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microRNAs (miRs) are essential in the development of heart failure. The aim of this study is to investigate the effect of microRNA-330 (miR-330) on left ventricular remodeling via the TGF-ß1/Smad3 signaling pathway by targeting the sex-determining region Y (SRY) in mice with myocardial ischemia-reperfusion injury (MIRI). Differentially expressed gene (DEG) in myocardial ischemia-reperfusion (IR) was screened out and the miR that targeted the DEG was also predicted and verified. A model of MIRI was established to detect the expression of miR-330, SRY, transforming growth factor-ß (TGF-ß1), and Sekelsky mothers against dpp3 (Smad3). To further investigate the role of miR-330 in MIRI with the involvement of SRY and TGF-ß1/Smad3 signaling pathway, the modeled mice were treated with different mimic, inhibitor, or small interfering RNA (siRNA) to observe the changes of the related gene expression, as well as the myocardial infarction size and volume of myocardial collagen. SRY was screened out and verified as a target gene of miR-330. The MIRI mice showed enlarged myocardial infarction size, increased volume of myocardial collagen, increased expression of miR-330, TGF-ß1 and Smad3, while decreased the expression of SRY. The MIRI mice treated with miR-330 inhibitor showed decreased myocardial infarction size, the volume of myocardial collagen, and expression of TGF-ß1 and Smad3 but promoted expression of SRY. Our findings demonstrated that downregulated miR-330 could suppress left ventricular remodeling to inhibit the activation of the TGF-ß1/Smad3 signaling pathway via negatively targeting of SRY in mice with MIRI. This can be a potential target in the strategy to attenuate patient suffering.
Assuntos
MicroRNAs/metabolismo , Isquemia Miocárdica/patologia , Proteína da Região Y Determinante do Sexo/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Remodelação Ventricular , Animais , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Isquemia Miocárdica/metabolismo , Distribuição Aleatória , Traumatismo por Reperfusão , Proteína da Região Y Determinante do Sexo/genética , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genéticaRESUMO
In circular waveguides, the TE01 mode has the lowest transmission loss, which is very suitable for long-distance transmission of high-power microwaves (HPMs). The output mode of HPM sources is mainly the TM01 mode; however, there are few research studies on mode converters of TM01-TE01. In this paper, a high efficiency HPM TM01-TE01 mode converter is designed; compared with the traditional TM01-TE01 mode converters, the structure of the mode converter is compact and easier to process. It is mainly composed of an input circular waveguide, a tapered rectangular waveguide, a 90° bent rectangular waveguide, and an output circular waveguide. A prototype with a center frequency of 2.4 GHz is fabricated and HPM experiments are carried out. The transmission efficiency of this device reaches 99.8% in the simulation, and the measured transmission efficiency is more than 98%. Additionally, the measured power handling capacity is more than 1 GW, which is consistent with simulation. This design has important reference significance for the design of long-distance power transmission devices and HPM mode converters.
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Stem cell-based therapy raises hopes for a better approach to promoting tissue repair and functional recovery. However, transplanted stem cells show a high death percentage, creating challenges to successful transplantation and prognosis. Thus, it is necessary to investigate the mechanisms underlying stem cell death, such as apoptotic cascade activation, excessive autophagy, inflammatory response, reactive oxygen species, excitotoxicity, and ischemia/hypoxia. Targeting the molecular pathways involved may be an efficient strategy to enhance stem cell viability and maximize transplantation success. Notably, a more complex network of cell death receives more attention than one crucial pathway in determining stem cell fate, highlighting the challenges in exploring mechanisms and therapeutic targets. In this review, we focus on programmed cell death in transplanted stem cells. We also discuss some promising strategies and challenges in promoting survival for further study.
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Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors that are harmful to human health. Increasing evidence has underscored the critical role of the competitive endogenous RNA (ceRNA) regulatory networks among various human cancers. However, the complexity and behavior characteristics of the ceRNA network in HCC were still unclear. In this study, we aimed to clarify a phosphatase and tensin homolog (PTEN)-related ceRNA regulatory network and identify potential prognostic markers associated with HCC. The expression profiles of three RNAs (long non-coding RNAs [lncRNAs], microRNAs [miRNAs], and mRNAs) were extracted from The Cancer Genome Atlas (TCGA) database. The DLEU2L-hsa-miR-100-5p/ hsa-miR-99a-5p-TAOK1 ceRNA network related to the prognosis of HCC was obtained by performing bioinformatics analysis. Importantly, we identified the DLEU2L/TAOK1 axis in the ceRNA by using correlation analysis, and it appeared to become a clinical prognostic model by Cox regression analysis. Furthermore, methylation analyses suggested that the abnormal upregulation of the DLEU2L/TAOK1 axis likely resulted from hypomethylation, and immune infiltration analysis showed that the DLEU2L/TAOK1 axis may have an impact on the changes in the tumor immune microenvironment and the development of HCC. In summary, the current study constructing a ceRNA-based DLEU2L/TAOK1 axis might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC.
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Surface-enhanced Raman spectra of methylene blue (MB) at different concentrations in silver colloid were obtained. The results indicate that the physical adsorption is dominant at high concentration while the chemical adsorption is the main fashion at relatively low concentration; there are different adsorption orientations at different concentration: MB+ molecule is perpendicular to the surface of silver nanoparticle at high concentration and adopts a parallel orientation on the surface of nanoparticle at low concentration. The effect of adsorbing time of MB molecule in Ag colloid was investigated and the adsorption dynamics study shows that the parallel orientation at low concentration does not change with the adsorbing time increasing. Density functional theory (DFT) calculations at the level of B3LYP/6-311+G * (for C, S, N, H)/LANL2DZ (for Ag) were employed to optimize the structures and predict Raman frequencies of MB+ and various MB+ -Ag complexes. The results of experiments and calculations suggest that the silver atom prefers to be bound to N and S atoms in the aromatic ring, and thus two different complexes are formed, i.e., conformer N-Ag and conformer S-Ag. Moreover, the Mulliken charge population analysis indicates that N atom in the aromatic ring prefers to interact with Ag than S atom does. Finally, the Raman frequencies observed in the experiments and their vibrational modes were tentatively assigned and discussed.
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The mol-ecule of the title compound, C(6)H(6)N(4)O(4), is almost planar, being stabilized by two intra-molecular N-Hâ¯O hydrogen bonds. Further N-Hâ¯O links lead to a sheet in the crystal structure.
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The purpose of this study was to investigate the effect of inhibition of calpain on retinal ganglion cell-5 (RGC-5) necroptosis following oxygen glucose deprivation (OGD). RGC-5 cells were cultured in Dulbecco's-modified essential medium and necroptosis was induced by 8-h OGD. PI staining and flow cytometry were performed to detect RGC-5 necrosis. The calpain expression was detected by Western blotting and immunofluorescence staining. The calpain activity was tested by activity detection kit. Flow cytometry was used to detect the effect of calpain on RGC-5 necroptosis following OGD with or without N-acetyl-leucyl-leucyl-norleucinal (ALLN) pre-treatment. Western blot was used to detect the protein level of truncated apoptosis inducing factor (tAIF) in RGC-5 cells following OGD. The results showed that there was an up-regulation of the calpain expression and activity following OGD. Upon adding ALLN, the calpain activity was inhibited and tAIF was reduced following OGD along with the decreased number of RGC-5 necroptosis. In conclusion, calpain was involved in OGD-induced RGC-5 necroptosis with the increased expression of its downstream molecule tAIF.
Assuntos
Fator de Indução de Apoptose/genética , Calpaína/genética , Células Ganglionares da Retina/metabolismo , Síndrome de Necrose Retiniana Aguda/genética , Animais , Fator de Indução de Apoptose/biossíntese , Calpaína/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Humanos , Leupeptinas/administração & dosagem , Camundongos , Oxigênio/metabolismo , Células Ganglionares da Retina/patologia , Síndrome de Necrose Retiniana Aguda/patologiaRESUMO
OBJECTIVE: This study was to explore the use value of (18)F-FDG PET/CT in patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: Both PET/CT and CT images were retrospectively analyzed in 43 newly diagnosed patients with ENKTL, and the anatomical position, extent of foci, subtypes, staging and therapeutic regimen determined by both these 2 imaging methods were compared, and relationship between the maximum standard uptake value (SUV(max)) and subtypes, different staging and constitutional symptoms were evaluated. RESULTS: The top four anatomical positions involved were nose (76.74%), pharynx nasalis (41.86%), Waldeyer's ring (30.23%) and paranasal sinus (27.91%), respectively according to the results of the PET/CT examination, and (18)F-FDG uptake was not found in four patients in the region of upper aerodigestive tract. The PET/CT staging was significantly correlated with constitutional symptoms (P < 0.01). The mean SUV(max) of 43 patients was 13.65 ± 6.35, and the SUV(max) of advanced stages (III/IV) was higher than that of early stage (I/II). Different staging results were found in 21 patients between PET/CT and CT images, 14 patients out of them had direct influence on the treatment plan. Staging of 8 cases was changed from early stage judged by CT image into advaneed stage judged by PET/CT, and radiotherapy regimen of 6 cases at early stage were altered because of the application of PET/CT. CONCLUSION: The location and scope of foci in ENKTL patients can be displayed more accurately by PET/CT, the PET/CT is more accurate and reliable than traditional CT image, and has considerable value in determining the treatment plan, and it should be applied in clinical practice widely.
Assuntos
Linfoma Extranodal de Células T-NK , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Fluordesoxiglucose F18 , Humanos , Imagem Multimodal , Estudos RetrospectivosRESUMO
BACKGROUND: It has been well demonstrated that plant growth regulators have important functions in multiple physiological processes. ABA and BR play crucial roles in response of crops to stresses. Photosynthetic capacity of Leymus. chinensis treated by various concentrations of ABA and BR in combination was determined. Further more, the mechanisms of ABA and BR treatments and potential for recovery of saline-alkali grasslands were discussed. RESULTS: Abscisic acid (ABA) and brassinolide (BR) affected leaf gas exchange, growth and biomass of L. chinensis. The application of ABA and BR mixtures, especially that of 0.01 mM ABA and 2 × 10-4 mM BR, increased the net photosynthetic rate, stomatal conductance, water use efficiency, the maximum net photosynthetic rate, light-saturated rate, leaf respiration rate, the maximum RUBP carboxylation rate, the maximum electron transport rate, the maximum triose-phosphate utilization, carboxylation efficiency and the quantum efficiency of PSII and subsequently enhanced density, height and biomass in L. chinensis. We also observed reduction in the light compensation and saturation points following the application of ABA and BR treatments. CONCLUSIONS: We concluded that proper use of plant growth regulators can enhance the plant growth and productivity on the Songnen grassland, which is particularly important for the improvement of saline - alkaline grassland and the yield of grazing lands.
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This study aimed to investigate the pathophysiological changes in a rat chronic heart failure complicated with renal failure model, caused by three-quarters nephrectomy and subcutaneous injection of isoproterenol (ISO). Sprague-Dawley (SD) rats in the model group received three-quarters nephrectomy after twice undergoing surgical resections and subcutaneous injection of ISO (100 mg/kg body weight, injected twice, with a 24 h interval) after one week, while rats in the control group received sham surgery and injection of normal saline. Survival rate, heart failure and renal failure were compared between the two groups after 4 weeks. Serum creatinine (Cr), blood urea nitrogen (BUN), B-type natriuretic protein (BNP), aldolase (ALD), angiotensin II (Ang II) and C-reactive protein (CRP) were determined by kit assay. Urine protein at 24 h was determined by the Bradford method and left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP) and left ventricular end-diastolic pressure (LVEDP), as well as the maximum rates of increased and decreased left ventricular pressure (±dP/dt(max)) were determined by left ventricular intubation. Heart weight indices were determined and the myocardial pathological conditions were observed by hematoxylin and eosin (HE) staining. There was no death in the control group, while the survival rate of the model group was 73%. Compared with the control group, each index of serum and urine protein in the model group was significantly increased. Additionally, LVSP was decreased, LVDP and LVEDP were increased and heart weight index was increased, with a significant difference. The serum Cr was positively correlated to BNP levels in the model group. Three-quarters nephrectomy and subcutaneous injection of ISO induces left ventricular heart failure and renal failure at the same time, which is characterized in pathophysiology by left ventricular diastolic and systolic function failure, left ventricular myocardial hypertrophy and reconstruction complicated with renal insufficiency.