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1.
BMC Med ; 22(1): 220, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816882

RESUMO

BACKGROUND: The patterns of blood pressure (BP) change throughout the pregnancy were related to adverse birth outcomes. However, little is known about the long-term effect of BP change patterns on child neurodevelopment. This study aimed to explore the relationship between the BP trajectory and BP variability during pregnancy and early childhood neurodevelopment. METHOD: A total of 2797 mother-newborn pairs were derived from the Wuhan Healthy Baby Cohort Study. BP was measured during each antenatal visit, and Mental and Psychomotor Development Indexes (MDI and PDI) were assessed using the Bayley Scales of Infant Development (BSID) when the children were 2 years old. Delayed neurodevelopment was defined as scores of PDI or MDI less than - 1SD relative to the mean score of the study population. A group-based multi-trajectory model was adopted to identify multi-trajectories of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Visit-to-visit BP variability was assessed by the coefficient of variation (CV), standard deviation (SD), and average real variability (ARV). Generalized linear models and multivariate logistic regressions were used to assess the associations of BP trajectories and variability with BSID scores and delayed neurodevelopment, respectively. RESULTS: Five distinct trajectories for SBP and DBP were identified, namely, "Low-increasing," "Low-stable," "Moderate-decreasing," "Moderate-increasing," and "High-stable" groups. Compared with the "Low-stable" group, the children whose mothers' BP fell into the other four groups had lower PDI scores, and mothers in the "Low-increasing," "Moderate-increasing," and "Moderate-decreasing" groups had 43% (OR: 1.43, 95% CI: 1.01, 2.03), 48% (OR: 1.48, 95% CI: 1.05, 2.08) and 45% (OR:1.45, 95% CI: 1.03, 2.04) higher risk of having offspring with delayed psychomotor neurodevelopment, respectively. High DBP variability was associated with lower BSID scores, and delayed psychomotor neurodevelopment (OR = 1.46, 95% CI: 1.10, 1.92 for DBP-SD; OR = 1.53, 95% CI: 1.16, 2.02 for DBP-CV). CONCLUSION: Our findings suggest that BP change patterns assessed by multi-trajectory and visit-to-visit variability were associated with lower BSID scores and delayed neurodevelopment. Health professionals should be aware of the influence of BP level and its oscillations during pregnancy on the risk of delayed neurodevelopment.


Assuntos
Pressão Sanguínea , Desenvolvimento Infantil , Humanos , Feminino , Pressão Sanguínea/fisiologia , Gravidez , Pré-Escolar , Desenvolvimento Infantil/fisiologia , Masculino , Adulto , Recém-Nascido , Lactente , Estudos de Coortes , Efeitos Tardios da Exposição Pré-Natal
2.
J Immunol ; 208(2): 321-327, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34911771

RESUMO

Previous studies have demonstrated that 8-hydroxydeoxyguanosine (8-OHdG) exerted key roles in various pulmonary diseases, but the evidence for its role in community-acquired pneumonia (CAP) was lacking. The goal of this research was to evaluate the correlations of serum 8-OHdG with the severity and prognosis among patients with CAP through a prospective cohort study. A total of 239 patients with CAP and 239 healthy participants were enrolled. Fasting blood samples were collected. 8-OHdG and inflammatory cytokines were measured by ELISA. On admission, serum 8-OHdG was significantly increased in patients with CAP compared with control subjects. Besides, serum 8-OHdG was incrementally increased in line with CAP severity scores. Pearson correlative analysis found that serum 8-OHdG was correlated with clinical characteristics and inflammatory cytokines in patients with CAP. Linear and logistic regression analysis showed that serum 8-OHdG was positively associated with CAP severity scores. Furthermore, the prognostic outcomes were tracked. Higher serum 8-OHdG on admission increased the risks for intensive care unit admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stay among patients with CAP. Serum 8-OHdG combination with confusion, respiratory rate, blood pressure, and age ≥65 y or pneumonia severity index had stronger predictive powers for death than single 8-OHdG, CAP severity scores, or several inflammatory cytokines in patients with CAP. These results indicated that serum 8-OHdG is positively associated with the severity and poor prognosis in patients with CAP, demonstrating that 8-OHdG may be involved in the pathophysiology process of CAP.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/sangue , Infecções Comunitárias Adquiridas/patologia , Pneumonia/sangue , Pneumonia/mortalidade , Índice de Gravidade de Doença , Idoso , Biomarcadores/sangue , Infecções Comunitárias Adquiridas/sangue , Cuidados Críticos/estatística & dados numéricos , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Pneumonia/patologia , Prognóstico , Estudos Prospectivos , Respiração Artificial/estatística & dados numéricos
3.
Anal Chem ; 95(4): 2303-2311, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36655772

RESUMO

Sensitive and reliable clustered regularly interspaced short palindromic repeats (CRISPR) quantification without preamplification of the sample remains a challenge. Herein, we report a CRISPR Cas12a-powered silicon surface-enhanced Raman spectroscopy (SERS) ratiometric chip for sensitive and reliable quantification. As a proof-of-concept application, we select the platelet-derived growth factor-BB (PDGF-BB) as the target. We first develop a microfluidic synthetic strategy to prepare homogeneous silicon SERS substrates, in which uniform silver nanoparticles (AgNPs) are in situ grown on a silicon wafer (AgNPs@Si) by microfluidic galvanic deposition reactions. Next, one 5'-SH-3'-ROX-labeled single-stranded DNA (ssDNA) is modified on AgNPs via Ag-S bonds. In our design, such ssDNA has two fragments: one fragment hybridizes to its complementary DNA (5'-Cy3-labeled ssDNA) to form double-stranded DNA (dsDNA) and the other fragment labeled with 6'-carboxy-X-rhodmine (ROX) extends out as a substrate for Cas12a. The cleavage of the ROX-tagged fragment by Cas12a is controlled by the presence or not of PDGF-BB. Meanwhile, Cy3 molecules serving as internal standard molecules still stay at the end of the rigid dsDNA, and their signals remain constant. Thereby, the ratio of ROX signal intensity to Cy3 intensity can be employed for the reliable quantification of PDGF-BB concentration. The developed chip features an ultrahigh sensitivity (e.g., the limit of detection is as low as 3.2 pM, approximately 50 times more sensitive than the fluorescence counterpart) and good reproducibility (e.g., the relative standard deviation is less than 5%) in the detection of PDGF-BB.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Nanopartículas Metálicas/química , Sistemas CRISPR-Cas/genética , Silício/química , Análise Espectral Raman/métodos , Becaplermina , Reprodutibilidade dos Testes , Prata/química , DNA/química , DNA de Cadeia Simples
4.
Anal Chem ; 94(14): 5699-5706, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35344343

RESUMO

Metal-organic frameworks (MOFs) are promising as novel disinfectants due to the reactive oxygen species (ROS) produced in their photocatalytic processes. The optimal MOF is screened as the best disinfectant, representing high-efficacy production of ROS under photocatalytic conditions. However, current methods to screen abundant MOFs for disinfectant application are generally semiquantitative or ex situ methods [such as electron paramagnetic resonance (EPR) measurements], so achieving a strategy that can quantitatively screen an optimal MOF in situ and is reliable is demanded. Herein, we developed a three-dimensional (3D) shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) platform to study the dynamic photocatalytic processes of various MOFs (e.g., ZIF-67, ZIF-8, and UIO-66) in situ. This platform comprises silica shell-isolated gold nanoparticles (AuNPs) modified on silicon nanowire arrays (SiNWArs). The MOF is then self-assembled on the 3D-SHINERS substrate. Using this platform, we recorded dynamic spectroscopic evidence of ROS formation by various MOFs under sunlight irradiation. By dynamic comparison, ZIF-67 has the most robust photocatalytic efficiency, ∼1.7-fold stronger than that of ZIF-8 and ∼42.6-fold stronger than that of UIO-66. As expected, ZIF-67 displays the best antibacterial ability, up to 99% in the agar plate assay. This work provides a versatile platform for dynamically monitoring photocatalytic performance and screening antibacterial MOFs.


Assuntos
Desinfetantes , Nanopartículas Metálicas , Estruturas Metalorgânicas , Antibacterianos/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , Ácidos Ftálicos , Espécies Reativas de Oxigênio , Análise Espectral Raman
5.
Environ Toxicol ; 37(1): 151-160, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34652871

RESUMO

BACKGROUND: Cadmium is a ubiquitous toxic heavy metal and environmental toxicant. Inflammation exerts central roles in the process of chronic obstructive pulmonary disease (COPD). However, few epidemiological studies on the correlation between cadmium exposure and COPD are available. The aim of this study was to evaluate the correlations among serum cadmium, inflammatory cytokines and pulmonary function in COPD patients. METHODS: All 940 COPD patients were finally recruited in this study. Demographic characteristics and clinical information were extracted. Fasting serum was collected. Serum cadmium was detected through graphite furnace atomic absorption spectrophotometry. Serum inflammatory cytokines were measured using enzyme-linked immunosorbent assay. RESULTS: All patients were classified into three groups according to the tertile division of serum cadmium concentration: low (<0.77 µg/L, L), medium (0.77-1.01 µg/L, M), and high (1.01 µg/L, H). Logistic regression analysis found that serum cadmium was inversely correlated with pulmonary function before and after adjusted confounding variables. When stratified by gender, serum cadmium was still negatively correlated with pulmonary function in COPD patients. Moreover, higher serum cadmium elevated CAT (COPD Assessment Test) score before and after adjusted confounding variables. Though a non-linear association between serum cadmium and inflammatory cytokines, serum cadmium was positively associated with inflammatory cytokines (TNF-α and MCP-1). TNF-α and MCP-1 exerted a partial mediator in the association between cadmium exposure and pulmonary function decline in COPD patients. CONCLUSIONS: Serum cadmium concentration is inversely correlated with pulmonary function among COPD patients. Inflammatory cytokines may be important mediators for cadmium-induced pulmonary function decline in COPD patients.


Assuntos
Citocinas , Doença Pulmonar Obstrutiva Crônica , Cádmio , Estudos de Casos e Controles , Humanos , Pulmão , Fator de Necrose Tumoral alfa
6.
BMC Pulm Med ; 21(1): 393, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34856971

RESUMO

BACKGROUND: Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study. METHODS: All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II. RESULTS: Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively. CONCLUSIONS: Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.


Assuntos
Infecções Comunitárias Adquiridas/sangue , Interleucina-17/sangue , Pneumonia/sangue , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença
7.
Nat Mater ; 18(6): 627-637, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31114073

RESUMO

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/ß-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.


Assuntos
Proteínas de Homeodomínio/metabolismo , Tecido Parenquimatoso/fisiologia , Dente/citologia , Dente/embriologia , Adolescente , Animais , Feminino , Proteínas de Homeodomínio/genética , Humanos , Incisivo/citologia , Incisivo/embriologia , Camundongos Endogâmicos , Dente Serotino/citologia , Técnicas de Cultura de Órgãos , Tecido Parenquimatoso/citologia , Gravidez , Regiões Promotoras Genéticas , Regeneração , Células Estromais/fisiologia , Suínos , Fator A de Crescimento do Endotélio Vascular/genética , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismo
8.
Med Sci Monit ; 23: 5599-5612, 2017 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-29172017

RESUMO

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by excessive fat accumulation in the form of triglycerides. The incidence of NAFLD and hyperlipidemia, with their associated risks of end-stage liver and cardiovascular diseases, is increasing rapidly. This study aimed to investigate the effects of scutellarin on the experimental NAFLD in high-fat diet fed and chronic stress rats, and its possible mechanism. MATERIAL AND METHODS Sprague-Dawley rats were fed with high-fat diet and subjected to chronic stress for 12 weeks, and administered orally with scutellarin for 4 weeks (n=8), and then blood and livers were harvested for analyzing. Enzyme activity assay, immunofluorescence, Western blot, and quantitative RT-PCR were performed to analyze the factors of the oxidant/antioxidant system and pathway. RESULTS After the high-fat diet and chronic stress administration for 12 weeks, serum and liver lipid metabolism of treatment groups with the different doses of SCU effectively improved and the degree of oxidative damage reduced. Using Western blot assay and immunofluorescence (IF) staining assay, Nrf2, HO-1, and PI3K, and AKT proteins significantly increased after SCU treatment for 4 weeks (P<0.01). The hepatic mRNA expression of HO-1, NQO1, and Nrf2 in SCU treatment groups was upregulated significantly through quantitative RT-PCR assay (P<0.05). However, compared to the positive control group, no difference was detected in the SCU (100 or 300 mg/kg) groups (P>0.05). These results indicate that SCU protects against NAFLD in rats via attenuation of oxidative stress. CONCLUSIONS The antioxidant effects of SCU on NAFLD are possibly dependent on PI3K/AKT activation with subsequent Nrf2 nuclear translocation, which increases expression of HO-1 and NQO1. We therefore suggest that breviscapine may be a potentially useful therapeutic strategy for NAFLD and hyperlipidemia.


Assuntos
Apigenina/metabolismo , Glucuronatos/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Animais , Antioxidantes/farmacologia , Apigenina/farmacologia , Dieta Hiperlipídica , Glucuronatos/farmacologia , Hiperlipidemias/prevenção & controle , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Triglicerídeos
9.
Am J Med Sci ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825074

RESUMO

BACKGROUND: Superoxide dismutase 1 (SOD1) is one of the most important participants of antioxidant enzyme system in biological system. Previous studies have found that SOD1 is associated with many inflammatory diseases. The goal of this study was to assess the associations of serum SOD1 with the severity and prognosis in community-acquired pneumonia (CAP) patients by a prospective cohort study. METHODS: CAP patients were enrolled from the Second Affiliated Hospital of Anhui Medical University. Peripheral blood samples were gathered. The level of serum SOD1 was detected through enzyme linked immunosorbent assay (ELISA). Clinical characteristics and demographic information were analyzed. RESULTS: The level of serum SOD1 was gradually upregulated with elevated CAP severity scores. Spearman correlation coefficient or Pearson rank correlation analyses indicated that serum SOD1 was strongly connected with many clinical parameters among CAP patients. Further linear and logistic regression analyses found that the level of serum SOD1 was positively associated with CRB-65, CURB-65, SMART-COP, and CURXO scores among CAP patients. Moreover, serum higher SOD1 at admission substantially increased the risks of ICU admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stays during hospitalization. Serum SOD1 level combination with CAP severity scores elevated the predictive abilities for severity and death compared with alone serum SOD1 and CAP severity scores in CAP patients during hospitalization. CONCLUSION: The level of serum SOD1 is positively associated with the severity and poor prognosis in CAP patients, suggesting that SOD1 is implicated in the initiation and progression of CAP. Serum SOD1 may be regarded as a biomarker to appraise the severity and prognosis for CAP patients.

10.
Synth Syst Biotechnol ; 8(4): 606-609, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37753197

RESUMO

Adoptive transfer of T cells engineered with chimeric antigen receptor (CAR) has been proved to have robust anti-tumor effects against hematological malignancies. However, problems about safety and efficacy, such as cytokine release syndrome (CRS), T cell exhaustion and antigen escape are still raised when patients are treated with CAR-T cells. Moreover, CAR-T therapy has limited applications in treating solid tumors, owing to inefficient infiltration and poor functional persistence of CAR-T cells and diverse immunosuppression in tumor microenvironment. In order to overcome these limitations and broad its applications, multiple controllable CAR-T technologies were exploited. In this article, we review the designs of intelligent controlled CAR-T technologies and the innovations that they bring about in recent years.

11.
Toxics ; 11(7)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37505599

RESUMO

With their unique geographical characteristics, semi-closed narrow bays are important places for human survival but vulnerable to pollution. Because pollutants (polycyclic aromatic hydrocarbons, PAHs) migrate and undergo transformation through a dynamic mechanism in bays of this type, environmental authorities have formulated a series of effective measures for pollution prevention and control, but these are difficult to realize. Based on monitoring and historical data, a multiphase-coupled hydrodynamic model combined with a carcinogenic risk-assessment model was able to solve the challenging environmental problem. Results showed that the hydrodynamic condition in the semi-closed narrow bay was very complex. A weaker hydrodynamic force had an adverse influence on the diffusion of pollutants, further amplified in part by the head of the semi-closed narrow bay, resulting in a higher ecological risk. The prediction results indicated that the total amount of PAHs transported from seawater to sediments was about 4.7 × 1013 ng/year, which might cause serious threats to aquaculture or human health.

12.
Mar Pollut Bull ; 193: 115201, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37385180

RESUMO

Dredged material ocean dumping activities are likely an important source of microplastics (MPs) in coastal areas but have received little attention globally. In this study, we investigated the spatiotemporal distribution and characteristics of MPs in sediments at eight dredged material dumping sites of China. MPs were separated from sediment through density flotation, and polymer types were identified using µ-FTIR. The results showed that the average MP abundance was 112.82 ± 109.68 items/kg d.w. The MPs were more abundant at nearshore dumping sites than at distant dumping sites. Dumping activities may be the main contributor of MPs to Site BD1, the farthest dumping site from shore, but only a minor source of MPs at the other dumping sites. The characteristics of MPs were dominated by transparent PET fibers <1 mm. Overall, sediments at the dumping sites exhibited relatively low to moderate concentrations of MPs in comparison to most other coastal sediments.


Assuntos
Microplásticos , Poluentes Químicos da Água , Plásticos , Sedimentos Geológicos , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , China , Oceanos e Mares
13.
Respir Investig ; 61(1): 84-94, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36336629

RESUMO

BACKGROUND: Survivin is a member of apoptosis inhibitor proteins that evokes cellular proliferation and inhibits apoptosis. However, the role of survivin in community-acquired pneumonia (CAP) patients remains to be firmly established. The aim of this cohort study was to evaluate the correlations of serum survivin with the severity and prognosis of CAP patients. METHODS: This research included 470 eligible CAP patients. Serum fasting samples were drawn from patients, and serum survivin was measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, demographic characteristics and clinical information were collected. The prognosis of CAP patients was tracked. RESULTS: Serum survivin gradually decreased with elevated CAP severity scores. Additionally, the correlative analysis suggested that serum survivin was associated with many clinical characteristics. Furthermore, mixed linear and logistic regression models indicated that serum survivin was negatively associated with severity. After adjusting for confounding factors, logistic regression analyses found that lower serum survivin on admission elevated the risks of mechanical ventilation, vasoactive agent usage, longer hospital stays, ICU admission, and even death during hospitalization. Serum survivin in combination with CAP severity scores elevated the predictive capacities for severity and death in CAP patients compared with a single indicator. CONCLUSION: On admission, there are inverse dose-response associations of serum survivin with severity and poor prognosis in CAP patients, demonstrating that serum survivin may be involved in the pathophysiology process of CAP. Serum survivin may serve as a potential biomarker for disease evaluation and prognosis in CAP patients.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Humanos , Estudos de Coortes , Survivina , Pneumonia/diagnóstico , Prognóstico , Biomarcadores , Índice de Gravidade de Doença
14.
Int J Biol Sci ; 19(4): 1192-1210, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923942

RESUMO

Cisplatin is widely recommended in combination for the treatment of tumors, thus inevitably increasing the incidence of cisplatin-induced acute kidney injury. Mitophagy is a type of mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. Ferroptosis, a new modality of programmed cell death, is characterized by iron-dependent phospholipid peroxidation and oxidative membrane damage. However, the role of mitophagy in ferroptosis in kidney disease is unclear. Here, we investigated the mechanism underlying both BNIP3-mediated and PINK1-PARK2-mediated mitophagy-induced attenuation of ferroptosis in cisplatin-induced acute kidney injury. The results showed that cisplatin induced mitochondrial injury, ROS release, intracellular iron accumulation, lipid peroxidation and ferroptosis in the kidney, which were aggravated in Bnip3 knockout, Pink1 knockout or Park2 knockout cisplatin-treated mice. Ferrstatin-1, a synthetic antioxidative ferroptosis inhibitor, rescued iron accumulation, lipid peroxidation and ferroptosis caused by inhibition of mitophagy. Thus, the present study elucidated a novel mechanism by which both BNIP3-mediated and PINK1-PARK2-mediated mitophagy protects against cisplatin-induced renal tubular epithelial cell ferroptosis through the ROS/HO1/GPX4 axis.


Assuntos
Injúria Renal Aguda , Ferroptose , Camundongos , Animais , Cisplatino/efeitos adversos , Mitofagia/genética , Espécies Reativas de Oxigênio/metabolismo , Células Epiteliais/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Camundongos Knockout , Proteínas Quinases/metabolismo
15.
Zhongguo Zhong Yao Za Zhi ; 37(11): 1629-33, 2012 Jun.
Artigo em Zh | MEDLINE | ID: mdl-22993996

RESUMO

OBJECTIVE: To study on the method for establishing the Qi stagnation and blood stasis rat model and analyze the affecting factors. METHOD: The orthogonal design was adopted to study the influences of joint stimulations including noise, light, electricity, ice water bath, tail-clamping on model rats. The 'flying spot' method was used to dynamically simulate blood flow velocity in microcirculation. the pressure sensing technology of MOTO was adopted to detect hemorheology-related indicators. And the coagulation method was used to detect blood coagulation-related indicators. RESULT: Compared with the negative control group, all model groups showed significant reduction in the blood flow velocity in mesenteric microcirculation and increase in the whole blood viscosity at high, medium and low shear rate, the plasma viscosity and the fibrinogen content in four blood coagulation indicators. CONCLUSION: Noise, light, electricity, tail-clamping, bondage and icewater-bath make significant impact on model rats.


Assuntos
Circulação Sanguínea , Modelos Animais , Animais , Comportamento Animal/fisiologia , Feminino , Masculino , Microcirculação/fisiologia , Fenótipo , Ratos , Ratos Wistar
16.
Front Surg ; 9: 902710, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034347

RESUMO

Background: The T classification of non-small-cell lung cancer (NSCLC) was upgraded from T1 to T2 when accompanied by visceral pleural invasion (VPI). However, the association between VPI and prognostic outcomes was obscure in NSCLC patients with ≤3 cm tumor size (TS), which leaded the controversy of selection of T classification. The goal was to evaluate the effect of VPI on the prognosis of NSCLC with ≤ 3cm TS and present a modified T classification. Methods: A total of 14,934 NSCLC patients without distant metastasis were recruited through a retrospective study in the SEER database. The effect of VPI on lung cancer specific survival (LCSS) was evaluated using survival curve and COX regression analysis in NSCLC patients with ≤3 cm TS. Results: Although there was no difference of the LCSS of PL0 and PL1 patients with ≤2 cm TS in patients without lymph node (LN) metastasis, the LCSS was lower in PL2 patients than those in PL0 (T1a: p < 0.001; T1b: p = 0.001). Moreover, the LCSS was decreased in PL1 and PL2 patients with 2-3 cm TS compared with PL0 (T1c: PL1, p < 0.001; PL2, p = 0.009) of patients without LN metastasis. No difference of LCSS was observed in patients with LN metastasis between PL0 with PL1 and PL2. Conclusion: In NSCLC patients without LN metastasis and TS ≤ 2 cm, tumor with PL1 should remain defined as T1, tumor with PL2 should be defined as T2. However, 2-3 cm TS patients with PL1 or PL2 should both defined as T2. Meanwhile, ≤3 cm TS patients with LN metastasis can be regarded as T1, whether NSCLC patients accompanied with PL1 or PL2.

17.
Front Med (Lausanne) ; 9: 1071864, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36755884

RESUMO

Ferroptosis is a new type of cell death caused by the lack of glutathione peroxidase 4 (GPX4) and the imbalance of cellular redox. It is characterized by the accumulation of lipid peroxides on cell membranes. Multiple regulatory pathways of ferroptosis include the GPX4, glutamate-cystine antiporter (System Xc-), lipid metabolism, and iron metabolism pathways. Recent studies have reported that autophagy-dependent ferroptosis (ferroptosis meditated by ferritinophagy, lipophagy, and clockophagy) plays a significant role in the occurrence of several diseases, including diseases affecting the nerves, liver, lungs, and kidneys. This review provides an overview of research progress made on autophagy-dependent ferroptosis in kidney diseases.

18.
Nat Commun ; 13(1): 1255, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35273187

RESUMO

Currently optical-based techniques for in vivo microbial population imaging are limited by low imaging depth and highly light-scattering tissue; and moreover, are generally effective against only one specific group of bacteria. Here, we introduce an imaging and therapy strategy, in which different bacteria actively eat the glucose polymer (GP)-modified gold nanoparticles through ATP-binding cassette (ABC) transporter pathway, followed by laser irradiation-mediated aggregation in the bacterial cells. As a result, the aggregates display ~15.2-fold enhancement in photoacoustic signals and ~3.0-fold enhancement in antibacterial rate compared with non-aggregated counterparts. Significantly, the developed strategy allows ultrasensitive imaging of bacteria in vivo as low ~105 colony-forming unit (CFU), which is around two orders of magnitude lower than most optical contrast agents. We further demonstrate the developed strategy enables the detection of ~107 CFU bacteria residing within tumour or gut. This technique enables visualization and treatment of diverse bacteria, setting the crucial step forward the study of microbial ecosystem.


Assuntos
Ouro , Nanopartículas Metálicas , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias , Ecossistema , Ouro/química , Nanopartículas Metálicas/química
19.
Front Med (Lausanne) ; 9: 798343, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783645

RESUMO

Background: Four-hydroxynonenal (4-HNE) exerts a central role in the pathophysiological process of pulmonary diseases. The aim of this project was to evaluate the correlations between serum 4-HNE with severity and prognosis in patients with community-acquired pneumonia (CAP) by a prospective cohort study. Materials and Methods: A total of 239 patients with CAP and healthy volunteers were recruited. Fasting blood was collected. Serum 4-HNE was measured with ELISA. Clinical characteristics and demographic information were obtained. The relationships between serum 4-HNE and clinical characteristics were evaluated through the Spearman or Pearson correlation coefficient. The associations of serum 4-HNE with severity and prognosis were estimated through logistic regression analysis. Results: On admission, serum 4-HNE was upregulated in patients with CAP compared with healthy volunteers. Serum 4-HNE was gradually increased in line with CAP scores. Additionally, elderly patients with CAP were more prone to suffer from 4-HNE elevation. Moreover, serum 4-HNE was positively correlated with CAP severity scores. Meanwhile, the poor prognostic outcomes were tracked among patients with CAP. Higher serum 4-HNE on admission increased the risks of mechanical ventilation, vasoactive agent usage, and death in patients with CAP during hospitalization. The predictive powers for severity and death were increased in serum 4-HNE compared with CAP severity scores and inflammatory cytokines. Conclusion: Serum 4-HNE on admission is positively correlated with the severity and poor prognosis among patients with CAP, indicating that 4-HNE participates in the pathophysiology of CAP. Serum 4-HNE may be used as an earlier biomarker for diagnosis and prognosis in patients with CAP.

20.
Animals (Basel) ; 12(12)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35739815

RESUMO

The rapid decline of longfin smelt Spirinchus thaleichthys, a threatened euryhaline forage fish in California, is a serious concern for scientists and resource managers. To recover and conserve this species, a captive culture program was initiated, focusing on the collection, captive rearing and breeding of wild broodstock, and the rearing of their offspring. Although progress has been made in the collection of broodstock and the production and culturing of larvae, no studies have evaluated the rearing of juvenile life stages in captivity. The present study examines methodological considerations for culturing F1 juvenile longfin smelt, specifically, the first efforts toward weaning juveniles to a dry commercial pellet feed. Cultured juvenile longfin smelt were fed live Artemia only or co-fed Artemia and dry feed for 62 days, and the effects of feed type on juvenile survival, growth, body condition, and fatty acid profiles were examined. No significant differences were observed between feeding treatments, despite an 80% reduction in Artemia in the co-feeding treatment. Furthermore, examination of fish stomach contents at the end of the trial confirmed the transition to dry feed. This is the first study to indicate successful feeding by longfin smelt on dry commercial pellets, and suggests that juvenile longfin smelt can be fully weaned onto dry feeds. Results of this study are critical for closing the lifecycle of longfin smelt in captivity and developing a successful conservation culture program for this imperiled species.

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