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2.
Plant Commun ; 5(1): 100670, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-37563835

RESUMO

Grain number, one of the major determinants of yield in Triticeae crops, is largely determined by spikelet number and spike rachis node number (SRN). Here, we identified three quantitative trait loci (QTLs) for SRN using 145 recombinant inbred lines derived from a barley R90/1815D cross. qSRN1, the major-effect QTL, was mapped to chromosome 2H and explained up to 38.77% of SRN variation. Map-based cloning revealed that qSRN1 encodes the RAWUL domain-containing protein HvSRN1. Further analysis revealed that two key SNPs in the HvSRN1 promoter region (∼2 kb upstream of the transcription start site) affect the transcript level of HvSRN1 and contribute to variation in SRN. Similar to its orthologous proteins OsLAX2 and ZmBA2, HvSRN1 showed protein-protein interactions with HvLAX1, suggesting that the LAX2-LAX1 model for spike morphology regulation may be conserved in Poaceae crops. CRISPR-Cas9-induced HvSRN1 mutants showed reduced SRN but increased grain size and weight, demonstrating a trade-off effect. Our results shed light on the role of HvSRN1 variation in regulating the balance between grain number and weight in barley.


Assuntos
Hordeum , Hordeum/genética , Locos de Características Quantitativas/genética , Grão Comestível/genética , Poaceae/genética , Produtos Agrícolas/genética
3.
World J Stem Cells ; 15(7): 654-664, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37545754

RESUMO

Acute pancreatitis (AP) often leads to a high incidence of cardiac injury, posing significant challenges in the treatment of severe AP and contributing to increased mortality rates. Mesenchymal stem cells (MSCs) release bioactive molecules that participate in various inflammatory diseases. Similarly, extracellular vesicles (EVs) secreted by MSCs have garnered extensive attention due to their comparable anti-inflammatory effects to MSCs and their potential to avoid risks associated with cell transplantation. Recently, the therapeutic potential of MSCs-EVs in various inflammatory diseases, including sepsis and AP, has gained increasing recognition. Although preclinical research on the utilization of MSCs-EVs in AP-induced cardiac injury is limited, several studies have demonstrated the positive effects of MSCs-EVs in regulating inflammation and immunity in sepsis-induced cardiac injury and cardiovascular diseases. Furthermore, clinical studies have been conducted on the therapeutic application of MSCs-EVs for some other diseases, wherein the contents of these EVs could be deliberately modified through prior modulation of MSCs. Consequently, we hypothesize that MSCs-EVs hold promise as a potential therapy for AP-induced cardiac injury. This paper aims to discuss this topic. However, additional research is essential to comprehensively elucidate the underlying mechanisms of MSCs-EVs in treating AP-induced cardiac injury, as well as to ascertain their safety and efficacy.

5.
Oncol Rep ; 49(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36382652

RESUMO

Subsequently to the publication of the above article, a concerned reader drew to the Editors' attention that the cell invasion and migration assay data shown in Fig. 3B and D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that these contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 34: 595­602, 2015; DOI: 10.3892/or.2015.4051].

6.
Front Public Health ; 10: 1031529, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466503

RESUMO

Introduction: Early identification of AKI was always considered to improve patients' prognosis. Some studies found that AKI early warning tools didn't affect patients' prognosis. Therefore, additional studies were necessary to explore the reasons. Methods: This study was a secondary analysis of a multicenter randomized controlled trial that found electronic health record warnings for AKI did not influence patients' prognoses. Univariate, multivariate, subgroup, curve fitting, and threshold effect analysis were used to explore the association between AKI warnings detected by attending physicians and the patient's prognosis. Results: A total of 6,030 AKI patients were included in the study. The patients were classified into two groups based on the rate of AKI alerts detected by attending physicians: the partial group (n = 5,377), and the complete group (n = 653). In comparison to the partial group, the complete group significantly decreased 14-day AKI progression, 14-day dialysis, and 14-day mortality, with adjusted ORs of 0.48 (0.33, 0.70), 0.26 (0.09, 0.77), and 0.53 (0.33, 0.84) respectively, and the complete group significantly improve the discharge to home, with an OR value of 1.50 (1.21, 1.87). When the rate of AKI alerts detected by the attending physicians as a continuity variable, we found that the rate of alerts seen by attending physicians was associated with 14-day mortality and the discharge to home, with adjusted ORs of 1.76 (1.11, 2.81) and 1.42 (1.13, 1.80). The sensitivity analysis, curve-fitting analysis, and threshold effect analysis also showed that the rate of alert seen by the attending physician was correlated with the patient's prognosis. Conclusion: The rate of AKI alert detection by attending physician were related to the patient's prognosis. The higher the rate of AKI alert detection by attending physicians, the better the prognosis of patients with AKI.


Assuntos
Injúria Renal Aguda , Médicos , Humanos , Injúria Renal Aguda/diagnóstico , Pessoal de Saúde , Prognóstico
7.
Dis Markers ; 2022: 3117805, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092959

RESUMO

Objective: This study was to evaluate the efficacy of antimicrobial step-down therapy versus conventional antimicrobial therapy in the treatment of patients with sepsis. Methods: Between September 2020 and September 2021, 65 patients with sepsis treated in the intensive care unit (ICU) of our hospital were recruited and assigned at a ratio of 1 : 1 to receive either conventional antimicrobial therapy (sulbactam plus cefoperazone) (control group) or antimicrobial step-down therapy (imipenem/cilastatin) (observation group). The results of drug sensitivity tests and clinical effects were evaluated comprehensively after 3-5 d of treatment, downgraded, and upgraded, or maintenance treatment was administered for 10 d. Outcome measures included clinical and laboratory indices and treatment efficacy. Results: Antimicrobial step-down therapy resulted in a significantly higher efficacy and lower levels of white blood cell (WBC) count and C-reactive protein (CRP) versus conventional antimicrobial therapy (P < 0.05). The patients given antimicrobial step-down therapy showed a significantly shorter duration of antimicrobial drug administration, temperature recovery, time of respiratory support, and ICU stays versus conventional antimicrobial therapy (P < 0.05). Conclusion: Antimicrobial step-down therapy contributes to the mitigation of inflammatory responses in patients with sepsis and shortens the duration of antimicrobial drug use and ICU stay versus conventional antimicrobial therapy. The reliability of the conclusions can be further increased if multicenter and large sample clinical observations can be conducted, which is the direction of endeavor for future clinical studies.


Assuntos
Anti-Infecciosos , Sepse , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Reprodutibilidade dos Testes , Sepse/tratamento farmacológico
8.
Front Cell Dev Biol ; 10: 800925, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35419359

RESUMO

Background: SLC1A5, a ferroptosis regulator gene, plays a dual role in cancer regulation. However, the roles of SLC1A5 in pancreatic adenocarcinoma (PAAD) remain elusive. Methods: SLC1A5's expression and somatic mutation information were determined by TCGA, GEO, Oncomine, and cBioPortal databases. Its prognostic value was assessed in TCGA cohort and was validated in three independent cohorts. The effects of SLC1A5 on the tumor immune microenvironment were analyzed by the CIBERSORT algorithm, ssGSEA method, and TISIDB and TIMER databases. The "oncoPredict" R package, TIDE algorithm, ImmuCellAI online tool, and GSE35141 and GSE59357 datasets were used to ascertain its therapeutic correlations. GSEA and Western blot were applied to reveal the effects of SLC1A5 on the mTORC1 signaling pathway and ferroptosis process. The biofunctions of SLC1A5 were assessed by MTT, wound-healing, Transwell, and xenograft assays. Results: SLC1A5 was significantly upregulated in the PAAD samples but was not commonly accompanied with somatic mutation (2.3%). Overexpression of SLC1A5 led to a poor prognosis and was identified as an independent prognostic factor. Moreover, high SLC1A5 expression suppressed the antitumor immune process by changing the infiltrating levels of immune cells. As for therapeutic correlations, SLC1A5 was related to the efficacy of dasatinib, sunitinib, sorafenib, and imatinib but may not predict that of radiotherapy, chemotherapeutic drugs, and immune checkpoints inhibitors (ICIs). Notably, the overexpression of SLC1A5 could activate the mTORC1 signaling pathway and may increase the cellular sensitivity to ferroptosis. Finally, the overexpression of SLC1A5 markedly promoted proliferation, migration, and invasion of pancreatic cancer cells. At the in vivo level, SLC1A5 deletion inhibited tumor growth in a mice xenograft model. Conclusions: SLC1A5 prefers to play as an accomplice rather than an opponent in PAAD. Our findings provide novel insights into PAAD treatment.

9.
Int J Gen Med ; 15: 4259-4272, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480993

RESUMO

Background: Intensive care unit (ICU) delirium is one of the most common clinical syndromes that results in many adverse events that affect patients, families, and hospitals. To date, there has been no tool for effectively predicting the occurrence of delirium in emergency intensive care unit (EICU) patients. Methods: We conducted a retrospective cohort study and constructed a prediction model for 319 patients in EICU, who met our inclusion criteria. We analyzed the relationship between patients' clinical data within 24 hours of admission and delirium, applied univariate and multivariate logistic regression analyses to select the most relevant variables for construction of nomogram models, then applied bootstrapping for internal validation. Results: A total of five variables, namely stomach and urinary tubes, as well as sedative, mechanical ventilation and APACHE-II scores, were selected for model construction. We generated a total of five sets of models (three sets of construction models and two sets of internal verification models), with similar predictive value. The optimal model was selected, and together with the 5 variables used to construct a nomogram. The AUC of the MFP model in all patients was 0.76 (0.70, 0.82), whereas that in non-elderly patients (<60 years old) for the full model was 0.83 (0.74, 0.91). In elderly patients (≥60 years old), the AUC of the MFP model was 0.82 (0.73, 0.91). Conclusion: Overall, the five-marker-based prognostic tool, established herein, can effectively predict the occurrence of delirium in EICU patients.

10.
Bioengineered ; 13(1): 1717-1735, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35000541

RESUMO

Pyroptosis is an inflammatory programmed cell death, showing potentials to be a novel anti-cancer approach. However, the roles of pyroptosis-related (PR) genes (PRGs) in pancreatic adenocarcinoma (PAAD) remain elusive. In the present study, we constructed a novel PR risk signature through the lasso regression analysis. The risk signature was greatly conducive to PAAD prognostic assessment. PR risk score was identified as an independent prognostic factor and could distinguish the prognostic differences of most clinical subgroups. Meanwhile, it could improve the traditional prognostic models based on TNM-staging. Next, its prognostic value was also tested in five validation cohorts. Using CIBERSORT, ESTIMATE, and ssGSEA algorithms, the effects of PR risk signature on tumor immune microenvironment (TIM) were explored. High PR risk suppressed antitumor immune through decreasing the infiltrating levels of CD8 T and NK cells. The genomic information and histological expression of risk PRGs were uncovered by USCA and HPA databases. Somatic mutation, methylation alteration, and homozygous CNV of eight PRGs barely occurred in PAAD samples. As for therapeutic correlation, PR risk score may not predict the efficacy of PD-1/L1 inhibitors and was weakly associated with multiple drug susceptibilities. Finally, the biofunctions of toll like receptor 3 (TLR3) in pancreatic cancer (PC) cells were investigated through qPCR, MTT, colony formation, and Transwell assays. Overexpression of TLR3 could promote the proliferation, migration, and invasion of PC cells. In conclusion, PRGs play crucial roles in prognosis, progression, and immune microenvironment of PAAD. TLR3 is expected to be a promising therapeutic target.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Neoplasias Pancreáticas/genética , Receptor 3 Toll-Like/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Prognóstico , Piroptose , Análise de Sobrevida , Microambiente Tumoral , Neoplasias Pancreáticas
11.
Cell Cycle ; 21(2): 172-186, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34882521

RESUMO

Circular RNA hsa_circ_0073748 (circ_0073748) is upregulated in patients with acute pancreatitis (AP), a clinically common sudden inflammatory response. MicroRNA (miR)-132-3p is a stress-induced factor with high conservation between species. Herein, expression and role of circ_0073748 and miR-132-3p in caerulein-induced pancreatitis were studied. Expression levels of circ_0073748, miR-132-3p, TNF receptor associated factor 3 (TRAF3), Bcl-2 and Bcl-2-associated X protein (Bax) were examined by reverse transcription-quantitative PCR and Western blotting. Cell proliferation was measured by MTS and EdU assays. Flow cytometry and assay kits detected apoptosis, inflammatory, and oxidative responses. Western blotting detected nuclear factor (NF)-κB signaling pathway. Circ_0073748 was upregulated and miR-132-3p was downregulated in AP patients' plasma and human pancreatic ductal HPDE6-C7 cells with caerulein induction. Interfering circ_0073748 and reinforcing miR-132-3p improved cell viability, EdU incorporation, and superoxide dismutase (SOD) activity of caerulein-treated HPDE6-C7 cells but suppressed malonaldehyde (MDA), IL-6 and TNF-α levels and apoptosis rate. Moreover, TRAF3 downregulation was allied with circ_0073748 silencing and miR-132-3p overexpression in caerulein-induced HPDE6-C7 cells. Mechanically, circ_0073748 was identified as a sponge for miR-132-3p to modulate TRAF3 expression, thus establishing a competitive endogenous RNA (ceRNA) regulation model. Notably, circ_0073748 blockage could suppress expressions of phosphorylated P65 (p-P65) and p-IκB in caerulein-induced HPDE6-C7 cells by promoting miR-132-3p and inhibiting TRAF3. Silencing circ_0073748 and upregulating miR-132-3p could alleviate caerulein-induced HPDE6-C7 injury and inactivate canonical NF-κB signal by inhibiting TRAF3. Circ_0073748/miR-132-3p/TRAF3 ceRNA pathway might be one underlying mechanism and therapeutic target of caerulein-induced AP.


Assuntos
MicroRNAs , Pancreatite , Doença Aguda , Apoptose/genética , Ceruletídeo/metabolismo , Ceruletídeo/toxicidade , Humanos , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Pancreatite/genética , Pancreatite/metabolismo , Fator 3 Associado a Receptor de TNF/genética , Fator 3 Associado a Receptor de TNF/metabolismo
12.
Front Med (Lausanne) ; 8: 753035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778315

RESUMO

Introduction: COVID-19 patients with hypotension and hypoxemia had a significantly worse outcome. The purpose of this research was to ascertain the risk factors affecting the prognoses of these patients and to develop appropriate prognostic prediction tools. Methods: From March 1, 2020, to April 16, 2020, a retrospective cohort analysis of COVID-19 patients with hypotension and hypoxemia was performed. The univariate and multivariate analyses were performed to identify the associated risk factors influencing the prognosis of COVID-19 patients with hypotension and hypoxemia, and the selected variables were then utilized to construct and validate the prediction model for these patients. Results: Three hundred and twenty-seven COVID-19 patients with hypotension and hypoxemia who met the inclusion and exclusion criteria were included in this study. Age, temperature, troponin, and blood glucose were related to mortality in COVID-19 patients with hypotension and hypoxemia in both univariate and multivariate analyses. The MFP model (multiple fractional polynomial model), full model, and stepwise model were utilized to build the prediction model, and their AUCs were, respectively, 0.902 (0.868, 0.936), 0.902 (0.868, 0.936), and 0.902 (0.868, 0.936). Because the sample size for this research was limited, we utilized bootstrapping for internal validation. The AUCs of Bootstrap full and Bootstrap stepwise were 0.902 (0.867, 0.936) and 0.902 (0.868, 0.936), respectively. Conclusion: Age, temperature, troponin, and blood glucose levels were associated with mortality in COVID-19 patients with hypotension and hypoxemia. Additionally, the prediction model developed using the variables above showed a high predictive value for predicting the prognosis of these individuals.

13.
Front Nutr ; 8: 717918, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513902

RESUMO

Introduction: Although low serum albumin (ALB) may worsen acute kidney injury (AKI), additional study is needed to establish the connection between ALB and the prognosis of critically ill patients with AKI and treated with continuous renal replacement therapy (CRRT). Methods:A secondary analysis of a bi-center, retrospective, and observational study, such as critically ill patients with AKI and treated with CRRT from January 2009 to September 2016. The univariate analysis, multi-factor regression analysis, sensitivity analysis, and curve-fitting analysis were applied to explore the association of ALB with the 28 and 90 days mortality of critically ill patients with AKI and treated with CRRT, and the removal efficiency of serum phosphorus. Results: From January 2009 to September 2016, 1,132 cases with AKI and treated with CRRT met the inclusion criteria and enrolled in this study. We found that the higher ALB before CRRT, the lower the 28- and 90-day mortality of patients with AKI and treated with CRRT, the higher removal efficiency of serum phosphorus, the adjusted hazard ratio (HR) value for 28-day mortality in the four models were separately 0.92 (0.90, 0.95), 0.91 (0.89, 0.94), 0.92 (0.89, 0.95), and 0.92 (0.89, 0.95); the adjusted HR value for 90 day mortality in the four models were 0.91 (0.89, 0.94), 0.92 (0.89, 0.95), 0.92 (0.89, 0.95), and 0.92 (0.89, 0.96); the adjusted OR value for the removal efficiency of serum phosphorus in the four models were separately -0.04 (-0.07, -0.01), -0.05 (-0.08, -0.01), -0.04 (-0.08, -0.01), and -0.04 (-0.08, -0.01). The sensitivity analysis and curve-fitting analysis also showed that ALB before CRRT was correlated with the 28 and 90 days mortality of critically ill patients with AKI and treated with CRRT and the removal efficiency of serum phosphorus. Conclusion: The higher the serum ALB before CRRT, the lower the mortality of critically ill patients with AKI and treated with CRRT, and the higher the clearance efficiency of serum phosphorus.

14.
J Cell Mol Med ; 25(19): 9241-9254, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34448533

RESUMO

Acute pancreatitis (AP) is a serious condition carrying a mortality of 25-40%. Extracellular vesicles (EVs) have reported to exert potential functions in cell-to-cell communication in diseases such as pancreatitis. Thus, we aimed at investigating the mechanisms by which EV-encapsulated metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) might mediate the M1 polarization of macrophages in AP. Expression patterns of MALAT1, microRNA-181a-5p (miR-181a-5p) and high-mobility group box 1 protein (HMGB1) in serum of AP patients were determined. EVs were isolated from serum and pancreatic cells. The binding affinity among miR-181a-5p, MALAT1 and HMGB1 was identified. AP cells were co-cultured with EVs from caerulein-treated MPC-83 cells to determine the levels of M1/2 polarization markers and TLR4, NF-κB and IKBa. Finally, AP mouse models were established to study the effects of EV-encapsulated MALAT1 on the M1 polarization of macrophages in AP in vivo. MALAT1 was transferred into MPC-83 cells via EVs, which promoted M1 polarization of macrophages in AP. MALAT1 competitively bound to miR-181a-5p, which targeted HMGB1. Moreover, MALAT1 activated the TLR4 signalling pathway by regulating HMGB1. EV-encapsulated MALAT1 competitively bound to miR-181a-5p to upregulate the levels of IL-6 and TNF-α by regulating HMGB1 via activation of the TLR4 signalling pathway, thereby inducing M1 polarization of macrophages in AP. In vivo experimental results also confirmed that MALAT1 shuttled by EVs promoted M1 polarization of macrophages in AP via the miR-181a-5p/HMGB1/TLR4 axis. Overall, EV-loaded MALAT1 facilitated M1 polarization of macrophages in AP via miR-181a-5p/HMGB1/TLR4, highlighting a potential target for treating AP.


Assuntos
Vesículas Extracelulares/metabolismo , Proteína HMGB1/genética , Macrófagos/imunologia , Macrófagos/metabolismo , MicroRNAs/genética , Pancreatite/etiologia , RNA Longo não Codificante/metabolismo , Adulto , Idoso , Animais , Apoptose/genética , Linhagem Celular Tumoral , Bases de Dados Genéticas , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Inativação Gênica , Humanos , Ativação de Macrófagos , Masculino , Camundongos , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Pancreatite/metabolismo , Pancreatite/patologia , RNA Longo não Codificante/genética , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
15.
Gene ; 795: 145804, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34175402

RESUMO

Ferroptosis, a new form of programmed cell death, provides a new option for anti-tumor treatment. However, the roles of ferroptosis-related (FR) genes in pancreatic adenocarcinoma (PAAD) were not fully elaborated. In the present study, 185 TCGA samples and 81 ICGC samples were used as training and validation cohorts, respectively. A novel FR risk signature (ALOX5, ALOX12, PTGS2, SAT1, STEAP3 and SQLE) was constructed via the Lasso regression analysis. In TCGA cohort, the risk signature was identified as an independent prognostic factor. Decision curve analysis (DCA) indicated that FR risk score could increase the net benefit when making clinical-decision. In addition, we constructed a nomogram to predict the overall survival rate (OSR) of individual at 1,2,3 year. Meanwhile, the prognostic value was partly validated in ICGC cohort. Through immune analyses, we found that high FR risk could affect the immune abundances of five lymphocytes but not effectively affect the activities of immune-related pathways. The expressions of most FR risk genes did not correlate with that of PD-L1(CD274) and CTLA4. Further, through RT-qPCR tests, the expressions of PTGS2 and SQLE were proven to be significantly upregulated in normal pancreatic duct epithelia cell (HPDE6-C7) compared to pancreatic cancer cells (SW1990 and BxPC-3). MTT, wound-healing and transwell assays revealed that silencing PTGS2 and SQLE could inhibit the proliferation, migration and invasion of pancreatic cancer cells. Besides, western-blot assays showed that blocking PTGS2 and SQLE expressions could suppress the protein expressions of cyclin D1 and N-cadherin, but facilitate that of E-cadherin, which suggested that they were involved in the epithelial to mesenchymal transition (EMT). Collectively, FR risk signature provides an important complement for PAAD prognostic analysis. High FR risk level can adversely affect anti-tumor immune process, but may not serve as a predictive marker of ICIs efficacy. PTGS2 and SQLE are proven to possess cancer-promoting abilities in PAAD.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/genética , Ferroptose/genética , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Antígenos CD/genética , Atlas como Assunto , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Biologia Computacional/métodos , Ciclo-Oxigenase 2/genética , Mineração de Dados/métodos , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Humanos , Invasividade Neoplásica , Nomogramas , Ductos Pancreáticos/metabolismo , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Prognóstico , Risco , Esqualeno Mono-Oxigenase/genética , Transcriptoma , Neoplasias Pancreáticas
16.
Inflammation ; 44(4): 1565-1580, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33725236

RESUMO

The purpose of the present study is to investigate the role of CREB in cardiomyocytes proliferation in regulation of HDAC2-dependent TLR4/NF-κB pathway in severe acute pancreatitis (SAP)-induced myocardial injury. The SAP rat model was developed by injecting sodium touracholate into SD rats and then infected with lentivirus vectors expressing sh-CREB in the presence/absence of LPS. The pathological alterations of rat pancreatic and cardiac tissues were observed by HE staining. TUNEL assay was used to study apoptosis of cardiomyocytes. Next, the loss- and gain-function assay was conducted in LPS-induced myocardial injury cardiomyocytes to define the roles of CREB, HDAC2, and TLR4 in cardiomyocyte proliferation, apoptosis, inflammation, and myocardial injury in vitro. ChIP assay was used to study the enrichment of CREB bound to HDAC2 promoter. RT-qPCR and Western blot analysis were used to detect the expressions of related mRNA and proteins in the NF-κB pathway, respectively. CREB was found to be overexpressed in both SAP tissues and cells. CREB directly bound to the promoter of HDAC2 and activated its expression. Overexpressed CREB or HDAC2 inhibited proliferation and promoted apoptosis of cardiomyocytes. Suppression of CREB inhibited the HDAC2/TLR4/NF-κB cascade to promote proliferation and inhibit apoptosis of cardiomyocytes. The in vitro results were validated in vivo experiments. Coherently, suppression of CREB can inhibit HDAC2/TLR4/NF-κB cascade to promote cardiomyocyte proliferation, thus ameliorating SAP-induced myocardial injury.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/antagonistas & inibidores , Histona Desacetilase 2/antagonistas & inibidores , Miócitos Cardíacos/metabolismo , NF-kappa B/antagonistas & inibidores , Pancreatite/metabolismo , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/biossíntese , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Inativação Gênica/fisiologia , Histona Desacetilase 2/biossíntese , Histona Desacetilase 2/genética , Masculino , Miócitos Cardíacos/patologia , NF-kappa B/biossíntese , NF-kappa B/genética , Pancreatite/genética , Pancreatite/prevenção & controle , Gravidade do Paciente , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/biossíntese , Receptor 4 Toll-Like/genética
17.
Cancer Invest ; 39(1): 39-54, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33176521

RESUMO

The specific roles of N6-methyladenosine (m6A) regulatory genes in pancreatic adenocarcinoma (PAAD) have not been fully elucidated. In present study, a novel risk signature was constructed by five m6A-related genes (including METTL3, METTL14, KIAA1429, ALKBH5 and YTHDF1) and was identified as an independent prognostic factor (HR = 13.192) via TCGA (185 samples) databases. The immune abundances of 22 leukocyte subtypes in each PAAD sample were exhibited via the CIBERSORT algorithm. High risk group promoted infiltration levels of Macrophages M0 and M2 cells and decreased that of B cells naive, T cells CD8 and T regulatory cells.


Assuntos
Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica/genética , Metiltransferases/genética , Neoplasias Pancreáticas/genética , Adenocarcinoma/mortalidade , Progressão da Doença , Humanos , Neoplasias Pancreáticas/mortalidade , Prognóstico , Análise de Sobrevida , Microambiente Tumoral
18.
Cell Transplant ; 29: 963689720967672, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33172292

RESUMO

Myocardial infarction (MI) is one of the most serious cardiovascular diseases associated with myocardial ischemia/reperfusion (I/R) injury. Glaucocalyxin A (GLA) is a biologically active ent-kauranoid diterpenoid that has been found to ameliorate myocardial I/R injury in mice. However, the mechanism has not been fully investigated. In the present study, we aimed to investigate the effect of GLA on rat cardiomyocytes H9c2 cells exposed to hypoxia/reoxygenation (H/R). The results showed that GLA treatment improved cell viability of H/R-stimulated H9c2 cells. Administration with GLA suppressed the H/R-stimulated reactive oxygen species (ROS) production in H9c2 cells. GLA also elevated the activities of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase in H/R-stimulated H9c2 cells. Moreover, GLA prevented H/R-stimulated cell apoptosis in H9c2 cells, as evidenced by increased bcl-2 expression, decreased bax expression, as well as reduced caspase-3 activity. Furthermore, GLA enhanced the activation of protein kinase B (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in H9c2 cells exposed to H/R. Additionally, treatment with LY294002 reserved the protective effects of GLA on H/R-stimulated oxidative injury in H9c2 cells. In conclusion, these findings suggested that GLA protected H9c2 cells from H/R-stimulated oxidative damage, which was mediated by the Akt/Nrf2/HO-1 signaling pathway. Thus, GLA might be a promising therapeutic agent for the prevention and treatment of myocardial I/R.


Assuntos
Diterpenos do Tipo Caurano/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Western Blotting , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Heme Oxigenase (Desciclizante)/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
Clin Cardiol ; 43(9): 1024-1031, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32573817

RESUMO

BACKGROUND: Cardiac arrest is still a global public health problem at present. The neurological outcome is the core indicator of the prognosis of cardiac arrest. However, there is no effective means or tools to predict the neurological outcome of patients with coma and survived 24 hours after successful cardiopulmonary resuscitation (CPR). HYPOTHESIS: Therefore, we expect to construct a prediction model to predict the neurological outcome for patients with coma and survived 24 hours after successful CPR. METHODS: A retrospective cohort study was used to construct a prediction model of the neurological function for patients with coma and survived 24 hours after successful CPR. From January 2007 to December 2015, a total of 262 patients met the inclusion and exclusion criteria. RESULTS: The predictive model was developed using preselected variables by a systematic review of the literature. Finally, we get five sets of models (three sets of construction models and two sets of internal verification models) which with similar predictive value. The stepwise model, which including seven variables (age, noncardiac etiology, nonshockable rhythm, bystander CPR, total epinephrine dose, APTT, and SOFA score), was the simplest model, so we choose it as our final predictive model. The area under the ROC curve (AUC), specificity, and sensitivity of the stepwise model were respectively 0.82 (0.77, 0.87), 0.72and 0.82. The AUC, specificity, and sensitivity of the bootstrap stepwise (BS stepwise) model were respectively 0.82 (0.77, 0.87), 0.71, and 0.82. CONCLUSION: This new and validated predictive model may provide individualized estimates of neurological function for patients with coma and survived 24 hours after successful CPR using readily obtained clinical risk factors. External validation studies are required further to demonstrate the model's accuracy in diverse patient populations.


Assuntos
Reanimação Cardiopulmonar , Coma/terapia , Técnicas de Apoio para a Decisão , Parada Cardíaca/terapia , Sistema Nervoso/fisiopatologia , Idoso , Reanimação Cardiopulmonar/efeitos adversos , Coma/diagnóstico , Coma/fisiopatologia , Feminino , Parada Cardíaca/diagnóstico , Parada Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Med Sci Monit ; 26: e920880, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32235819

RESUMO

BACKGROUND Type 2 diabetes mellitus is a global public health problem. Prediabetes may be reversed by weight loss, diet, and lifestyle changes. However, without intervention, between 30-50% of individuals with prediabetes develop type 2 diabetes. This retrospective population study was conducted to develop a predictive model of prediabetes and incident type 2 diabetes mellitus using data from 2004 to 2015 from the DRYAD Japanese hospital database. MATERIAL AND METHODS A retrospective longitudinal population study was conducted using the DRYAD database from Murakami Memorial Hospital, Gifu, Japan, to construct a predictive model for prediabetes and incident type 2 diabetes mellitus in the population. Univariate analysis and multivariate analysis were performed to identify the variables that were associated with prediabetes. These variables were used to construct (75% samples) and verify (25% samples) the predictive model. RESULTS From 2004 to 2015, a total of 11,113 cases were identified. Multivariate logistic regression analysis included the six variables of age, waist circumference, smoking history, the presence of fatty liver, fasting blood glucose (FBG), and glycated hemoglobin (HbA1c) level. Data were used to construct (75% samples) and verify (25% samples) in a predictive model. The area under the receiver operating characteristic (ROC) curve (AUC) of the predictive model was 0.87 (0.85-0.89) in the training cohort and 0.87 (0.86-0.90) in the validation cohort. CONCLUSIONS A prognostic model based on six variables was predictive for incident type 2 diabetes mellitus and prediabetes in a healthy population in Japan.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Nomogramas , Estado Pré-Diabético/diagnóstico , Adulto , Fatores Etários , Glicemia/análise , Índice de Massa Corporal , Bases de Dados Factuais/estatística & dados numéricos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Incidência , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Circunferência da Cintura
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