control of erucic acid synthesis in plant seeds. The expression of FAE1 genes in Brassica oleracea and Capsella rubella, representatives of high and low erucic acid species, respectively, was characterized to provide insight into the regulation of very long-chain fatty-acid biosynthesis in seeds. Virtually, no methylation was detected either in B. oleracea or in C. rubella, suggesting that modification of promoter methylation might not be a predominant mechanism. Swapping constructs were specifically designed to quantify and compare the contribution of variations in coding regions or promoters to the changes in FAE1 expression levels in parallel. A significantly higher fold change in erucic acid content was observed when swapping coding regions rather than when swapping promoters, indicating that the coding region is a major determinant of the catalytic power of ß-ketoacyl-CoA synthase proteins. Common motifs have been proposed as essential for the preservation of basic gene expression patterns, such as seed-specific expression. However, the occurrence of variation in common cis-elements or the presence of species-specific cis-elements might be plausible mechanisms for changes in the expression levels in different organisms. In addition, conflicting observations in previous reports associated with FAE1 expression are discussed, and we suggest that caution should be taken when selecting a plant transformation vector and in interpreting the results obtained from vectors carrying the CaMV 35S promoter.
Assuntos
Acetiltransferases/metabolismo , Brassica/enzimologia , Capsella/enzimologia , Ácidos Erúcicos/metabolismo , Regulação da Expressão Gênica de Plantas , Acetiltransferases/genética , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Brassica/genética , Capsella/genética , Metilação de DNA , Evolução Molecular , Elongases de Ácidos Graxos , Genes Reporter , Motivos de Nucleotídeos , Fases de Leitura Aberta/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Alinhamento de Sequência , Especificidade da EspécieRESUMO
Background: Zinc has been shown to improve intestinal barrier function against Salmonella enterica serovar Typhimurium (S. typhimurium) infection, but the mechanisms involved in this process remain undefined.Objective: We aimed to explore the roles of G protein-coupled receptor (GPR)39 and protein kinase Cζ (PKCζ) in the regulation by zinc of intestinal barrier function.Methods: A Transwell Caco-2 monolayer was pretreated with 0, 50, or 100 µM Zn and then incubated with S. typhimurium for 0-6 h. Afterward, cells silenced by the small interfering RNA for GPR39 or PKCζ were pretreated with 100 µM Zn and incubated with S. typhimurium for 3 h. Finally, transepithelial electrical resistance (TEER), permeability, tight junction (TJ) proteins, and signaling molecules GPR39 and PKCζ were measured.Results: Compared with controls, S. typhimurium decreased TEER by 62.3-96.2% at 4-6 h (P < 0.001), increased (P < 0.001) permeability at 6 h, and downregulated (P < 0.05) TJ protein zonula occludens (ZO)-1 and occludin by 104-123%, as well as Toll-like receptor 2 and PKCζ by 35.1% and 75.2%, respectively. Compared with S. typhimurium-challenged cells, 50 and 100 µM Zn improved TEER by 26.3-60.9% at 4-6 h (P < 0.001) and decreased (P < 0.001) permeability and bacterial invasion at 6 h. A total of 100 µM Zn increased ZO-1, occludin, GPR39, and PKCζ 0.72- to 1.34-fold (P < 0.05); however, 50 µM Zn did not affect ZO-1 or occludin (P > 0.1). Silencing GPR39 decreased (P < 0.05) zinc-activated PKCζ and blocked (P < 0.05) the promotion of zinc on epithelial integrity. Furthermore, silencing PKCζ counteracted the protective effect of zinc on epithelial integrity but did not inhibit GPR39 (P = 0.138).Conclusion: We demonstrated that zinc upregulates PKCζ by activating GPR39 to enhance the abundance of ZO-1, thereby improving epithelial integrity in S. typhimurium-infected Caco-2 cells.
Assuntos
Células Epiteliais/metabolismo , Intestinos/citologia , Proteína Quinase C/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Salmonella typhimurium/fisiologia , Zinco/farmacologia , Células CACO-2 , Suplementos Nutricionais , Células Epiteliais/microbiologia , Regulação Enzimológica da Expressão Gênica , Humanos , Proteína Quinase C/genética , Receptores Acoplados a Proteínas G/genética , Junções Íntimas/fisiologia , Regulação para Cima , Zinco/administração & dosagemRESUMO
OBJECTIVE: To study information gained by Traditional Chinese Medicine (TCM) four diagnostic methods and characteristics of syndrome development before and after treatment in patients with coronary heart disease, and to probe into assessment indexes of therapeutic effects with distinctive TCM features. METHODS: Information from the four diagnostic methods before and after treatment in 100 patients with coronary heart disease was collected using the TCM interrogation scale, a pulse condition instrument, a tongue-face diagnosis instrument, and a voice diagnosis information collection system. Changes in the four diagnostic method results from before and after treatment were analyzed with frequency analysis and t-test methods. RESULTS: Before treatment, deficiency syndrome complicated with hyperactivity of pathogenic factors was most common. After treatment, deficiency syndrome was most common. This change from complex syndromes to single syndromes indicates disease and syndrome alleviation. Frequencies of symptoms gained by interrogation after treatment for syndrome of deficiency of heart-Qi, syndrome of deficiency of heart-Yin, and turbid phlegm syndrome were all less severe than those before treatment. Parameters of face color, color on all sub-regions of tongue, color of tongue fur, septic and greasy fur, and lip color after treatment all had significant changes. After treatment, part of the voice diagnosis parameters in the deficiency of heart-Yin and turbid phlegm syndromes had significant changes, but no significant changes were found in the deficiency of heart-Qi syndrome. CONCLUSION: Use of the TCM four diagnostic methods can provide an effective basis for TCM syndrome diagnosis, observation of development of state of illness, and evaluation of clinical therapeutic effects.
Assuntos
Doença das Coronárias/diagnóstico , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Diagnóstico Diferencial , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Resultado do TratamentoRESUMO
Avian influenza viruses (AIVs) have the potential to cause severe illness in wild birds, domestic poultry, and humans. The ongoing circulation of highly pathogenic avian influenza viruses (HPAIVs) has presented significant challenges to global poultry industry and public health in recent years. This study aimed to elucidate the circulation of HPAIVs during 2019 to 2023. Specifically, we assess the alarming global spread and continuous evolution of HPAIVs. Moreover, we discuss their transmission and prevention strategies to provide valuable references for future prevention and control measures against AIVs.
RESUMO
Liver ischemia-reperfusion injury (LIRI) commonly occurs in liver resection, liver transplantation, shock, and other hemorrhagic conditions, resulting in profound local and systemic effects via associated inflammatory responses and hepatic cell death. Hepatocyte death is a significant component of LIRI and its mechanism was previously thought to be limited to apoptosis and necrosis. With the discovery of novel types of programmed cell death (PCD), necroptosis, ferroptosis, pyroptosis, autophagy, NETosis, and parthanatos have been shown to be involved in LIRI. Understanding the mechanisms underlying cell death following LIRI is indispensable to mitigating the widespread effects of LIRI. Here, we review the roles of different PCD and discuss potential therapy in LIRI.