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Anesthetics exposure induces neurocognitive deficits during brain development and impairs self-renewal and differentiation of neural stem cells (NSCs). Tripartite motif 72 (TRIM72, also known as mitsugumin 53, MG53) is involved in tissue repair and plasma membrane damage repair. The neuroprotective effect of TRIM72 against sevoflurane-induced neurotoxicity of NSCs was investigated in this study. First, human NSCs were exposed to different concentrations of sevoflurane. Results showed that TRIM72 was downregulated in sevoflurane-treated NSCs. Exposure to sevoflurane reduced cell viability in NSCs. Second, sevoflurane-treated NSCs were stimulated with recombinant human TRIM72 (rhTRIM72). Treatment with rhTRIM72 enhanced the cell viability in sevoflurane-treated NSCs. Moreover, treatment with a rhTRIM72-attenuated sevoflurane-induced increase in caspase-3 activity in NSCs. Third, JC-1 aggregates were deceased and JC-1 monomer was increased in sevoflurane-treated NSCs, which were reversed by rhTRIM72. Furthermore, rhTRIM72 also weakened sevoflurane-induced decrease in superoxide dismutase and glutathione peroxidase and increase in malondialdehyde and reactive oxygen species in NSCs. Finally, reduced phosphorylation levels of protein kinase B (AKT) and phosphatidylinositol 3-kinase (PI3K) in sevoflurane-treated NSCs were upregulated by rhTRIM72. In conclusion, TRIM72 inhibited cell apoptosis and reduced the mitochondria membrane potential of sevoflurane-treated NSCs through activation of the PI3K/AKT pathway.
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Anestésicos , Células-Tronco Neurais , Sevoflurano , Proteínas com Motivo Tripartido , Humanos , Anestésicos/farmacologia , Apoptose , Mitocôndrias , Células-Tronco Neurais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sevoflurano/farmacologia , Transdução de Sinais , Proteínas com Motivo Tripartido/metabolismoRESUMO
Neuroinflammation plays a dominant role in the progression of postoperative cognitive dysfunction (POCD). Vitamin D has been known to have important regulatory functions in inflammation and immune response. The NOD-like receptor protein 3 (NLRP3) is an essential inflammasome in the inflammatory response and could be activated by anesthesia and surgery. In this study, male C57BL/6 mice aged 14-16 months were given VD3 for 14 days straight before having an open tibial fracture surgery. The animals were either sacrificed to obtain the hippocampus or tested in a Morris water maze test. Western blot was employed to estimate the levels of NLRP3, ASC, and caspase-1, immunohistochemistry was used to identify microglial activation, and an enzyme-linked immunosorbent assay was used to measure the expression of IL-18 and IL-1ß, while using the corresponding assay kits to assess ROS and MDA levels to reflect the oxidative stress status. We showed that VD3 pretreatment significantly improved surgery-induced memory and cognitive dysfunctions in aged mice, which was linked to the inactivation of the NLRP3 inflammasome and the inhibition of neuroinflammation. This finding provided a novel preventative strategy for clinically reducing postoperative cognitive impairment in elderly surgical patients. This study has some limitations. Gender differences in the effects of VD3 were not considered, and only male mice were used. Additionally, VD3 was given as a preventative measure; however, it is unknown whether it has any therapeutic benefits for POCD mice. This trial is registered with ChiCTR-ROC-17010610.
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Disfunção Cognitiva , Complicações Cognitivas Pós-Operatórias , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Colecalciferol/uso terapêutico , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Disfunção Cognitiva/tratamento farmacológico , Suplementos NutricionaisRESUMO
Iron plaque is the amorphous and/or crystalline layer of Fe and Mn (hydr)oxides formed on the root surface of wetland plants. It could adsorb and co-precipitate metal(loid)s at the rhizosphere, thus modulating the uptake and accumulation of metal elements in plants. In this study, the Fe(II)/Mn(II)-oxidizing bacteria Burkholderia sp. D416 (D416) and Pseudomonas sp. YGL (YGL) were isolated from Cd-contaminated rice field, both hydroponic experiment and pot experiment were performed to assess the impact of bacterial inoculation on iron plaque formation, elemental content of the plaque, plant dry mass, antioxidant enzyme activity and Cd content in rice plants. The results revealed that inoculation with D416, YGL, and D416+YGL stimulated iron plaque formation on the root surface of the hydroponic rice. The content of C, N, O, Na, Mg, Al, Si, P, S, Cl, K, Fe and Ca in the root plaque were affected by the bacterial inoculation and varied among different plant growth stages. The pot experiment indicated that inoculation with D416 increased the root dry biomass by 58.89%, and the combined inoculation of D416 and YGL increased the dry biomass of root, shoot and grain by 16.89%, 21.66% and 23.26%, respectively. Importantly, YGL inoculation decreased the Cd translocation from root to shoot and from glume to brown rice grain by 50.00% and 50.27%, respectively, and the Cd content in shoot and brown rice grain were decreased by 20.00% and 34.48%, respectively. Taken together, the elemental content of the iron plaque and Cd content in rice plants varied among different plant growth stages and when plants were inoculated with different bacterial strains. YGL dramatically reduced the Cd content in brown rice grain, thus it could potentially be used to reduce Cd content in rice crop grown in Cd-contaminated soils.
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Oryza , Poluentes do Solo , Bactérias , Cádmio/análise , Ferro , Manganês , Oxirredução , Raízes de Plantas/química , Rizosfera , Solo , Poluentes do Solo/análiseRESUMO
To investigate the role of miR-128-3p and MAPK14 in the dexmedetomidine treatment of acute lung injury in septic mice. SPF C57BL/6 mice were divided into 8 groups. The pathological changes and wet/dry weight ratio (W/D), PaO2, PaCO2, MDA, SOD and MPO levels in lung tissue and the serum levels of inflammation factors were observed. Dual luciferase reporter assay was used to detect the targeting relationship of miR-128-3p and MAPK14, and qPCR and WB were used to detect the expression of miR-128-3p and MAPK14. Compared with the Normal group, other groups had lower MDA, MPO, inflammatory factors levels and the expression level of MAPK14, while the content of SOD and the expression level of miR-128-3p was significantly decreased (all p < 0.05). Compared with the Model group, the contents of MDA, MPO, inflammatory factors in the DEX group and miR-128-3p mimic group were significantly decreased, and the content SOD was significantly increased, however, opposite results were occurred in oe-MAPK14 group (all p < 0.05). Compared with the DEX group, all the indicators in miR-128-3p mimic+DEX group showed significant improvement (all p < 0.05). Compared with the miR-128-3p mimic group, all the indicators were deteriorated in the miR-128-3p mimic+oe-MAPK14 group (all p < 0.05). The combination of DEX and oe-MAPK14 blocked the protective effect of dexmedetomidine on acute lung injury in septic mice. miR-128-3p can further enhance the protective effect of dexmedetomidine on acute lung injury in septic mice by targeting and inhibiting MAPK14 expression.
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Lesão Pulmonar Aguda/tratamento farmacológico , Dexmedetomidina/farmacologia , MicroRNAs/metabolismo , Proteína Quinase 14 Ativada por Mitógeno/antagonistas & inibidores , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/enzimologia , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Analgésicos não Narcóticos/farmacologia , Animais , Masculino , Camundongos , MicroRNAs/genética , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Sepse/enzimologia , Sepse/genética , Sepse/metabolismoRESUMO
Raltegravir (RAL) is a first clinically approved integrase (IN) inhibitor for the treatment of HIV but rapid mutation of the virus has led to chemo-resistant strains. Therefore, there is a medical need to develop new IN inhibitors to overcome drug resistance. At present, several IN inhibitors are in different phases of clinical trials and few have been discontinued due to toxicity and lack of efficacy. The development of potent second-generation IN inhibitors with improved safety profiles is key for selecting new clinical candidates. In this article, we report the design and synthesis of potent 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide analogues as second-generation IN inhibitors. These compounds satisfy two structural requirements known for potent inhibition of HIV-1 IN catalysis: a metal chelating moiety and a hydrophobic functionality necessary for selectivity against the strand transfer reaction. Most of the new compounds described herein are potent and selective for the strand transfer reaction and show antiviral activity in cell-based assays. Furthermore, this class of compounds are drug-like and suitable for further optimization and preclinical studies.
Assuntos
Descoberta de Drogas , Inibidores de Integrase de HIV/farmacologia , Integrase de HIV/metabolismo , HIV/efeitos dos fármacos , Pirimidinas/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores de Integrase de HIV/síntese química , Inibidores de Integrase de HIV/química , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-AtividadeRESUMO
Glucagonomas are rare neuroendocrine neoplasms of the pancreas with malignant potential. At present, their epidemiology is not entirely clear, so clinicians are not well versed, lacking any consensus on diagnosis or comprehensive treatment. The present study reports the case of a 32-year-old woman hospitalized for recurrent glossitis, perioral dermatitis and necrolytic migratory erythema (NME) of both lower limbs. Imaging studies revealed a low-density nodule (~2 cm) in the tail of the pancreas, as well as multiple space-occupying hepatic lesions. Surgical intervention was then selected, and distal pancreatectomy, splenectomy and palliative metastasectomies were performed. Tissue examination subsequently confirmed a primary pancreatic neuroendocrine tumor (grade 2), metastatic to the liver. The NME resolved postoperatively, aided by intramuscular injections of long-acting release octreotide (30 mg) every 28 days. A series of three percutaneous ablative treatments (microwave ablation) were also undertaken within a 2-year period, targeting the liver metastases. The present condition of the patient is good, with no cutaneous relapse to date. Palliative metastasectomies, in conjunction with ablative treatments and combination somatostatin analog (SSA) use, are unique aspects of this case that, to the best of our knowledge, have yet to be documented in the literature. Surgical palliation may benefit patients with liver involvement and prolong their survival time. Likewise, ablative treatments and SSA injections delivered together not only address hepatic spread, but also control hormone-related symptoms, having a positive impact on prognosis. As glucagonomas are so rare, there is no real agreement on their management. The present study aims to guide clinical practice by adding further to the available data.
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Excessive phosphorus will lead to eutrophication in aquatic environment; the efficient removal of phosphorus is crucial for wastewater engineering and surface water management. This study aimed to fabricate a nanorod-like sepiolite-supported MgO (S-MgO) nanocomposite with high specific surface area for efficient phosphate removal using a facile microwave-assisted method and calcining processes. The impact of solution pH, adsorbent dosage, contact time, initial phosphate concentrations, Ca2+ addition, and N/P ratio on the phosphate removal was extensively examined by the batch experiments. The findings demonstrated that the S-MgO nanocomposite exhibited effective removal performance for low-level phosphate (0 ~ 2.0 mM) within the pH range of 3.0 ~ 10.0. Additionally, the nanocomposite can synchronously remove phosphate and ammonium in high-level nutrient conditions (> 2.0 mM), with the maximum removal capacities of 188.49 mg P/g and 89.78 mg N/g. Quantitative and qualitative analyses confirmed the successful harvesting of struvite in effluent with high-phosphate concentrations, with the mechanisms involved attributed to a synergistic combination of sorption and struvite crystallization. Due to its proficient phosphate removal efficiency, cost-effectiveness, and substantial removal capacity, the developed S-MgO nanocomposite exhibits promising potential for application in phosphorus removal from aquatic environments.
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Silicatos de Magnésio , Nanocompostos , Poluentes Químicos da Água , Fósforo/química , Estruvita/química , Óxido de Magnésio , Nitrogênio , Fosfatos/químicaRESUMO
After coal combustion, the minerals present in fly ash can adsorb arsenic (As) during flue gas cooling and reduce As emissions. However, a quantitative description of this adsorption behavior is lacking. Herein, the As adsorption characteristics of minerals (Al/Ca/Fe/K/Mg/Na/Si) were investigated, and a model was developed to predict As content in fly ash. Lab-scale experiments and density functional theory calculations were performed to obtain mineral As adsorption potential. Then, the model was established using lab-scale experimental data for 11 individual coals. The model was validated using lab-scale data from ten blended coals and demonstrated acceptable performance, with prediction errors of 2.83-11.45 %. The model was applied to a 350 MW coal-fired power plant (CFPP) with five blended coals, and As concentration in the flue gas was predicted from a mass balance perspective. The experimental and predicted As contents in fly ash were 11.92-16.15 and 9.61-12.55 µg/g, respectively, with a prediction error of 17.39-22.29 %, and those in flue gas were 11.52-16.58 and 5.37-34.04 µg/Nm3. Finally, As distribution in the CFPP was explored: 0.74-1.51 % in bottom ash, 74.05-82.70 % in electrostatic precipitator ash, 0.53-1.19 % in wet flue gas desulfurization liquid, and 0.13-0.73 % in flue gas at the stack inlet.
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Coal combustion is the major contributor to global toxic selenium (Se) emissions. Inorganic elements in coals significantly affect Se partitioning during combustion. This work confirmed that the calcium (Ca) in ash had a stronger relationship with Se retention at 1300 °C than other major elements. Ca oxide chemically reacted with gaseous Se, and its sintering densification slightly affected Se adsorption capacities (44.45 -1840.71â35.17 -1540.15 mg/kg) at 300 - 1300 °C. Therefore, Ca in coals was identified as having potential for hindering gaseous Se emissions, and coals with increased Ca contents (2.74â5.19 wt%) were used in a 350 MW unit. The decreased Se mass distribution (3.54%â2.63%) in flue gas at air preheater inlet (320 -362 °C) confirmed the effectiveness of increased Ca content on gaseous Se emission reduction. More gaseous Se further condensed and was chemically adsorbed by fly ash when passed through an electrostatic precipitator, resulting in a significant increase in the Se content of fly ash. Additionally, the corresponding Se leaching ratio decreased from 4.88 - 35.74% to 1.87 - 26.31%, indicating enhanced stability of Se enriched in fly ash. This research confirmed the feasibility and environmental safety of sequestration of gaseous Se from flue gas to fly ash by increasing the Ca content in coals.
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BACKGROUND: White matter injury (WMI) is an important pathological process after traumatic brain injury (TBI). The correlation between white matter functions and the myeloid cells expressing triggering receptor-2 (TREM2) has been convincingly demonstrated. Moreover, a recent study revealed that microglial sterol metabolism is crucial for early remyelination after demyelinating diseases. However, the potential roles of TREM2 expression and microglial sterol metabolism in WMI after TBI have not yet been explored. METHODS: Controlled cortical injury was induced in both wild-type (WT) and TREM2 depletion (TREM2 KO) mice to simulate clinical TBI. COG1410 was used to upregulate TREM2, while PLX5622 and GSK2033 were used to deplete microglia and inhibit the liver X receptor (LXR), respectively. Immunofluorescence, Luxol fast blue staining, magnetic resonance imaging, transmission electron microscopy, and oil red O staining were employed to assess WMI after TBI. Neurological behaviour tests and electrophysiological recordings were utilized to evaluate cognitive functions following TBI. Microglial cell sorting and transcriptomic sequencing were utilized to identify alterations in microglial sterol metabolism-related genes, while western blot was conducted to validate the findings. RESULTS: TREM2 expressed highest at 3 days post-TBI and was predominantly localized to microglial cells within the white matter. Depletion of TREM2 worsened aberrant neurological behaviours, and this phenomenon was mediated by the exacerbation of WMI, reduced renewal of oligodendrocytes, and impaired phagocytosis ability of microglia after TBI. Subsequently, the upregulation of TREM2 alleviated WMI, promoted oligodendrocyte regeneration, and ultimately facilitated the recovery of neurological behaviours after TBI. Finally, the expression of DHCR24 increased in TREM2 KO mice after TBI. Interestingly, TREM2 inhibited DHCR24 and upregulated members of the LXR pathway. Moreover, LXR inhibition could partially reverse the effects of TREM2 upregulation on electrophysiological activities. CONCLUSIONS: We demonstrate that TREM2 has the potential to alleviate WMI following TBI, possibly through the DHCR24/LXR pathway in microglia.
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Lesões Encefálicas Traumáticas , Glicoproteínas de Membrana , Microglia , Receptores Imunológicos , Substância Branca , Animais , Masculino , Camundongos , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/genética , Modelos Animais de Doenças , Receptores X do Fígado/metabolismo , Receptores X do Fígado/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Substância Branca/metabolismo , Substância Branca/patologiaRESUMO
A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds could occupy the IN active site and form pi-pi interactions with viral DNA nucleotides DC16 and DA17 to displace reactive viral DNA 3'OH and block intasome activity.
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Inibidores de Integrase de HIV/química , Inibidores de Integrase de HIV/farmacologia , HIV-1/enzimologia , Pirimidinonas/química , Pirimidinonas/farmacologia , Domínio Catalítico , DNA Viral/química , DNA Viral/metabolismo , Inibidores de Integrase de HIV/síntese química , HIV-1/química , HIV-1/efeitos dos fármacos , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Pirimidinonas/síntese químicaRESUMO
A novel hierarchically nanostructured magnetite (Fe3O4) was manufactured using microwave-assisted reflux method without surfactants. The nanostructured Fe3O4 is formed via the co-precipitation of Fe(III) and Fe(II), followed by a nanocrystal aggregation-based mechanism. Moreover, the effects of solution pH, contact time, initial Sb concentration, coexisting anions, and recycle numbers on the adsorption of nanostructured Fe3O4 toward Sb were extensively examined in the batch adsorption tests. The results demonstrated that the obtained Fe3O4 exhibited excellent adsorption ability toward Sb with the maximum adsorption capacities of 154.2 and 161.1 mg.g-1 for Sb(III) and Sb(V), respectively. The prepared Fe3O4 could be easily regenerated and reused for adsorption/desorption studies multiple times without compromising the Sb adsorption ability. Further exploration indicated that the oxidation or reduction reactions infrequently occurred during Sb adsorption processes. The proposed hierarchically nanostructured Fe3O4 thus could be potentially used for sustainable and efficient antimony removal.
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Antimônio , Poluentes Químicos da Água , Antimônio/química , Compostos Férricos/química , Adsorção , Micro-Ondas , OxirreduçãoRESUMO
Using filamentous fungi to capture unicellular microalgae is an effective way for microalgae recovery in water treatment. Here, fungi Aspergillus flavus ZJ-1 and microalgae Chlorella vulgaris WZ-1 isolated from a copper tailings pond were used to study the capture effect of ZJ-1 on WZ-1. The highest capture efficiency (97.85%) was obtained within 6 h under the optimized conditions of 30 °C, 150 rpm, fungi-algae biomass ratio of 2.24:1, and initial pH of 9.24 in microalgae medium. The formed fungi-algae pellets (FAPs) were further used to remove Cu(II) from aqueous solution. Results showed that the FAPs formed at different capture times all adsorbed Cu(II) well, and the PAFs formed within 2 h (PAFs2 h) exhibited the highest Cu(II) adsorption capacity (80.42 mg·g-1). SEM images showed that Cu(II) caused a change in the internal structure of PAFs2 h from loose to compact, the mycelium shrunk, and the microalgal cells were concave. Cu(II) adsorption by PAFs2 h was well conformed to the pseudo-second-order kinetics and the Langmuir isotherm (123.61 mg·g-1 of theoretically maximum adsorption capacity). This work opens a way for applying FAPs in the remediation of heavy metal-contaminated wastewater, and the metal adsorption effect was determined by the capture amount of microalgae.
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Chlorella vulgaris , Microalgas , Poluentes Químicos da Água , Adsorção , Aspergillus flavus , Cobre , Águas Residuárias , Cinética , Fungos , Concentração de Íons de Hidrogênio , Poluentes Químicos da Água/químicaRESUMO
RATIONALE AND OBJECTIVES: To evaluate whether the dual-layer spectral computed tomography urography (DL-CTU) images could predict WHO/ISUP pathological grading of clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We retrospectively included patients (n = 50) with pathologically confirmed ccRCC who underwent preoperative DL-CTU (from October 2017 to February 2021). They were divided into low-grade (WHO/ISUP 1/2, n = 30) and high-grade groups (WHO/ISUP 3/4, n = 20). The lesion size, attenuation (HU), iodine concentration (IC), normalized IC(NIC), and other quantitative characteristics were compared between the two groups. HU, IC, and NIC were obtained by plotting ROI with two different methods (circular ROI in the solid component or irregular ROI along the tumor edge containing tumor necrotic components). Receiver operating characteristic curves and multivariable model were used to evaluate the ability of parameters to predict WHO/ISUP grade. RESULTS: Transverse diameter (TD) of low-grade tumors was smaller, and HU in the non-contrast phase of the second method (HU-U-2) was lower than that of high-grade tumors (34.21±15.14 mm vs. 46.50 ± 20.68 mm, 27.33 ± 6.65 HU vs. 31.36 ± 6.09 HU, p< 0.05). The NIC in the nephrographic phase by the two methods (NIC-N-1 and NIC-N-2) of low-grade was higher than that of the high-grade group (0.78± 0.19 vs.0.58 ± 0.22, 0.73 ± 0.42 vs. 0.46 ± 0.22, p< 0.05). The final multivariable model composed of TD, HU-U-2, and NIC-N-1 could predict ccRCC grade with the area under the curve, sensitivity, specificity, and accuracy of 0.852, 70%, 90%, and 82%. CONCLUSION: Quantitative indicators in DL-CTU images could help predict the WHO/ISUP grade of ccRCC.
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Carcinoma de Células Renais , Iodo , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Organização Mundial da Saúde , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Gradação de TumoresRESUMO
Four series of forty-five nitrogen-containing polyhydroxylated aromatics based on caffeic acid phenethyl ester were designed and synthesized as HIV-1 integrase (IN) inhibitors. Most of these compounds inhibited IN catalytic activities in low micromolar range. Among these new analogues, compounds 9e and 9f were the most potent IN inhibitors with IC(50) value of 0.7 µM against strand transfer reaction. Their key structure-activity relationships were also discussed.
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Inibidores de Integrase de HIV/química , Inibidores de Integrase de HIV/farmacologia , Nitrogênio/análise , Compostos Policíclicos/química , Compostos Policíclicos/farmacologia , Linhagem Celular , HIV/efeitos dos fármacos , HIV/fisiologia , Inibidores de Integrase de HIV/síntese química , Humanos , Hidroxilação , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Compostos Policíclicos/síntese química , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacosRESUMO
Myocardial ischemia/reperfusion (MI/RI) syndrome is one of the leading causes of mortality and disability. Propofol postconditioning is known to improve myocardial ischemia/reperfusion injury (MI/RI). The present study aimed to explore the mechanism of propofol postconditioning in diabetic MI/RI. Diabetic MI/RI rat models were established and the rats were treated via propofol postconditioning. Staining with 2,3,5triphenyl2Htetrazolium chloride, H&E staining, TUNEL staining and ELISA were applied to detect infarct size, pathological changes, apoptosis and oxidative stressrelated factor and apoptotic factor levels, respectively. Subsequently, the effect of propofol on H9C2 cells was also assessed using the Cell Counting Kit8 assay. Highglucose hypoxia/reperfusion (H/R) models of H9C2 cardiomyocytes were established. miR200c3p overexpression or AdipoR2 silencing combined with propofol postconditioning was performed in H/Rinduced H9C2 cells and STAT3 protein expression levels were determined. Propofol postconditioning significantly reduced myocardial infarct size, oxidative stress and apoptosis in diabetic MI/RI models. Furthermore, propofol postconditioning significantly reduced the oxidative stress and apoptosis of H9C2 cells in highglucose H/R models. Propofol postconditioning also significantly downregulated miR200c3p expression levels and promoted AdipoR2 expression levels. miR200c3p overexpression or AdipoR2 downregulation significantly reversed the effects of propofol postconditioning on its antioxidation and antiapoptotic effects in H9C2 cells and on decreasing STAT3 phosphorylation levels. Together, the results of the present study demonstrated that propofol postconditioning inhibited miR200c3p, upregulated AdipoR2 and activated the STAT3 signaling pathway, thus alleviating diabetic MI/RI and therefore highlighting its potential as a treatment of diabetic MI/RI.
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Diabetes Mellitus , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Propofol , Animais , Apoptose , Diabetes Mellitus/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Propofol/farmacologia , Propofol/uso terapêutico , Ratos , Transdução de SinaisRESUMO
BACKGROUND: Some studies have found that heart-type fatty acid-binding protein (H-FABP) is related to the prognosis of patients with sepsis. This study aimed to explore whether H-FABP could predict the 28-day mortality in patients with sepsis. METHODS: Seven databases were searched, and the studies were screened based on the inclusion and exclusion criteria to assess the quality. The pooled sensitivity (SEN), specificity (SPE) positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve were calculated along with the 95% confidence interval (CI) values. Deeks' funnel plot was used to ascertain any publication bias. Meta-regression analysis was performed to explore the possible sources of heterogeneity. RESULTS: Seven studies were assessed that included 822 patients with sepsis. The pooled SEN was 0.76 (95% CI, 0.71-0.81), SPE was 0.66 (95% CI, 0.61-0.70), PLR was 2.21 (95% CI, 1.73-2.83), NLR was 0.36 (95% CI, 0.29-0.54), DOR was 6.23 (95% CI, 4.27-9.11) and the pooled AUC was 0.8137. There was no publication bias. Race, literature language, sampling time, threshold division and threshold effect were not the causes for the large heterogeneity. CONCLUSIONS: This meta-analysis suggests that H-FABP has high accuracy in predicting the 28-day mortality rate of patients with sepsis.
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Sepse , Área Sob a Curva , Biomarcadores/metabolismo , Proteína 3 Ligante de Ácido Graxo , Humanos , Curva ROC , Sepse/diagnóstico , Sepse/etiologia , Sepse/metabolismoRESUMO
BACKGROUND: Renal cell carcinoma (RCC) is the most common renal malignant tumour. We evaluated the potential value and dose reduction of virtual non-contrast (VNC) images and virtual monoenergetic images (VMIs) from dual-layer spectral CT (DL-CT) in the diagnosis of RCC. RESULTS: Sixty-two patients with pathologically confirmed RCC who underwent contrast-enhanced DL-CT were retrospectively analysed. For the comparison between true non-contrast (TNC) and VNC images of the excretory phase, the attenuation, image noise, signal-to-noise ratio (SNR) and subjective image quality of tumours and different abdominal organs and tissues were evaluated. To compare corticomedullary phase images and low keV VMIs (40 to 100 keV) from the nephrographic phase, the attenuation, image noise, SNR and subjective lesion visibility of the tumours and renal arteries were evaluated. For the tumours, significant differences were not observed in attenuation, noise or SNR between TNC and VNC images (p > 0.05). For the abdominal organs and tissues, except for fat, the difference in attenuation was 100% within 15 HU and 96.78% within 10 HU. The subjective image quality of TNC and VNC images was equivalent (p > 0.05). The attenuation of lesions in 40 keV VMIs and renal arteries in 60 keV VMIs were similar to those in the corticomedullary images (p > 0.05). The subjective lesion visibility in low keV VMIs is slightly lower than that in the corticomedullary images (p < 0.05). Using VNC and VMIs instead of TNC and corticomedullary phase images could decrease the radiation dose by 50.5%. CONCLUSION: VNC images and VMIs acquired from DL-CT can maintain good image quality and decrease the radiation dose for diagnosis of RCC.
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The rapid development of greenhouse vegetable production (GVP) in densely populated areas may cause the heavy metal/metalloid accumulation in soil and pose a threat to human health. In this study, 180 pairs of topsoil and pak choi (Brassica chinensis L.) samples were collected from GVP fields in Xi'an city in Northwest China to analyze health risks of Cd, Cr, Pb, and As in soil and pak choi combining in vitro bioaccessibility investigation. The results showed that Cd and Cr were common pollutants in both soil and pak choi. In the soil-pak choi system, the indexes of non-carcinogenic and carcinogenic risk for adults and children were 1.53, 2.68, and 1.37â¯×â¯10-4, 8.14â¯×â¯10-5, respectively, thereby indicating the presence of heavy metal/metalloid health risks for both groups. Based on the results, procedures to mitigate heavy metal/metalloid contamination risks should be discussed more during the development of GVP in the largest city in Northwest China.
Assuntos
Brassica , Metaloides , Metais Pesados , Poluentes do Solo , Adulto , Criança , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Metais Pesados/toxicidade , Medição de Risco , Solo , Poluentes do Solo/análise , VerdurasRESUMO
RATIONALE AND OBJECTIVES: To explore the value of an artificial intelligence (AI)-based application for identifying plaque-specific stenosis and obstructive coronary artery disease from monoenergetic spectral reconstructions on coronary computed tomography angiography (CTA). MATERIALS AND METHODS: This retrospective study enrolled 71 consecutive patients (52 men, 19 women; 63.3 ± 10.7 years) who underwent coronary CTA and invasive coronary angiography for diagnosing coronary artery disease. The conventional 120 kVp images and eight different virtual monoenergetic images (VMIs) (from 40 keV to 140 keV at increment of 10 keV) were reconstructed. An AI system automatically detected plaques from the conventional 120 kVp images and VMIs and calculated the degree of stenosis, which was further compared to invasive coronary angiography. The assessment was performed at a segment, vessel, and patient level. RESULTS: Vessel and segment-based analyses showed comparable diagnostic performance between conventional CTA images and VMIs from 50 keV to 90 keV. For vessel-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of conventional CTA were 74.3% (95% CI: 64.9%-82.0%), 85.6% (95% CI: 77.0%-91.4%), 84.3% (95% CI: 75.2%-90.7%), 76.1% (95% CI: 67.1%-83.3%) and 79.8% (95% CI: 73.7%-84.9%), respectively; the average sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy values of the VMIs ranging from 50 keV to 90 keV were 71.6%, 90.7%, 87.5%, 64.1% and 81.6%, respectively. For plaque-based assessment, diagnostic performance of the average VMIs ranging from 50 keV to 100 keV showed no significant statistical difference in diagnostic accuracy compared to those of conventional CTA images in detecting calcified (91.4% vs. 93.8%, p > 0.05), noncalcified (92.6% vs. 85.2%, p > 0.05) or mixed (80.2% vs. 81.2%, p > 0.05) stenosis, although the specificity was slightly higher (53.4% vs. 40.0%, p > 0.05) in detecting stenosis caused by mixed plaques. For VMIs above 100 keV, the diagnostic accuracy dropped significantly. CONCLUSION: Our study showed that the performance of an AI-based application employed to detect significant coronary stenosis in virtual monoenergetic reconstructions ranging from 50 keV to 90 keV was comparable to conventional 120 kVp reconstructions.