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1.
PLoS One ; 19(2): e0297756, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38363777

RESUMO

This paper employs low-field nuclear magnetic resonance (LF-NMR) technology to meticulously analyze and explore the intricate soybean infiltration process. The methodology involves immersing soybeans in distilled water, with periodic implementation of Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence experiments conducted at intervals of 20 to 30 minutes to determine the relaxation time T2. Currently, magnetic resonance imaging (MRI) is conducted every 30 minutes. The analysis uncovers the existence of three distinct water phases during the soybean infiltration process: bound water denoted as T21, sub-bound water represented by T22, and free water indicated as T23. The evolution of these phases unfolds as follows: bound water T21 displays a steady oscillation within the timeframe of 0 to 400 minutes; sub-bound water T22 and free water T23 exhibit a progressive pattern characterized by a rise-stable-rise trajectory. Upon scrutinizing the magnetic resonance images, it is discerned that the soybean infiltration commences at a gradual pace from the seed umbilicus. The employment of LF-NMR technology contributes significantly by affording an expeditious, non-destructive, and dynamic vantage point to observe the intricate motion of water migration during soybean infiltration. This dynamic insight into the movement of water elucidates the intricate mass transfer pathway within the soybean-water system, thus furnishing a robust scientific foundation for the optimization of processing techniques.


Assuntos
Glycine max , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Água/química , Movimento (Física)
2.
J Endocrinol ; 259(1)2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37417397

RESUMO

Acute lung injury (ALI) is associated with an increased incidence of respiratory diseases, which are devastating clinical disorders with high global mortality and morbidity. Evidence confirms that fibroblast growth factors (FGFs) play key roles in mediating ALI. Mice were treated with LPS (lipopolysaccharide: 5 mg/kg, intratracheally) to establish an in vivo ALI model. Human lung epithelial BEAS-2B cells cultured in a corresponding medium with LPS were used to mimic the ALI model in vitro. In this study, we characterized FGF10 pretreatment (5 mg/kg, intratracheally) which improved LPS-induced ALI, including histopathological changes, and reduced pulmonary edema. At the cellular level, FGF10 pretreatment (10 ng/mL) alleviated LPS-induced ALI accompanied by reduced reactive oxygen species (ROS) accumulation and inflammatory responses, such as IL-1ß, IL-6, and IL-10, as well as suppressed excessive autophagy. Additionally, immunoblotting and co-immunoprecipitation showed that FGF10 activated nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway via Nrf2 nuclear translocation by promoting the interaction between p62 and keap1, thereby preventing LPS-induced ALI. Nrf2 knockout significantly reversed these protective effects of FGF10. Together, FGF10 protects against LPS-induced ALI by restraining autophagy via p62-Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 signaling pathway, implying that FGF10 could be a novel therapy for ALI.


Assuntos
Lesão Pulmonar Aguda , Fator 2 Relacionado a NF-E2 , Camundongos , Humanos , Animais , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 10 de Crescimento de Fibroblastos/genética , Fator 10 de Crescimento de Fibroblastos/farmacologia , Fator 10 de Crescimento de Fibroblastos/metabolismo , Lipopolissacarídeos/toxicidade , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Autofagia , Pulmão/metabolismo , Pulmão/patologia
3.
BMC Ophthalmol ; 23(1): 196, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37142972

RESUMO

BACKGROUND: To evaluate the feasibility of and identify problems in treating complex rhegmatogenous retinal detachment using foldable capsular buckle scleral buckling. METHODS: This prospective clinical study enrolled five patients with complex rhegmatogenous retinal detachment treated with foldable capsular buckle scleral buckling at the 988th Hospital of People's Liberation Army Joint Logistic Force, China. During the 24-week follow-up period, the patients underwent measurements of their best-corrected visual acuity, slit-lamp examination, indirect ophthalmoscopy, and visual field testing. Additionally, B-ultrasound and fundus photography of the patients' retinal reattachments helped evaluate the treatment's post-surgery efficacy. We determined the safety of foldable capsular buckle scleral buckling based on infection, eye pain, diplopia, elevated intraocular pressure, and other postoperative severe complications. RESULTS: All five patients' complex rhegmatogenous retinal detachments were successfully treated and evaluated via B-ultrasound and fundus photography after surgery. Visual acuity was enhanced in four patients 24 weeks after surgery, while the remaining patients developed diplopia after surgery. No other complications were observed. CONCLUSION: This pilot study preliminarily determined that foldable capsular buckle scleral buckling is feasible for efficient and safe treatment of complex rhegmatogenous retinal detachment. These results support this surgery as a potential and novel alternative to current extraocular procedures for treating complex rhegmatogenous retinal detachment. TRIAL REGISTRATION: The prospective observational clinical study protocol was approved by the Institutional Review Board and Ethics Committee and registered at the clinical research center in the 988th Hospital of People's Liberation Army Joint Logistic Force, China (9,882,019,000).


Assuntos
Descolamento Retiniano , Humanos , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/cirurgia , Descolamento Retiniano/etiologia , Recurvamento da Esclera/efeitos adversos , Projetos Piloto , Diplopia/cirurgia , Estudos Prospectivos , Vitrectomia/métodos , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , Estudos Retrospectivos
4.
J Biomol Struct Dyn ; 41(16): 7665-7676, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36129018

RESUMO

The BA.1 × AY.4 recombinant variant (Deltacron) continues to inflict chaos globally due to its rapid transmission and infectivity. To decipher the mechanism of pathogenesis by the BA.1 × AY.4 recombinant variant (Deltacron), a protein coupling, protein structural graphs (PSG), residue communication and all atoms simulation protocols were used. We observed that the bonding network is altered by this variant; engaging new residues that helps to robustly bind. HADDOCK docking score for the wild type has been previously reported to be -111.8 ± 1.5 kcal/mol while the docking score for the Deltacron variant was calculated to be -128.3 ± 2.5 kcal/mol. The protein structural graphs revealed variations in the hub residues, number of nodes, inter and intra residues communities, and path communication perturbation caused by the acquired mutations in the Deltacron-RBD thus alter the binding approach and infectivity. Moreover, the dynamic behaviour reported a highly flexible structure with enhanced residues flexibility particularly by the loops required for interaction with ACE2. It was observed that these mutations have altered the secondary structure of the RBD mostly transited to the loops thus acquired higher flexible dynamics than the native structure during the simulation. The total binding free energy for each of these complexes, that is, WT-RBD and Deltacron-RBD were reported to be -61.38 kcal/mol and -70.47 kcal/mol. Protein's motion revealed a high trace value in the Deltacron variant that clearly depict more structural flexibility. The broad range of phase space covered by the Deltacron variant along PC1 and PC2 suggests that these mutations are important in contributing conformational heterogeneity or flexibility that consequently help the variant to bind more efficiently than the wild type. The current study provides a basis for structure-based drug designing against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

5.
Molecules ; 27(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36364143

RESUMO

The emergence of immune-evading variants of SARS-CoV-2 further aggravated the ongoing pandemic. Despite the deployments of various vaccines, the acquired mutations are capable of escaping both natural and vaccine-induced immune responses. Therefore, further investigation is needed to design a decisive pharmacological treatment that could efficiently block the entry of this virus into cells. Hence, the current study used structure-based methods to target the RBD of the recombinant variant (Deltacron) of SARS-CoV-2, which was used as a model variant. From the virtual drug screenings of various databases, a total of four hits were identified as potential lead molecules. Key residues were blocked by these molecules with favorable structural dynamic features. The binding free energies further validated the potentials of these molecules. The TBE for MNP was calculated to be -32.86 ± 0.10 kcal/mol, for SANC00222 the TBE was -23.41 ± 0.15 kcal/mol, for Liriodenine the TBE was -34.29 ± 0.07 kcal/mol, while for Carviolin the TBE was calculated to be -27.67 ± 0.12 kcal/mol. Moreover, each complex demonstrated distinct internal motion and a free energy profile, indicating a different strategy for the interaction with and inhibition of the RBD. In conclusion, the current study demands further in vivo and in vitro validation for the possible usage of these compounds as potential drugs against SARS-CoV-2 and its variants.


Assuntos
Tratamento Farmacológico da COVID-19 , Vacinas Virais , Humanos , SARS-CoV-2 , Pandemias , Ligação Proteica , Simulação de Acoplamento Molecular
6.
Artigo em Inglês | MEDLINE | ID: mdl-36065264

RESUMO

Acute lung injury (ALI) is a life-threatening lung change, and 40% of ALI cases result from sepsis. However, the effective treatment for sepsis-induced ALI is limited. It is urgent to explore novel therapeutic targets for ALI caused by sepsis. Anti-inflammatory therapy is a potential effective treatment for sepsis-induced ALI. Toll-like/Interleukin-1 receptor regulator (TILRR) could trigger aberrant inflammatory responses. Nevertheless, the role of TILRR in sepsis-induced ALI remains unknown. Besides, the phosphatidylinositol 3'kinase/protein kinase B (PI3K/Akt) pathway exerts protective effect on sepsis-induced ALI. Thus, the primary aim of the current study was to investigate whether TILRR contributed to sepsis-induced ALI by the PI3K/Akt pathway. To construct the sepsis-induced ALI model, human pulmonary microvascular endothelial cells (HPMVECs) were treated with lipopolysaccharide (LPS). Besides, the mRNA levels and protein levels were determined by quantitative reverse transcription-PCR (qPCR) and Western blot (WB), respectively. Moreover, cell proliferation was identified by the Cell Counting Kit-8 (CCK-8) assay and Annexin V was utilized to detect apoptosis. Furthermore, levels of proinflammatory cytokines and oxidative stress were tested by the enzyme-linked immunosorbent assay (ELISA) while reactive oxygen species (ROS) was determined by the flow cytometer. Results indicated that TILRR was upregulated to suppress the proliferation and induce apoptosis of HPMVECs under LPS treatment. Besides, TILRR induced aberrant inflammatory responses and oxidative stress in HPMVECs under LPS treatment. Mechanistically, TILRR regulated proliferation, apoptosis, inflammatory responses, and oxidative stress in LPS-treated HPMVECs through inactivating the PI3K/Akt pathway. In summary, TILRR aggravated sepsis-induced ALI by suppressing the PI3K/Akt pathway. These results could provide novel therapy targets for sepsis-induced ALI.

7.
J Clin Transl Hepatol ; 10(2): 230-237, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35528974

RESUMO

Background and Aims: We compared lung function parameters in nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD), and examined the association between lung function parameters and fibrosis severity in MAFLD. Methods: In this cross-sectional study, we randomly recruited 2,543 middle-aged individuals from 25 communities across four cities in China during 2016 and 2020. All participants received a health check-up including measurement of anthropometric parameters, biochemical variables, liver ultrasonography, and spirometry. The severity of liver disease was assessed by the fibrosis (FIB)-4 score. Results: The prevalence of MAFLD was 20.4% (n=519) and that of NAFLD was 18.4% (n=469). After adjusting for age, sex, adiposity measures, smoking status, and significant alcohol intake, subjects with MAFLD had a significantly lower predicted forced vital capacity (FVC, 88.27±17.60% vs. 90.82±16.85%, p<0.05) and lower 1 s forced expiratory volume (FEV1, 79.89±17.34 vs. 83.02±16.66%, p<0.05) than those with NAFLD. MAFLD with an increased FIB-4 score was significantly associated with decreased lung function. For each 1-point increase in FIB-4, FVC was diminished by 0.507 (95% CI: -0.840, -0.173, p=0.003), and FEV1 was diminished by 0.439 (95% CI: -0.739, -0.140, p=0.004). The results remained unchanged when the statistical analyses was performed separately for men and women. Conclusions: MAFLD was significantly associated with a greater impairment of lung function parameters than NAFLD.

8.
Technol Health Care ; 30(S1): 105-114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35124588

RESUMO

BACKGROUND: The results of urine tests are often affected by improper midstream urine collection time, urine spilling, and urine pollution, all of which can lead to an increase in the test error. OBJECTIVE: To solve this problem, aiming at improving the toilet environment at the hospitals and public physical examination centers, this paper designs an automatic urine collection system. It can automatically adjust the position of the urine cup with an infrared remote controller, or manually, adjust the position of the urine cup in special situations according to the needs of the user. It also has an alarm function. METHODS: The overall size and shape are designed based on the squatting pan, suitable for disposable plastic urine cups of different shapes and sizes. It can realize the automatic collection of midstream urine, manual collection in exceptional cases, emergency stops, and rescue calls. RESULTS: Through the trial survey, there was a significant difference between the statistical results of using the device and not using the device (t= 13.937, P= 0.000). 96% of the subjects thought that the design of the system was reasonable, 22% thought that it was inconvenient to use, and 91.7% of the medical staff thought that the system met the sampling requirements. CONCLUSIONS: Therefore, the trial evaluation is satisfactory, and the proposed collection system is suitable for use in hospitals at all levels and public health examination centers with a large amount of inspection.


Assuntos
Líquidos Corporais , Coleta de Urina , Hospitais , Humanos , Manejo de Espécimes/métodos , Inquéritos e Questionários , Coleta de Urina/métodos
9.
Technol Health Care ; 30(S1): 469-480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35124621

RESUMO

BACKGROUND: Spatial disorientation (SD) is a problem that pilots often encounter during a flight. One reason for this problem is that among the three types of SD, there is no validated method to detect the Type I (unrecognized) SD. OBJECTIVE: In this pursuit, initially we reviewed the problems and the evaluation methods of associated with SD. Subsequently, we discussed the advantages and disadvantages of the subjective questionnaire evaluation method and the behavior evaluation method. METHODS: On the basis of these analyses, we proposed a method to detect the unrecognized SD that improved the assessment of SD to a significant extent. We developed a new direction to study the unrecognized SD based on the subjective report and the center of pressure (CoP). RESULTS: The proposed evaluation method can assist the pilots to understand the feelings and physical changes, when exposed to unrecognized SD. CONCLUSION: We hope that this evaluation method can provide a strong support in developing a countermeasure against the unrecognized SD and fundamentally solve the severe flight accidents arising due to them.


Assuntos
Militares , Pilotos , Confusão/diagnóstico , Humanos , Orientação Espacial , Inquéritos e Questionários
11.
Bioprocess Biosyst Eng ; 44(9): 1865-1874, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33871701

RESUMO

The flow velocity plays an important role in the growth and characteristics of biofilm in the bioreactor as well as its treatment efficiency, which has been a hot research topic. In a sewage treatment bioreactor, the type of flow is usually turbulence. According to the methods of Reynolds decomposition, the flow velocity of turbulence consists of the time-mean velocity and fluctuation velocity, which usually exist simultaneously in real flow. However, the current research on the influence of turbulence flow velocity mainly focuses on the time-mean velocity, while the fluctuation velocity has not been reported because of very difficult to control. To this end, in this paper, a laboratory oscillating-grid turbulence (OGT) bioreactor with zero time-mean velocity and only fluctuation velocity was designed. In this bioreactor, the fluctuation velocity could be easily manipulated by varying the operational parameters of the grid. Based on the numerical simulation of Gas-liquid two-phase flow, the distributions of fluctuation velocity and corresponding turbulence fluctuation intensity, gas holdup, and Reynolds stress were obtained. After that, the effects of the turbulent fluctuation intensity on the biofilm thickness, density, and composition of extracellular polymeric substances (EPS) were studied experimentally. The results showed that turbulent fluctuation had a significant effect on the physical and chemical properties of biofilms, and the fluctuation velocity promoted the increase in the biofilm density and the content of protein and carbohydrates in EPS. This study was intended to provide theoretical support for the design and operation optimization of bioreactors.


Assuntos
Biofilmes/crescimento & desenvolvimento , Reatores Biológicos , Simulação por Computador , Modelos Biológicos , Esgotos/microbiologia , Purificação da Água
12.
Eur J Pharmacol ; 891: 173730, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33188742

RESUMO

Our research group has previously synthesized various chalcone analogues. Of these analogues, compound 39 has been shown to exhibit potent antioxidative activities but its anti-inflammatory and anti-apoptosis effects remain unclear. Thus, the present study investigated the in vivo and in vitro effects and mechanisms of compound 39 in lipopolysaccharide (LPS)-induced acute lung injury (ALI). To induce ALI, the mice received LPS via a tracheal instillation 6 h after intragastric administration of compound 39 or vehicle. Histological changes, the lung wet/dry weight ratio, and the amounts of protein and inflammatory cells in the broncho-alveolar lavage (BAL) fluid were assessed after 24 h. Additionally, to determine its underlying mechanisms, Western blot and immunofluorescence analyses were used. Moreover, the in vitro effects of compound 39 were also investigated. In the in vivo experiment, compound 39 markedly alleviated histopathological alterations, lung edema, and protein leakage, and exhibited potent anti-inflammatory effects. In the in vitro experiments, compound 39 dose-dependently reduced the levels of pro-inflammatory cytokines and reactive oxygen species. The results suggested that the anti-inflammatory effects of compound 39 were due to suppression of the mitogen-activated protein kinase (MAPK)/nuclear factor κB (NF-κB) pathway. Compound 39 also enhanced the protein levels of Bcl-2 and reduced the protein levels of Bax and cleaved caspase-3. The present study confirmed the anti-inflammatory, oxy-radical prohibitive, and anti-apoptosis activities of compound 39 against LPS-induced tissue and cell damage, and revealed the mechanisms underlying those processes.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Chalconas/farmacologia , Pulmão/efeitos dos fármacos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/síntese química , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Chalconas/síntese química , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Edema Pulmonar/metabolismo , Edema Pulmonar/patologia , Edema Pulmonar/prevenção & controle , Transdução de Sinais
14.
Braz J Med Biol Res ; 53(8): e9501, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578720

RESUMO

Sepsis often leads to cardiac dysfunction and inflammation. This study investigated the clinical value of microRNA-328 (miR-328) in sepsis and its role in cardiac dysfunction and inflammation caused by sepsis. The expression level of miR-328 in the serum of the subjects was detected by qRT-PCR. Receiver operating characteristic (ROC) curve measured the diagnostic value of miR-328 in sepsis. Rat sepsis model was established to detect left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal rate of increase/decrease of left ventricular pressure (±dp/dtmax). Myocardial injury markers serum cardiac troponin I (cTnI), myocardial kinase isoenzyme (CK-MB), and inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). miR-328 expression was assessed in serum of sepsis patients and in rat models of sepsis. The AUC of ROC curve was 0.926, sensitivity 87.60%, and specificity 86.36%. Compared with the sham group, LVSP and +dp/dtmax were decreased in the rat model of sepsis. LVEDP, -dp/dtmax, cTnI, CK-MB, tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß were upregulated in the rat model of sepsis. The low expression of miR-328 reversed these indicators. miR-328 is a diagnostic marker for patients with sepsis, and decreasing the expression level of miR-328 can ameliorate cardiac dysfunction and cardiac inflammation in sepsis.


Assuntos
Cardiopatias , MicroRNAs , Sepse , Animais , Feminino , Humanos , Masculino , Miocárdio , Ratos , Ratos Sprague-Dawley
15.
Retina ; 40(10): 1918-1928, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31725525

RESUMO

PURPOSE: To evaluate the efficacy and primary safety of treating rhegmatogenous retinal detachment (RRD) using foldable capsular vitreous body scleral buckling. METHODS: Five patients with simple RRD were treated with foldable capsular vitreous body scleral buckling. B-ultrasound and fundus photography examining of retina reattachment were used to evaluate the postsurgery efficacy. The safety of the treatment was evaluated based on the occurrence of infection, eye pain, diplopia, elevated intraocular pressure, and other serious postoperative complications after surgery. The observation time after the operation was at least 12 weeks. RESULTS: The simple RRD of all five patients was successfully reattached before being evaluating by B-ultrasound and fundus photography after surgery. Visual acuity was enhanced in two patients who were macularly affected. One patient had temporary diplopia and eye movement limitation after surgery. No other complications were recorded. CONCLUSION: This pilot study determined that foldable capsular vitreous body scleral buckling can be efficacious and safe for simple RRD. The results indicate that this surgery may be a novel alternative to the current extraocular procedures for simple RRD.


Assuntos
Oclusão com Balão , Descolamento Retiniano/cirurgia , Recurvamento da Esclera/métodos , Elastômeros de Silicone , Adulto , Feminino , Humanos , Pressão Intraocular/fisiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Descolamento Retiniano/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia , Acuidade Visual/fisiologia
16.
Braz. j. med. biol. res ; 53(8): e9501, 2020. tab, graf
Artigo em Inglês | LILACS, Coleciona SUS | ID: biblio-1132544

RESUMO

Sepsis often leads to cardiac dysfunction and inflammation. This study investigated the clinical value of microRNA-328 (miR-328) in sepsis and its role in cardiac dysfunction and inflammation caused by sepsis. The expression level of miR-328 in the serum of the subjects was detected by qRT-PCR. Receiver operating characteristic (ROC) curve measured the diagnostic value of miR-328 in sepsis. Rat sepsis model was established to detect left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal rate of increase/decrease of left ventricular pressure (±dp/dtmax). Myocardial injury markers serum cardiac troponin I (cTnI), myocardial kinase isoenzyme (CK-MB), and inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). miR-328 expression was assessed in serum of sepsis patients and in rat models of sepsis. The AUC of ROC curve was 0.926, sensitivity 87.60%, and specificity 86.36%. Compared with the sham group, LVSP and +dp/dtmax were decreased in the rat model of sepsis. LVEDP, -dp/dtmax, cTnI, CK-MB, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β were upregulated in the rat model of sepsis. The low expression of miR-328 reversed these indicators. miR-328 is a diagnostic marker for patients with sepsis, and decreasing the expression level of miR-328 can ameliorate cardiac dysfunction and cardiac inflammation in sepsis.


Assuntos
Humanos , Animais , Masculino , Feminino , Ratos , Sepse , MicroRNAs , Cardiopatias , Ratos Sprague-Dawley , Miocárdio
17.
Nat Cell Biol ; 21(8): 940-951, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31358971

RESUMO

The receptor-interacting serine/threonine-protein kinases RIPK1 and RIPK3 play important roles in necroptosis that are closely linked to the inflammatory response. Although the activation of necroptosis is well characterized, the mechanism that tunes down necroptosis is largely unknown. Here we find that Parkin (also known as PARK2), an E3 ubiquitin ligase implicated in Parkinson's disease and as a tumour suppressor, regulates necroptosis and inflammation by regulating necrosome formation. Parkin prevents the formation of the RIPK1-RIPK3 complex by promoting polyubiquitination of RIPK3. Parkin is phosphorylated and activated by the cellular energy sensor AMP-activated protein kinase (AMPK). Parkin deficiency potentiates the RIPK1-RIPK3 interaction, RIPK3 phosphorylation and necroptosis. Parkin deficiency enhances inflammation and inflammation-associated tumorigenesis. These findings demonstrate that the AMPK-Parkin axis negatively regulates necroptosis by inhibiting RIPK1-RIPK3 complex formation; this regulation may serve as an important mechanism to fine-tune necroptosis and inflammation.


Assuntos
Apoptose/fisiologia , Transformação Celular Neoplásica/genética , Necrose/fisiopatologia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Carcinogênese/genética , Inflamação/metabolismo , Camundongos Knockout , Fosforilação/fisiologia , Ubiquitinação/fisiologia
18.
Water Sci Technol ; 79(1): 73-83, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30816864

RESUMO

The choice of the spatial submodel of a water resource recovery facility (WRRF) model should be one of the primary concerns in WRRF modelling. However, currently used mechanistic models are limited by an over-simplified representation of local conditions. This is illustrated by the general difficulties in calibrating the latest N2O models and the large variability in parameter values reported in the literature. The use of compartmental model (CM) developed on the basis of accurate hydrodynamic studies using computational fluid dynamics (CFD) can take into account local conditions and recirculation patterns in the activated sludge tanks that are important with respect to the modelling objective. The conventional tanks in series (TIS) configuration does not allow this. The aim of the present work is to compare the capabilities of two model layouts (CM and TIS) in defining a realistic domain of parameter values representing the same full-scale plant. A model performance evaluation method is proposed to identify the good operational domain of each parameter in the two layouts. Already when evaluating for steady state, the CM was found to provide better defined parameter ranges than TIS. Dynamic simulations further confirmed the CM's capability to work in a more realistic parameter domain, avoiding unnecessary calibration to compensate for flaws in the spatial submodel.


Assuntos
Hidrodinâmica , Modelos Químicos , Dióxido de Nitrogênio/análise , Esgotos , Eliminação de Resíduos Líquidos/métodos , Abastecimento de Água/estatística & dados numéricos , Conservação dos Recursos Hídricos/métodos , Eliminação de Resíduos Líquidos/estatística & dados numéricos , Recursos Hídricos
19.
Exp Ther Med ; 16(6): 5059-5066, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30542460

RESUMO

Clinical efficacy of metoprolol combined with irbesartan and hydrochlorothiazide and non-invasive ventilator in the emergency treatment of patients with severe heart failure (HF) was investigated. A retrospective analysis of the medical records of 124 patients with severe HF admitted to Binzhou Medical University Hospital from May 2012 to August 2016 was performed. Among them, 78 patients who were treated with metoprolol combined with irbesartan and hydrochlorothiazide and non-invasive ventilator for emergency treatment were enrolled into the Research Group, while the Control Group consisted of 46 patients treated with routine medical treatment. Echocardiographic parameters, 6-minute walking test results, the efficacy of the emergency treatment, cardiac function grading, left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) levels were compared between the two groups. After the emergency treatment, the echocardiographic indexes of both groups increased to different extents (P<0.05). Compared with the results before, patients of both groups walked longer within six minutes after the emergency treatment (P<0.05). After the emergency treatment, the BNP expression levels in the two groups decreased to different degrees (P<0.05). After a 7-day emergency treatment, the efficiency rate of treatment of the Research Group was higher than that of the Control Group (P<0.05). The method is helpful for the recovery of respiratory function, for relieving symptoms in short time, improving cardiac function and promising high safety, using metoprolol and irbesartan and hydrochlorothiazide combined with non-invasive ventilator had satisfactory clinical efficacy in the emergency treatment of patients with severe heart failure and is thus worthy of clinical promotion.

20.
Front Genet ; 9: 556, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532765

RESUMO

Ischemia-reperfusion (I/R) is a common cause of acute kidney injury (AKI), which is associated with high mortality and poor outcomes. Autophagy plays important roles in the homeostasis of renal tubular cells (RTCs) and is implicated in the pathogenesis of AKI, although its role in the process is complex and controversial. Fibroblast growth factor 10 (FGF10), a multifunctional FGF family member, was reported to exert protective effect against cerebral ischemia injury and myocardial damage. Whether FGF10 has similar beneficial effect, and if so whether autophagy is associated with the potential protective activity against AKI has not been investigated. Herein, we report that FGF10 treatment improved renal function and histological integrity in a rat model of renal I/R injury. We observed that FGF10 efficiently reduced I/R-induced elevation in blood urea nitrogen, serum creatinine as well as apoptosis induction of RTCs. Interestingly, autophagy activation following I/R was suppressed by FGF10 treatment based on the immunohistochemistry staining and immunoblot analyses of LC3, Beclin-1 and SQSTM1/p62. Moreover, combined treatment of FGF10 with Rapamycin partially reversed the renoprotective effect of FGF10 suggesting the involvement of mTOR pathway in the process. Interestingly, FGF10 also inhibited the release of HMGB1 from the nucleus to the extracellular domain and regulated the expression of inflammatory cytokines such as TNF-α, IL-1ß and IL-6. Together, these results indicate that FGF10 could alleviate kidney I/R injury by suppressing excessive autophagy and inhibiting inflammatory response and may therefore have the potential to be used for the prevention and perhaps treatment of I/R-associated AKI.

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