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1.
Exp Cell Res ; 426(1): 113552, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36914061

RESUMO

It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins. In vivo experiments showed that the ginsenoside Rg1 administration could significantly improve the cognitive function of MCAO rats, and in vitro experimental data showed that ginsenoside Rg1 significantly alleviated neuronal damage via inhibiting the inflammatory response in microglia cells co-cultured under oxygen and glucose deprivation/reoxygenation (OGD/R) condition in gradient dependent. The mechanism study showed that the effect of ginsenoside Rg1 depends on the suppression of TLR4/MyD88/NF-κB and TLR4/TRIF/IRF-3 pathways in microglia cells. In a word, our research shows that ginsenoside Rg1 has great application potential in attenuating the cerebral I/R injury by targeting TLR4 protein in the microglia cells.


Assuntos
Isquemia Encefálica , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Ratos , Animais , Microglia/metabolismo , Receptor 4 Toll-Like/metabolismo , Fármacos Neuroprotetores/farmacologia , Isquemia Encefálica/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
2.
Cell Mol Life Sci ; 80(9): 247, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37578641

RESUMO

Controlled mRNA storage and stability is essential for oocyte meiosis and early embryonic development. However, how to regulate mRNA storage and stability in mammalian oogenesis remains elusive. Here we showed that LSM14B, a component of membraneless compartments including P-body-like granules and mitochondria-associated ribonucleoprotein domain (MARDO) in germ cell, is indispensable for female fertility. To reveal loss of LSM14B disrupted primordial follicle assembly and caused mRNA reduction in non-growing oocytes, which was concomitant with the impaired assembly of P-body-like granules. 10× Genomics single-cell RNA-sequencing and immunostaining were performed. Meanwhile, we conducted RNA-seq analysis of GV-stage oocytes and found that Lsm14b deficiency not only impaired the maternal mRNA accumulation but also disrupted the translation in fully grown oocytes, which was closely associated with dissolution of MARDO components. Moreover, Lsm14b-deficient oocytes reassembled a pronucleus containing decondensed chromatin after extrusion of the first polar body, through compromising the activation of maturation promoting factor, while the defects were restored via WEE1/2 inhibitor. Together, our findings reveal that Lsm14b plays a pivotal role in mammalian oogenesis by specifically controlling of oocyte mRNA storage and stability.


Assuntos
Oócitos , Oogênese , Animais , Feminino , RNA Mensageiro/genética , Oogênese/genética , Folículo Ovariano , Meiose/genética , Fertilidade/genética , Mamíferos
3.
Appl Opt ; 63(4): 1182-1187, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437417

RESUMO

The investigation of atmospheric aerosols holds paramount importance within the environmental realm. This significance arises from the intricate nature of aerosol distribution and size in real-life hazy weather conditions. In this work, we have employed the equivalent radius of the aerosols in haze weather obtained from the volume spectrum, and then the scattering characteristics of these aerosols are obtained using the equivalent radius. Pearson correlation coefficients have been used for revealing a strong correlation by comparing Aeronet website data and simulation results with a minimum value of 0.657.

4.
Plant Foods Hum Nutr ; 79(2): 526-530, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38530542

RESUMO

The antiglycation mechanisms of three structurally different salvianolic acids (Sals) including salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and salvianolic acid C (Sal-C) were investigated using the bovine serum albumin (BSA)-fructose model. The results showed that the three compounds could inhibit the formation of glycation products, maintain protein structural stability, mitigate the development of amyloid fibrils and scavenge radicals. Notably, Sal-A possessed the highest anti-glycated activity compared with Sal-B and Sal-C. This may be related to the fact that Sal-A contained the most molecules of caffeic acid (Sal-A, Sal-B, and Sal-C possessing two, one, and zero caffeic acid units, respectively), and caffeic acid played a leading role in the antiglycation properties relative to Danshensu. Moreover, these compounds quenched the intrinsic fluorescence intensity of BSA in a static mode, with the binding constants in the order of Sal-A > Sal-B > Sal-C. Obviously, Sal-A possessed the strongest binding affinity among these compounds, which may be one of the reasons why it exhibited the optimal antiglycation capability. Furthermore, molecular docking demonstrated that the three Sals exerted protective effects on BSA by preventing glycation modification of lysine and arginine residues. These findings would provide valuable insights into the potential application of Sals for alleviating non-enzymatic glycation of protein.


Assuntos
Benzofuranos , Ácidos Cafeicos , Lactatos , Polifenóis , Soroalbumina Bovina , Soroalbumina Bovina/química , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/química , Glicosilação/efeitos dos fármacos , Polifenóis/farmacologia , Polifenóis/química , Benzofuranos/farmacologia , Benzofuranos/química , Lactatos/farmacologia , Lactatos/química , Alcenos/farmacologia , Alcenos/química , Animais , Produtos Finais de Glicação Avançada/química , Produtos Finais de Glicação Avançada/metabolismo , Bovinos , Simulação de Acoplamento Molecular , Depsídeos
5.
BMC Cancer ; 23(1): 548, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37322417

RESUMO

BACKGROUND: In recent years, multiple coagulation and fibrinolysis (CF) indexes have been reported to be significantly related to the progression and prognosis of some cancers. OBJECTIVE: The purpose of this study was to comprehensively analyze the value of CF parameters in prognosis prediction of pancreatic cancer (PC). METHODS: The preoperative coagulation related data, clinicopathological information, and survival data of patients with pancreatic tumor were collected retrospectively. Mann Whitney U test, Kaplan-Meier analysis, and Cox proportional hazards regression model were applied to analyze the differences of coagulation indexes between benign and malignant tumors, as well as the roles of these indexes in PC prognosis prediction. RESULTS: Compared with benign tumors, the preoperative levels of some traditional coagulation and fibrinolysis (TCF) indexes (such as TT, Fibrinogen, APTT, and D-dimer) were abnormally increased or decreased in patients with pancreatic cancer, as well as Thromboelastography (TEG) parameters (such as R, K, α Angle, MA, and CI). Kaplan Meier survival analysis based on resectable PC patients showed that the overall survival (OS) of patients with elevated α angle, MA, CI, PT, D-dimer, or decreased PDW was markedly shorter than other patients; moreover, patients with lower CI or PT have longer disease-free survival. Further univariate and multivariate analysis revealed that PT, D-dimer, PDW, vascular invasion (VI), and tumor size (TS) were independent risk factors for poor prognosis of PC. According to the results of modeling group and validation group, the nomogram model based on independent risk factors could effectively predict the postoperative survival of PC patients. CONCLUSION: Many abnormal CF parameters were remarkably correlated with PC prognosis, including α Angle, MA, CI, PT, D-dimer, and PDW. Furthermore, only PT, D-dimer, and PDW were independent prognostic indicators for poor prognosis of PC, and the prognosis prediction model based on these indicators was an effective tool to predict the postoperative survival of PC.


Assuntos
Nomogramas , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Prognóstico , Coagulação Sanguínea , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas
6.
Pediatr Res ; 93(3): 715-719, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35681087

RESUMO

BACKGROUND: We analyzed the demographic and clinical characteristics of children with immunoglobulin A (IgA) nephropathy using data in the first pages of electronic health records of 22 hospitals from 2016 to 2018. METHODS: Information collected included gender, age, infection site, etiological infection, acute kidney injury (AKI), and chronic kidney disease (CKD) stages 2-5. We analyzed the gender and age distribution of children with IgA nephropathy, the characteristics of children complicated with AKI and CKD, and the influence of geographical distribution and economic status on the incidence of IgA nephropathy. RESULTS: We included a total of 4006 patients with IgA nephropathy. Incidence in males gradually increased with age. Seventy-nine cases (1.97%) had AKI. We found no significant difference in gender (P = 0.19) or age (P = 0.07) between the AKI and non-AKI groups. Twenty-nine patients had CKD (0.72%), who were significantly older than those in the non-CKD group (P < 0.0001). The incidence of IgA nephropathy in less-developed areas was significantly lower than that in developed areas (P = 0.0002). CONCLUSIONS: The incidence of IgA nephropathy was high mainly in males. Age was an important factor affecting CKD. The disease was related to environment and economic status. IMPACT: We analyze the demographic and clinical characteristics of children with immunoglobulin A (IgA) nephropathy using data in the first pages of electronic health records. This is a large sample, multi-center study. The incidence of IgA nephropathy in males increased gradually with age. Age was an important factor affecting CKD. The disease was related to environment and economic status.


Assuntos
Injúria Renal Aguda , Glomerulonefrite por IGA , Insuficiência Renal Crônica , Masculino , Humanos , Criança , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/complicações , Imunoglobulina A , Incidência , Estudos Retrospectivos
7.
Acta Pharmacol Sin ; 44(9): 1777-1789, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37186122

RESUMO

Histone modification plays an important role in pathological cardiac hypertrophy and heart failure. In this study we investigated the role of a histone arginine demethylase, Jumonji C domain-containing protein 6 (JMJD6) in pathological cardiac hypertrophy. Cardiac hypertrophy was induced in rats by subcutaneous injection of isoproterenol (ISO, 1.2 mg·kg-1·d-1) for a week. At the end of the experiment, the rats underwent echocardiography, followed by euthanasia and heart collection. We found that JMJD6 levels were compensatorily increased in ISO-induced hypertrophic cardiac tissues, but reduced in patients with heart failure with reduced ejection fraction (HFrEF). Furthermore, we demonstrated that JMJD6 overexpression significantly attenuated ISO-induced hypertrophy in neonatal rat cardiomyocytes (NRCMs) evidenced by the decreased cardiomyocyte surface area and hypertrophic genes expression. Cardiac-specific JMJD6 overexpression in rats protected the hearts against ISO-induced cardiac hypertrophy and fibrosis, and rescued cardiac function. Conversely, depletion of JMJD6 by single-guide RNA (sgRNA) exacerbated ISO-induced hypertrophic responses in NRCMs. We revealed that JMJD6 interacted with NF-κB p65 in cytoplasm and reduced nuclear levels of p65 under hypertrophic stimulation in vivo and in vitro. Mechanistically, JMJD6 bound to p65 and demethylated p65 at the R149 residue to inhibit the nuclear translocation of p65, thus inactivating NF-κB signaling and protecting against pathological cardiac hypertrophy. In addition, we found that JMJD6 demethylated histone H3R8, which might be a new histone substrate of JMJD6. These results suggest that JMJD6 may be a potential target for therapeutic interventions in cardiac hypertrophy and heart failure.


Assuntos
Insuficiência Cardíaca , NF-kappa B , Animais , Ratos , Cardiomegalia/induzido quimicamente , Cardiomegalia/prevenção & controle , Cardiomegalia/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Histonas/metabolismo , Isoproterenol/toxicidade , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Ratos Sprague-Dawley , RNA Guia de Sistemas CRISPR-Cas , Volume Sistólico
8.
J Chem Phys ; 158(16)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37093143

RESUMO

Desorption of a self-propelling filament from an attractive surface is studied by computer simulations and the influence of activity, chain length, and chain rigidity is explored. For the flexible filament, we find three scaling regimes of desorption time vs activity with various scaling exponents. At low activity, the scaling law results from the spiral-like detachment kinetics. And at high activity, by theoretical analysis, the desorption is reminiscent of the escaping mechanism of a super-diffusive blob from a potential well at a short time scale. Additionally, the desorption time decreases first and then increases with chain length at low activity, since it is hard to form a spiral for short filaments due to the limited volume repulsion. For high activities, the desorption time approximately scales with chain length, with a scaling exponent ∼0.5, which can be explained by the theory and numerically fitting scaling law between the end-to-end distance of the "globule-like" filament and chain length. Furthermore, a non-monotonic behavior is observed between the desorption time and the chain stiffness. Desorption time slightly decreases first and then rapidly increases with stiffness due to the opposed effects of increasing rigidity on headiing-up time and leaving-away time. In contrast to traditional polymers, the scaling behavior suggests unique desorption characteristics of active polymers.

9.
Chem Biodivers ; 20(6): e202300301, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37097072

RESUMO

Two new indole diketopiperazine alkaloids (IDAs), (+)19-epi-sclerotiamide (1) and (-)19-epi-sclerotiamide (2), along with 13 known analogs (3-15), were isolated from a soft coral-associated epiphytic fungus Aspergillus versicolor CGF 9-1-2. The structures of two new compounds were established based on the combination of HR-ESI-MS, 1D and 2D NMR spectroscopy, optical rotation measurements and quantum chemical 13 C-NMR, the absolute configurations were determined by experimental and electronic circular dichroism (ECD) calculations. The results of molecular docking showed that all the compounds had a good binding with TDP1, TDP2, TOP1, TOP2, Ache, NLRP3, EGFR, EGFR L858R, EGFR T790M and EGFR T790/L858. Biological evaluation of compounds 3, 6, 8, 11 showed that 3 exerted a strong inhibitory effect on TDP2 with a rate of 81.72 %.


Assuntos
Agaricales , Antozoários , Neoplasias Pulmonares , Animais , Dicetopiperazinas/farmacologia , Dicetopiperazinas/química , Simulação de Acoplamento Molecular , Receptores ErbB/metabolismo , Mutação , Inibidores de Proteínas Quinases/metabolismo , Aspergillus/química , Alcaloides Indólicos/química , Antozoários/metabolismo , Estrutura Molecular
10.
Sensors (Basel) ; 23(5)2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36905042

RESUMO

The concentration of an electrolyte is an optical characteristic of drinking water. We propose a method based on the multiple self-mixing interference with absorption for detecting the Fe2+ indicator as the electrolyte sample at a micromolar concentration. The theoretical expressions were derived based on the lasing amplitude condition in the presence of the reflected lights considering the concentration of the Fe2+ indicator via the absorption decay according to Beer's law. The experimental setup was built to observe MSMI waveform using a green laser whose wavelength was located in the extent of the Fe2+ indicator's absorption spectrum. The waveforms of the multiple self-mixing interference were simulated and observed at different concentrations. The simulated and experimental waveforms both contained the main and parasitic fringes whose amplitudes varied at different concentrations with different degrees, as the reflected lights participated in the lasing gain after absorption decay by the Fe2+ indicator. The experimental results and the simulated results showed a nonlinear logarithmic distribution of the amplitude ratio, the defined parameter estimating the waveform variations, versus the concentration of the Fe2+ indicator via numerical fitting.

11.
J Bioenerg Biomembr ; 54(3): 155-162, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35676565

RESUMO

Thrombocytopenia and impaired platelet function are associated with sepsis-induced organ failure. Numerous studies have shown that mitochondrial ROS (mtROS) and autophagy are related to organ injury in sepsis. However, the relationships between platelet mtROS, autophagy and sepsis organ failure remain unclear. Herein, we explored whether toll like receptor 4 (TLR4) inhibitor alleviates sepsis organ failure by inhibiting platelet mtROS production, autophagy, and GPIIb/IIIa expression.Mice were administrated with LPS, LPS + TAK242 or vehicle. The lungs and kidneys were harvested and analyzed using hematoxylin and eosin staining assay. Platelet rich plasma (PRP) was isolated from blood and platelets aggregation and TLR4 expression were analyzed using flow cytometer and western blot. PRP from healthy volunteers was treated with saline, LPS, or LPS + TAK242, and then mitoSOX and calcium were detected using flow cytometer, and NOX2 and LC3B were tested using western blot.Results showed that TAK242 effectively alleviated LPS-induced acute kidney and lung injury in mice, and decreased CD41 expression more significantly than CD62P. In vitro, by inhibiting TLR4, TAK242 suppressed Ca2+, mitoSOX fluorescence, NOX2 expression and LC3BII/LC3BI ratio in LPS treated platelets.TLR4 inhibitor TAK242 may effectively alleviate mouse lung and kidney injury by inhibition of mouse platelet GPIIb/IIIa, and reduce LPS-induced mtROS generation related to Ca2+ influx, thus reducing platelet activation.


Assuntos
Sepse , Receptor 4 Toll-Like , Animais , Autofagia , Plaquetas/metabolismo , Humanos , Lipopolissacarídeos/toxicidade , Camundongos , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo , Receptor 4 Toll-Like/metabolismo
12.
Exp Brain Res ; 240(1): 97-111, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34661743

RESUMO

This study aimed to establish the role of miR-129 and miR-384-5p in cerebral ischemia-induced apoptosis. Using PC12 cells transfected with miR-129 or miR-384-5p mimics or inhibitors, oxygen glucose deprivation (OGD) conditions were applied for 4 h to simulate transient cerebral ischemia. Apoptotic phenotypes were assessed via lactate dehydrogenase (LDH) assay, MTT cell metabolism assay, and fluorescence-activated cell sorting (FACS). The effect of miR overexpression and inhibition was evaluated by protein and mRNA detection of bcl-2 and caspase-3, critical apoptosis factors. Finally, the direct relationship of miR-129 and bcl-2 and miR-384-5p and caspase-3 was measured by luciferase reporter assay. The overexpression of miR-384-5p and miR-129 deficiency significantly enhanced cell viability, reduced LDH release, and inhibited apoptosis. By contrast, overexpression of miR-129 and miR-384-5p deficiency aggravated hypoxia-induced apoptosis and cell injury. miR-129 overexpression significantly reduced mRNA and protein levels of bcl-2 and miR-129 inhibition significantly increased mRNA and protein levels of bcl-2 in hypoxic cells.miR-384-5p overexpression significantly reduced protein levels of caspase-3 while miR-384-5p deficiency significantly increased protein levels of caspase-3. However, no changes were observed in caspase-3 mRNA in either transfection paradigm. Finally, luciferase reporter assay confirmed caspase-3 to be a direct target of miR-384-5p; however, no binding activity was detected between bcl-2 and miR-129.Transient cerebral ischemia induces differential expression of miR-129 and miR-384-5p which influences apoptosis by regulating apoptotic factors caspase-3 and bcl-2, thereby participating in the pathological mechanism of cerebral ischemia, and becoming potential targets for the treatment of ischemic cerebral injury in the future.


Assuntos
Glucose , MicroRNAs , Animais , Apoptose/genética , MicroRNAs/genética , Oxigênio , Células PC12 , Ratos
13.
Mar Drugs ; 20(7)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35877736

RESUMO

Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G-J (1-4), and five known analogs (5-9) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1-9 exhibited strong antifungal activities against Colletotrichum gloeosporioides with LD50 values from 0.61 µg/mL to 16.14 µg/mL. Meanwhile, all compounds were evaluated for their cytotoxic activities against human pancreatic cancer BXPC-3 and PANC-1 cell lines; as a result, compound 1 showed more significant cytotoxicities than the positive control against both cell lines. In addition, based on the analyses of the protein-protein interaction (PPI) network and Western blot, 1 could induce apoptosis by activating caspase 3 proteins (CASP3).


Assuntos
Citrinina , Penicillium , Animais , Carbono/metabolismo , Citrinina/química , Fungos , Humanos , Estrutura Molecular , Penicillium/química , Estrelas-do-Mar
14.
Chem Biodivers ; 19(6): e202200208, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35567462

RESUMO

γ-Aromatic butenolides (γ-AB) are an important type of structures found in many bioactive microbial secondary metabolites (SMs). γ-AB refer to a group of natural products (NPs) containing five-membered (unsaturated) lactones with 3-phenyl and 4-benzyl substituents. Their wide-range biological activities have inspired pharmaceutical chemists to explore its biosynthesis mechanisms and design strategies to construct the γ-AB skeleton. Recently, there are a great deal of interesting research progress on the structures, biological activities and biosynthesis of γ-AB. This review will focus on these aspects and summarize the important achievements of γ-AB from 1975 to 2021.


Assuntos
4-Butirolactona , Produtos Biológicos , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Produtos Biológicos/farmacologia , Lactonas/química
15.
Sensors (Basel) ; 22(19)2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36236571

RESUMO

In this study, a piezoelectric micromachined ultrasonic transducer (PMUT) is integrated with a microliter-sized volume-tunable Helmholtz resonator. The passive Helmholtz resonator is constructed using an SU8 photolithography-defined square opening plate as the neck portion, a 3D-printed hollow structure with a threaded insert nut, and a precision set screw to form the volume-controllable cavity of the Helmholtz resonator. The fabricated piezoelectric films acted as ultrasonic actuators attached to the surface of the neck SU8 plate. Experimental results show that the sound pressure level (SPL) and operation bandwidth could be effectively tuned, and a 200% SPL increase and twofold bandwidth enhancement are achieved when setting the cavity length to 0.75 mm compared with the open-cavity case. A modified Helmholtz resonator model is proposed to explain the experimental results. The adjusting factors of the effective mass and viscous damper are created to modify the existing parameters in the conventional Helmholtz resonator model. The relationship between the adjusting factors and cavity length can be described well using a two-term power series curve. This modified Helmholtz resonator model not only provides insight into this active-type Helmholtz resonator operation but also provides a useful estimation for its optimal design and fabrication.


Assuntos
Transdutores , Ultrassom , Desenho de Equipamento , Pressão
16.
Pharm Biol ; 60(1): 909-914, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35575436

RESUMO

CONTEXT: Red ginseng polysaccharide (RGP) is an active component of the widely used medicinal plant Panax ginseng C. A. Meyer (Araliaceae), which has displayed promising activities against cancer cells. However, the detailed molecular mechanism of RGP in ferroptosis is still unknown. OBJECTIVE: This study evaluates the effects of RGP in cancer cells. MATERIALS AND METHODS: A549 and MDA-MB-231 cells were used. Cell proliferation was measured by CCK-8 assay after being treated with RGP at concentrations of 0, 50, 100, 200, 400, 800 and 1600 µg/mL at 0, 12, 24 and 48 h. Lipid reactive oxygen species (ROS) levels were assessed by C11-BODIPY assay. The control group was treated with PBS. RESULTS: RGP inhibited human A549 (IC50: 376.2 µg/mL) or MDA-MB-231(IC50: 311.3 µg/mL) proliferation and induced lactate dehydrogenase (LDH) release, promoted ferroptosis and suppressed the expression of GPX4. Moreover, the effects of RGP were enhanced by the ferroptosis inducer erastin, while abolished by ferroptosis inhibitor ferrostatin-1. DISCUSSION AND CONCLUSIONS: Our study is the first to demonstrate (1) the anticancer activity of RGP in human lung cancer and breast cancer. (2) RGP presented the anti-ferroptosis effects in lung and breast cancer cells via targeting GPX4.


Assuntos
Neoplasias da Mama , Ferroptose , Panax , Neoplasias da Mama/tratamento farmacológico , Regulação para Baixo , Feminino , Humanos , Polissacarídeos/farmacologia
17.
Can J Infect Dis Med Microbiol ; 2022: 2193430, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36329985

RESUMO

Objective: To explore the effect of transparent supervision model on the prevention and control of carbapenem-resistant Klebsiella pneumoniae (CRKP) nosocomial infection and the value of the autoregressive integrated moving average (ARIMA) model in predicting the incidence of CRKP infection. Methods: A total of 46,873 inpatients from Jiawang District People's Hospital of Xuzhou between January 2019 and December 2019 (prior to COVID-19 prevention and control) were selected as the preintervention group and 45,217 inpatients from January 2020 to December 2020 (after the COVID-19 prevention and control) as the postintervention group. We performed transparent supervision on CRKP patients detected by the real-time monitoring system for nosocomial infection. Incidence and detection rate of CRKP, utilization rate of special grade hydrocarbon enzyme alkene antibiotics, hand hygiene compliance rate, qualified rate of ATP tests on surface of environmental objects, and execution rate of CRKP core prevention and control were compared between the two groups. Results: Transparent supervision of CRKP-infected patients was conducted daily from January to December 2020, which resulted in the following: (a) the infection rate of CRKP decreased in a fluctuating manner, and the actual value of hydrocarbon alkene use rate was basically the same as the predicted value with an overall decreasing trend; (b) after the intervention, hand hygiene compliance rate increased from 53.30% to 70.24% (P < 0.001) and the ATP qualified rate increased from 53.77% to 92.24% (P < 0.001); (c) the fitted value of the ARIMA model was in good agreement with the actual value. The incidence of CRKP infection and the utilization rate of carbene antibiotics were also in good agreement with the predicted value. The average relative errors were 11% and 10.78%. Conclusions: During the COVID-19 outbreak in 2020, the ARIMA model effectively fit and predicted the CRKP infection rate, thereby providing scientific guidance for the prevention and control of CRKP infection. In addition, the transparent supervision intervention model improved the hand hygiene compliance and environmental hygiene qualification rates of medical staff, effectively reducing CRKP cross-infection in the hospital.

18.
Insect Mol Biol ; 30(4): 400-409, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33837597

RESUMO

Proteins containing nuclear localization signals (NLSs) are actively transported into the nucleus via the classic importin-α/ß-mediated pathway, and NLSs are recognized by members of the importin-α family. Most studies of insect importin-αs have focused on Drosophila to date, little is known about the importin-α proteins in Lepidoptera insects. In this study, we identified four putative importin-α homologues, Spodoptera frugiperda importin-α1 (SfIMA1), SfIMA2, SfIMA4 and SfIMA7, from Sf9 cells. Immunofluorescence analysis showed that SfIMA2, SfIMA4 and SfIMA7 localized to the nucleus, while SfIMA1 distributed in cytoplasm. Additionally, SfIMA4 and SfIMA7 were also detected in the nuclear membrane of Sf9 cells. SfIMA1, SfIMA4 and SfIMA7, but not SfIMA2, were found to associate with the C terminus of AcMNPV DNA polymerase (DNApol) that harbours a typical monopartite NLS and a classic bipartite NLS. Further analysis of protein-protein interactions revealed that SfIMA1 specifically recognizes the bipartite NLS, while SfIMA4 and SfIMA7 bind to both monopartite and bipartite NLSs. Together, our results suggested that SfIMA1, SfIMA4 and SfIMA7 play important roles in the nuclear import of AcMNPV DNApol C terminus in Sf9 cells.


Assuntos
DNA Polimerase Dirigida por DNA/metabolismo , Nucleopoliedrovírus , Spodoptera , alfa Carioferinas/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Animais , Núcleo Celular/metabolismo , Núcleo Celular/virologia , Proteínas de Insetos/metabolismo , Sinais de Localização Nuclear/metabolismo , Nucleopoliedrovírus/genética , Nucleopoliedrovírus/metabolismo , Domínios e Motivos de Interação entre Proteínas , Células Sf9/metabolismo , Células Sf9/virologia , Spodoptera/metabolismo , Spodoptera/virologia , Proteínas Virais/metabolismo
19.
Acta Pharmacol Sin ; 42(7): 1111-1123, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33637947

RESUMO

Ionizing radiation-induced intestinal injury is a catastrophic complication in patients receiving radiotherapy. Circulating exosomes from patients undergoing radiotherapy can mediate communication between cells and facilitate a variety of pathological processes in vivo, but its effects on ionizing radiation-induced intestinal damage are undetermined. In this study we investigated the roles of exosomes during total body irradiation (TBI)-induced intestinal injury in vivo and in vitro. We isolated exosomes from serum of donor mice 24 h after lethal dose (9 Gy) TBI (Exo-IR-24h), then intravenously injected the exosomes into receipt mice, and found that Exo-IR-24h injection not only exacerbated 9 Gy TBI-induced lethality and weight loss, but also promoted crypt-villus structural and functional injury of the small intestine in receipt mice. Moreover, Exo-IR-24h injection significantly enhanced the apoptosis and DNA damage of small intestine in receipt mice following TBI exposure. In murine intestinal epithelial MODE-K cells, treatment with Exo-IR-24h significantly promoted 4 Gy ionizing radiation-induced apoptosis, resulting in decreased cell vitality. We further demonstrated that Exo-IR-24h promoted the IR-induced injury in receipt mice partially through its DNA damage-promoting effects and attenuating Nrf2 antioxidant response in irradiated MODE-K cells. In addition, TBI-related miRNAs and their targets in the exosomes of mice were enriched functionally using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, injection of GW4869 (an inhibitor of exosome biogenesis and release, 1.25 mg·kg-1·d-1, ip, for 5 consecutive days starting 3 days before radiation exposure) was able to rescue mice against 9 Gy TBI-induced lethality and intestinal damage. Collectively, this study reveals that exosomes are involved in TBI-induced intestinal injury in mice and provides a new target to protect patients against irradiation-induced intestinal injury during radiotherapy.


Assuntos
Exossomos/metabolismo , Enteropatias/metabolismo , Mucosa Intestinal/metabolismo , Animais , Apoptose/fisiologia , Proliferação de Células/fisiologia , Dano ao DNA/fisiologia , Raios gama , Enteropatias/patologia , Mucosa Intestinal/patologia , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Lesões Experimentais por Radiação , Irradiação Corporal Total
20.
Luminescence ; 36(7): 1600-1607, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34018312

RESUMO

As an unnecessary trace element, the content of aluminium in biological systems should be strictly controlled. Therefore, it was necessary to develop a convenient method for detection of aluminium ions. In this study, a fluorescent probe based on polythiophene derivatives was developed and used to detect Al3+ in Chinese traditional pasta. The fluorescence of this probe showed a significant decrease in hexamethylenetetramine-HCl buffer solution (pH 5) when Al3+ was present. In addition, the probe exhibited good sensitivity and selectivity to Al3+ over other metal ions when EDTA was used as the masking agent. Fluorescence intensity had a good linear relationship with the Al3+ concentration in the range 0.1-10 µM and the limit of detection for Al3+ was 39 nM. Furthermore, the probe was successfully applied to detect Al3+ in food samples and the results were consistent with ICP-AES.


Assuntos
Corantes Fluorescentes , Triticum , Ácidos Fosforosos , Polímeros , Espectrometria de Fluorescência , Tiofenos
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