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Wireless sensor network (WSN) underpinning the smart-grid Internet of Things (SG-IoT) has been a popular research topic in recent years due to its great potential for enabling a wide range of important applications. However, the energy consumption (EC) characteristic of sensor nodes is a key factor that affects the operational performance (e.g., lifetime of sensors) and the total cost of ownership of WSNs. In this paper, to find the modulation techniques suitable for WSNs, we investigate the EC characteristic of continuous phase modulation (CPM), which is an attractive modulation scheme candidate for WSNs because of its constant envelope property. We first develop an EC model for the sensor nodes of WSNs by considering the circuits and a typical communication protocol that relies on automatic repeat request (ARQ)-based retransmissions to ensure successful data delivery. Then, we use this model to analyze the EC characteristic of CPM under various configurations of modulation parameters. Furthermore, we compare the EC characteristic of CPM with that of other representative modulation schemes, such as offset quadrature phase-shift keying (OQPSK) and quadrature amplitude modulation (QAM), which are commonly used in communication protocols of WSNs. Our analysis and simulation results provide insights into the EC characteristics of multiple modulation schemes in the context of WSNs; thus, they are beneficial for designing energy-efficient SG-IoT in the beyond-5G (B5G) and the 6G era.
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Dysregulated miRNAs have been demonstrated to be associated with the progression of colon cancer. The dysregulation of miR-3133 was observed in colon cancer, but its specific function was unclear. The functional role of miR-3133 in colon cancer was investigated in this study. A total of 113 colon cancer patients were included. miR-3133 expression was evaluated by PCR. The biological effects of miR-3133 in colon cancer cells were assessed with the help of the transwell and CCK8 assay. The prognostic value of miR-3133 was estimated by a series of statistical analyses. In mechanism, the interaction between miR-3133 and RUFY3 was evaluated by luciferase reporter. The significant downregulation of miR-3133 was observed in colon cancer, which showed a significant association with the advanced TNM stage and bad survival of patients. miR-3133 and TNM stage were identified as independent prognostic indicators of colon cancer. In vitro, the overexpression of miR-3133 exerted a dramatically inhibitory effect on cellular processes of colon cancer, which were enhanced by miR-3133 knockdown. Additionally, miR-3133 could negatively regulate the luciferase activity and expression of RUFY3, which was speculated as the underlying mechanism mediating the regulatory effect of miR-3133. miR-3133 functioned as a prognostic biomarker indicating the progression and prognosis of colon cancer, and it also served as a tumor suppressor via negatively regulating RUFY3, which provides a potential therapeutic target for colon cancer.
Assuntos
Neoplasias do Colo , MicroRNAs , Humanos , Linhagem Celular Tumoral , MicroRNAs/genética , Regulação para Baixo , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas do Citoesqueleto/metabolismoRESUMO
BACKGROUND: Rectal foreign bodies (RFB) are quite uncommon except in very busy hospitals. Because of their rarity, it is seldom that the treating physicians have a standard approach to the diagnosis, technique of extraction, and post-extraction evaluation. This can be further complicated by the rather extreme variability of size, shape, and texture of the foreign bodies, as well as the potential extent of trauma to the rectum or distal colon. AIM: The objectives of this study were to delineate the demographics, classification of cause, and injury patterns of RFB and to present the results of the transanal surgical management of a large series of RFB. METHODS: We retrospectively collected extensive data from the hospital medical records of the 291 patients who presented with RFB to the emergency department of Shenyang Proctological Hospital (Shenyang, China) from 2012 July to 2020 December. Specifically, demographics, origins and circumstance of the RFB, complications, injuries, anesthesia method, and the results of the transanal surgical management were recorded and analyzed. RESULTS: Of the 291 RFB cases, 225 (77.3%) were male and 66 (22.7%) were female, with a mean age of 53.8 ± 15.5 years (range, 1 ~ 88 years). The circumstances of the RFB were categorized as swallowed, 199 cases (68.4%); self-inserted, 87 (29.9%); and iatrogenic, 5 (1.7%). The proportion of males in the self-inserted RFB group was significantly greater than the swallowed RFB group (t = 31.114, p = 0.000). In the swallowed RFB group, the most common anorectal injuries and pathological changes were the following: penetration into the mucosa (75 cases, 37.7%), perianal or submucosal abscess (27 cases, 13.6%), and penetration into the anal canal (18 cases, 9.0%). In the self-inserted RFB group, 64 (73.6%) of the 87 cases had an intact rectum, whereas 8 (9.2%) had rectal mucosal ulcers and bleeding, and 7 (8%) had rectal lacerations. In the iatrogenic RFB group, 3 cases (60%) had rectal mucosal ulcers and bleeding, and 2 cases (40%) had inflammation of the rectal mucosa. Regarding extraction procedures, in the swallowed group, 187(187/199; 94%) patients underwent a transanal surgical procedure, and all were successful. In the self-inserted group, 82 patients underwent the transanal surgical procedure, and 74 (74/82; 90.2%) were successful whereas it was unsuccessful in the remaining 8 patients (8/82, 9.8%). Three (3/4, 75%) patients with iatrogenic RFB were resolved by the transanal surgical procedure. CONCLUSION: Men were markedly more likely than women to have swallowed RFBs and self-inserted RFBs. No serious damage to the rectum and anus was found in cases of swallowed RFB. Moreover, most surgical operations to remove foreign bodies via the anus were successful in this category of RFB. In contrast, rectal injury was more severe in patients with self-inserted RFB, such as rectal laceration, rectal mucosal ulcer, and bleeding. Moreover, the transanal removal operation in patients with self-inserted RFB had a failure rate of nearly 10%. Thick, long, hard foreign bodies did present a great challenge to the operator. Therefore, if necessary, patients with foreign bodies may need to be promptly referred for transabdominal removal.
Assuntos
Corpos Estranhos , Úlcera , Adulto , Idoso , Feminino , Corpos Estranhos/complicações , Corpos Estranhos/cirurgia , Humanos , Doença Iatrogênica , Masculino , Pessoa de Meia-Idade , Reto/cirurgia , Estudos Retrospectivos , Úlcera/complicaçõesRESUMO
Phosphates are the dominant phosphorus (P) source on Earth. The phosphates govern available P in soil, or even the complete ecosystem. The common deficiency of available P in carbonate-enriched soils suggests the tight correlation between P and C biogeochemistry, although the two elements have diverse abundance in soil. The influences of carbonates on P cycle were reviewed in this study, via both abiotic and biotic pathways. The abiotic processes at geochemical scale include element release, transport, sorption, desorption, weathering, precipitation, etc. The sorption of P on carbonate and buffering ability of carbonates were particularly addressed. Biotic factors are ascribed to various microorganisms in soil. As the most active P pool in soil, microorganisms prefer to consume abundant P, and then accumulate it in their biomass. Carbonates, however, are usually utilized by microorganisms after conversion to organic C. Meanwhile, extracellular precipitation of Ca-P phases significantly regulates the transportation of P in/out the cells. Moreover, they boost and complexify both carbonates and P turnover in soil via bioweathering and biomineralization, i.e., the intense interactions between biosphere and lithosphere. Based on this review, we proposed that carbonates may negatively affect P supply in soil system. This comprehensive review regarding the regulation by carbonates on P biogeochemistry would shed a light on predicting long-term P availability influenced by C biogeochemistry.
Assuntos
Fósforo , Solo , Carbonatos , Ecossistema , Fosfatos , Solo/químicaRESUMO
Soil is a main source of fluoride for plants. The tea plants (Camellia sinensis) accumulate excessive amounts of fluoride in their leaves compared to other plants, but their fluoride tolerance mechanism is poorly understood. A chloroplast fluoride efflux gene (CsABCB9) was newly discovered by using transcriptome analysis, cloned from Camellia sinensis, and its function was demonstrated in the fluoride detoxication mechanism in Escherichia coli/Xenopus laevis oocytes and Arabidopsis thaliana. CsABCB9 is expressed in tea leaves upon F− treatment. The growth of tea, E. coli, and Arabidopsis were inhibited by F− treatment. However, growth of CsABCB9-overexpression in E. coli was shown to increase with lower fluoride content under F− treatment compared to the control. Furthermore, chlorophyll, xanthophyll and soluble sugar contents of CsABCB9-overexpression in Arabidopsis were improved under F− treatment compared to the wild type. CsABCB9 functions in fluoride transport, and the mechanism by which CsABCB9 improves fluoride resistance in tea is mainly chloroplast protection through fluoride efflux.
Assuntos
Arabidopsis , Camellia sinensis , Arabidopsis/genética , Camellia sinensis/genética , Cloroplastos/genética , Escherichia coli/genética , Fluoretos/farmacologia , Folhas de Planta/genética , CháRESUMO
Hepatocellular carcinoma (HCC), one of the most lethal malignancies worldwide, has limited efficient therapeutic options. Here, we first demonstrated that simultaneously targeting poly (ADP-ribose) polymerase (PARP) and autophagy could evoke striking synergistic lethality in HCC cells. Specifically, we found that the PARP inhibitor Niraparib induced cytotoxicity accompanied by significant autophagy formation and autophagic flux in HCC cells. Further experiments showed that Niraparib induced suppression of the Akt/mTOR pathway and activation of the Erk1/2 cascade, two typical signaling pathways related to autophagy. In addition, the accumulation of reactive oxygen species was triggered, which was involved in Niraparib-induced autophagy. Blocking autophagy by chloroquine (CQ) in combination with Niraparib further enhanced cytotoxicity, induced apoptosis and inhibited colony formation in HCC cells. Synergistic inhibition was also observed in Huh7 xenografts in vivo. Mechanistically, we showed that autophagy inhibition abrogated Niraparib-induced cell-cycle arrest and checkpoint activation. Cotreatment with CQ and Niraparib promoted the formation of γ-H2AX foci while inhibiting the recruitment of the homologous recombination repair protein RAD51 to double-strand break sites. Thus, the present study developed a novel promising strategy for the management of HCC in the clinic and highlighted a potential approach to expand the application of PARP inhibitors.
Assuntos
Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Cloroquina/farmacologia , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Histonas/genética , Humanos , Indazóis/farmacologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Proteína Oncogênica v-akt/genética , Piperidinas/farmacologia , Poli(ADP-Ribose) Polimerases/genética , Serina-Treonina Quinases TOR/genéticaRESUMO
Purpose: To optimize treatment schemes using 2450-MHz microwave ablation (MWA), a novel conformal coverage method based on bipolar-angle mapping is proposed that determines whether a liver tumor is completely encompassed by thermal coagulation zones. Materials and methods: Firstly, three-dimensional (3-D) triangular mesh data of liver tumors were reconstructed from clinical computed tomography (CT) slices using the Marching cubes (MC) algorithm. Secondly, characterization models of thermal coagulation zones were established based on finite element simulation results of 40, 45, 50, 55, and 60 W ablations. Finally, coagulation zone models and tumor surface data were mapped and fused on a two-dimensional (2-D) plane to achieve conformal coverage of liver tumors by comparing the corresponding polar radii. Results: Optimal parameters for ablation treatment of liver tumors were efficiently obtained with the proposed conformal coverage method. Fifteen liver tumors were obtained with maximal diameters of 12.329-78.612 mm (mean ± standard deviation, 39.094 ± 19.447 mm). The insertion positions and orientations of the MWA antenna were determined based on 3-D reconstruction results of these tumors. The ablation patterns and durations of tumors were planned according to the minimum mean standard deviations between the ablative margin and tumor surface. Conclusion: The proposed method can be applied to computer-assisted MWA treatment planning of liver tumors, and is expected to guide clinical procedures in future.
Assuntos
Técnicas de Ablação/métodos , Eletrocoagulação/métodos , Neoplasias Hepáticas/cirurgia , Fígado/patologia , Humanos , Neoplasias Hepáticas/patologiaRESUMO
The soil cadmium (Cd) availability and uptake by Tagetes patula grown in two soil types contaminated with Cd and amended with N fertilizer and wheat straw were studied in a pot-culture experiment. The results indicated that N fertilizer treatment (N) and N fertilizer plus straw treatment (NS) promoted T. patula growth, while straw treatment (S) decreased T. patula biomass relative to the control. NS and S treatments increased Cd mobility in the soil and facilitated its uptake by T. patula in Acidic Ferralsols (AF) and Calcaric Cambisols (CC), but the promotion effect was much greater in CC than in AF. The Cd concentrations in the Tagetes shoots in the S and NS treatments were 40% and 27% greater, respectively, than those in the control treatment for AF, and 111% and 80% greater, respectively, for CC. Decreases in soil pH and increases in dissoluble organic carbon concentration after adding N fertilizer and straw were associated with an increase in soil Cd availability and in Cd uptake by T. patula. The results indicate that the NS treatment can alter the soil microenvironment, increasing Cd bioavailability and thus facilitating Cd uptake by T. patula. This work highlights that the combined application of N fertilizer with straw may be a useful way to increase the phytoextraction efficiency of Cd-contaminated soil by the Cd-hyperaccumulator T. patula.
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Cádmio/isolamento & purificação , Fertilizantes/análise , Nitrogênio/análise , Tagetes/metabolismo , Triticum , Concentração de Íons de Hidrogênio , Raízes de Plantas/metabolismo , Caules de Planta , Solo/química , Poluentes do Solo/isolamento & purificaçãoRESUMO
We proposed the deprotection-induced block copolymer self-assembly (DISA); that is, the deprotection of hydroxyl groups resulted in in situ self-assembly of glycopolymers. In the previous studies, block copolymers soluble in common organic solvents were employed as the starting material. In this paper, by using the protected glyco-block containing preassembled glycovesicles in water as the starting material, we moved forward and made two exceeding achievements. First, we have observed a deprotection-induced morphology transition triggered by alkali in water. The carbohydrate-carbohydrate interactions were considered to contribute to such a morphology transition during deprotection. Second, lipase was found to be an efficient enzymatic trigger in the sugar deprotection, which motivates the immune-application of this morphology transition process. When lipase and a model antigen, ovalbumin (OVA), were encapsulated inside the glycovesicles, the deprotection of sugars by lipase induced the transition of vesicles to micelles and the lipase and OVA were released accordingly. When glycovesicles were internalized by dentritic cells (DCs), the lipase from lysosomes efficiently induced the release of OVA and presentation of antigen to T cells. During the process, lysosomal lipase performed as a trigger on the deprotection of sugars and the release of protein without any other reagents. The significance of this design is that as a delivery vehicle, the protected glycovesicles not only avoided unnecessary immune activation but also worked with the released OVA together; that is, the glycovehicle successfully activated DCs and improved the presentation efficiency of T cells remarkably.
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Preparações de Ação Retardada/química , Lipase/administração & dosagem , Ovalbumina/administração & dosagem , Polietilenoglicóis/química , Poliestirenos/química , Açúcares/química , Animais , Apresentação de Antígeno , Linhagem Celular , Células Dendríticas/imunologia , Lipase/química , Camundongos , Micelas , Modelos Moleculares , Ovalbumina/química , Ovalbumina/imunologia , Triticum/enzimologiaRESUMO
Combinations of remediation technologies are needed to solve the problem of soil contamination in paddy rice, due to multiple potential toxic elements (PTEs). Two potential mitigation methods, water management and in-situ remediation by soil amendment, have been widely used in treatment of PTE-polluted paddy soil. However, the interactive relationship between soil amendment and water management, and its influence on the accumulation of PTEs in rice are poorly understood. Greenhouse pot experiments were conducted to examine the effects of phosphate amendment on Cd and Pb availability in soil and their influence on Cd and Pb uptake into rice, on Fe and P availability in soil, and on the alteration of Fe amount and compartment on root surface among different water management strategies. Results indicated that Cd and Pb content in the shoot and grain were significantly affected by the different water management strategies in nonamended soils, and followed the order: wetting irrigation > conventional irrigation > continuous flooding. The application of phosphate amendment significantly decreased the variations of Cd and Pb absorption in shoot and grain of rice among different water treatments. The reasons may be attributed to the enhancement of P availability and the decrease of Fe availability in soil, and the decreased variations of Fe2+/Fe3+ content in root coating after the application of phosphate amendment. These results suggested that the simultaneous use of phosphate amendment and continuous flooding to immobilize Cd and Pb, especially in acid paddy soils, should be avoided.
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Irrigação Agrícola/métodos , Cádmio/análise , Recuperação e Remediação Ambiental/métodos , Chumbo/análise , Oryza/química , Poluentes do Solo/análise , Solo/química , Ácidos , China , Grão Comestível/química , Poluição Ambiental/prevenção & controle , Concentração de Íons de Hidrogênio , Modelos Teóricos , Oryza/crescimento & desenvolvimento , Raízes de Plantas/químicaRESUMO
The interactions between plants and nanomaterials (NMs) can shed light on the environmental consequences of nanotechnology. We used the major crop plant rice (Oryza sativa L.) to investigate the uptake of gold nanoparticles (GNPs) coated with either negatively or positively charged ligands, over a 5-day period, in the absence or presence of one of two amino acids, aspartic acid (Asp) or lysine (Lys), acting as components of rice root exudates. The presence of Asp or Lys influenced the uptake and distribution of GNPs in rice, which depended on the electrical interaction between the coated GNPs and each amino acid. When the electrical charge of the amino acid was the same as that of the surface ligand coated onto the GNPs, the GNPs could disperse well in nutrient solution, resulting in increased uptake of GNPs into rice tissue. The opposite was true where the charge on the surface ligand was different from that on the amino acid, resulting in agglomeration and reduced Au uptake into rice tissue. The behavior of GNPs in the hydroponic nutrient solution was monitored in terms of agglomeration, particle size distribution, and surface charge in the presence and absence of Asp or Lys, which depended strongly on the electrostatic interaction. Results from this study indicated that the species of root exudates must be taken into account in assessing the bioavailability of nanomaterials to plants.
Assuntos
Ácido Aspártico/química , Ouro/metabolismo , Lisina/química , Nanopartículas Metálicas , Oryza/metabolismo , Transporte Biológico , Ligantes , Nanopartículas Metálicas/química , Tamanho da Partícula , Raízes de Plantas/metabolismoRESUMO
In this study Er³âº doped CaMoO4 (CaMoO4:Er³âº), and Er³âº/Yb³âº-co-doped CaMoO4 (CaMoO4:Er³âºYb³âº) nanoparticles have been synthesized by the microwave-assisted metathetic method. Er³âº/Yb³âº co-doped CaMoO4 nanoparticles sintered at 600 °C showed the strongest photoluminescence intensity, and crystallized well. At the excitation of 980 nm, the CaMoO4 nanoparticles show the strongest green emission at the 520 nm and 550 nm emission bands. Moreover, the green light produced has a better color purity.
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Cálcio/química , Érbio/química , Fluorescência , Micro-Ondas , Molibdênio/química , Itérbio/químicaRESUMO
Tea plant is known to be a hyper-accumulator of fluoride (F). Over-intake of F has been shown to have adverse effects on human health, e.g., dental fluorosis. Thus, understanding the mechanisms fluoride accumulation and developing potential approaches to decrease F uptake in tea plants might be beneficial for human health. In the present study, we found that pretreatment with the anion channel inhibitor NPPB reduced F accumulation in tea plants. Simultaneously, we observed that NPPB triggered Ca(2+) efflux from mature zone of tea root and significantly increased relative CaM in tea roots. Besides, pretreatment with the Ca(2+) chelator (EGTA) and CaM antagonists (CPZ and TFP) suppressed NPPB-elevated cytosolic Ca(2+) fluorescence intensity and CaM concentration in tea roots, respectively. Interestingly, NPPB-inhibited F accumulation was found to be significantly alleviated in tea plants pretreated with either Ca(2+) chelator (EGTA) or CaM antagonists (CPZ and TFP). In addition, NPPB significantly depolarized membrane potential transiently and we argue that the net Ca(2+) and H⺠efflux across the plasma membrane contributed to the restoration of membrane potential. Overall, our results suggest that regulation of Ca(2+)-CaM and plasma membrane potential depolarization are involved in NPPB-inhibited F accumulation in tea plants.
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Cálcio/metabolismo , Calmodulina/metabolismo , Camellia sinensis/efeitos dos fármacos , Fluoretos/metabolismo , Bombas de Íon/antagonistas & inibidores , Nitrobenzoatos/farmacologia , Proteínas de Plantas/metabolismo , Camellia sinensis/citologia , Camellia sinensis/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Raízes de Plantas/citologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismoRESUMO
Pien Tze Huang (PZH) is a well-known traditional Chinese formulation and has long been used as an alternative remedy for cancers in China and Southeast Asia. Recently, antitumor activity of PZH on several tumors have been increasingly reported, but its antitumor activity and the possible action mechanism on osteosarcoma remains unclear. After treatment with PZH, cell viability of MG-63 cells was dose-dependently inhibited compared to control cells. Moreover, a DNA ladder characteristic of apoptosis was observed in the cells treated with PZH, especially 500 µg/mL, 750 µg/mL. Further investigation showed that PZH treatments led to activation of caspase cascades and changes of apoptotic mediators Bcl2, Bax, and Bcl-xL expression. In addition, our results suggested that PZH activated PI3K/Akt signal pathway, and the phosphorylation of Akt and ERK1/2 were associated with the induction of apoptotic signaling. These results revealed that PZH possesses antitumoral activity on human osteosarcoma MG63 cells by manipulating apoptotic signaling and multiple pathways. It is suggested that PZH alone or combined with regular antitumor drugs may be beneficial as osteosarcoma treatments.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Ósseas/metabolismo , Medicamentos de Ervas Chinesas/química , Metanol/farmacologia , Osteossarcoma/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Apoptose , Neoplasias Ósseas/tratamento farmacológico , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/farmacologia , Células HT29 , Humanos , Osteossarcoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
BACKGROUND: Generally, tea plants are grown in acid soil which is rich in aluminum (Al) and fluoride (F). A recent publication showed that pretreatment with Al(3+) promoted F accumulation in tea plants by increasing endogenous Ca(2+) and calmodulin (CaM). A high level of F in tea leaves not only impairs tea quality but also might pose a health risk for people drinking tea regularly. Therefore it is important to try to find some clues which might be beneficial in controlling F accumulation in tea plants grown in acid soil (Al(3+) ). RESULTS: It was found that diisothiocyanostilbene-2,2-disulfonic acid (DIDS) significantly reduced Al(3+) -promoted F accumulation in tea plants. Additionally, Al(3+) plus DIDS treatment stimulated significantly higher Ca(2+) efflux and decreased the CaM level in tea roots compared with Al(3+) treatment. Besides, significantly higher depolarization of membrane potential was shown in tea roots treated with Al(3+) plus DIDS than in those treated with Al(3+) , as well as higher net total H(+) efflux and plasma membrane H(+) -ATPase activity. CONCLUSION: Al(3+) -promoted F accumulation in tea plants was inhibited by an anion channel inhibitor DIDS. Ca(2+) /CaM and membrane potential depolarization may be the components involved in this process. © 2016 Society of Chemical Industry.
Assuntos
Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia , Alumínio/farmacologia , Camellia sinensis/efeitos dos fármacos , Camellia sinensis/metabolismo , Fluoretos/farmacocinética , Adenosina Trifosfatases/metabolismo , Alumínio/química , Cálcio/metabolismo , Calmodulina/metabolismo , Camellia sinensis/química , Cátions/química , Cátions/farmacologia , Membrana Celular/metabolismo , Fluoretos/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Solo/químicaRESUMO
Acanthamoeba sp. parasites are the causative agents of Acanthamoeba keratitis, fatal granulomatous amoebic encephalitis, and cutaneous infections. However, there are currently no effective drugs for these organisms. Here, we evaluated the activity of the antimalarial agent artemether against Acanthamoeba castellanii trophozoites and identified potential targets of this agent through a proteomic approach. Artemether exhibited in vitro amoebicidal activity in a time- and dose-dependent manner and induced ultrastructural modification and cell apoptosis. The iTRAQ quantitative proteomic analysis identified 707 proteins that were differentially expressed after artemether treatment. We focused on phosphoglycerate dehydrogenase and phosphoserine aminotransferase in the serine biosynthesis pathway because of their importance to the growth and proliferation of protozoan and cancer cells. The expression of these proteins in Acanthamoeba was validated using quantitative real-time PCR and Western blotting after artemether treatment. The changes in the expression levels of phosphoserine aminotransferase were consistent with those of phosphoglycerate dehydrogenase. Therefore, the downregulation of phosphoserine aminotransferase may be due to the downregulation of phosphoglycerate dehydrogenase. Furthermore, exogenous serine might antagonize the activity of artemether against Acanthamoeba trophozoites. These results indicate that the serine biosynthesis pathway is important to amoeba survival and that targeting these enzymes would improve the treatment of Acanthamoeba infections. Artemether may be used as a phosphoglycerate dehydrogenase inhibitor to control or block Acanthamoeba infections.
Assuntos
Acanthamoeba castellanii/efeitos dos fármacos , Amebicidas/farmacologia , Antimaláricos/farmacologia , Artemisininas/farmacologia , Vias Biossintéticas/efeitos dos fármacos , Serina/metabolismo , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/metabolismo , Ceratite por Acanthamoeba/parasitologia , Acanthamoeba castellanii/metabolismo , Amebíase/tratamento farmacológico , Amebíase/metabolismo , Amebíase/parasitologia , Animais , Apoptose/efeitos dos fármacos , Artemeter , Proliferação de Células/efeitos dos fármacos , Encefalite/tratamento farmacológico , Encefalite/metabolismo , Encefalite/parasitologia , Fosfoglicerato Desidrogenase/metabolismo , Proteômica/métodos , Transaminases/metabolismo , Trofozoítos/parasitologiaRESUMO
AIM: To study the roles of autophagy in muscle establishment during long-term exercise in mice. METHODS: Female ICR mice were submitted to exercise training with a wheel running regimen: 6 m/min, 15 min/time, 3 times/d (on 8:00, 14:00, and 20:00), 5 d/week for 2 months. The mice were treated with the autophagy activator trehalose (1% aqueous solution as a daily drinking water) or the autophagy inhibitor chloroquine (10 mg/kg, ip, 5 times a week) before the training. Western blotting analysis, TUNEL staining, H&E staining and transmission electron microscope were used to evaluate the activity of autophagy and the structure of the muscle fibers. RESULTS: The exercise training significantly stimulated the formation of autophagosomes, increased the LC3-II, cathepsin L and Bcl-2 levels, lowered the P62 level and increased the antioxidant capacity in the muscles. Meanwhile, the exercise training significantly improved the morphology of mitochondria, reduced the release of cytochrome c from mitochondria to cytoplasm, and slightly decreased the apoptosis rate in the muscles. Administration of trehalose increased the level of autophagy and protected the muscle fibers from apoptosis. Administration of chloroquine blocked autophagy flux and exerted detrimental effects on the muscles, which were ameliorated by the exercise training. CONCLUSION: Long-term regular exercise activates autophagy process associated with muscle establishment, and ameliorates the detrimental effects of chloroquine on skeletal muscles via restoring autophagy flux.
Assuntos
Autofagia/fisiologia , Cloroquina/toxicidade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Condicionamento Físico Animal/fisiologia , Animais , Autofagia/efeitos dos fármacos , Feminino , Camundongos , Camundongos Endogâmicos ICR , Músculo Esquelético/efeitos dos fármacos , Condicionamento Físico Animal/métodos , Músculo Quadríceps/efeitos dos fármacos , Músculo Quadríceps/metabolismo , Músculo Quadríceps/patologiaRESUMO
Chronic myeloid leukemia (CML) is characterized by abnormal Bcr and Abl genes and enhanced tyrosine kinase activity. Anti-CML therapy has been much improved along with the applications of tyrosine kinase inhibitors (TKIs) which selectively target Bcr-Abl and have a cytotoxic effect on CML. Recently, four-membered heterocycles as "compact modules" have attracted much interest in drug discovery. Grafting these small four-membered heterocycles onto a molecular scaffold could probably provide compounds that retain notable activity and populate chemical space otherwise not previously accessed. Accordingly, a novel TKI, Thiotanib, has been designed and synthesized. It selectively targets Bcr-Abl, inducing growth inhibition, cell cycle arrest, and apoptosis of CML cells. Meanwhile, the compound Thiotanib could also induce autophagy in CML cells. Interestingly, inhibition of autophagy promotes Thiotanib-induced apoptosis with no further activation of caspase 3, while inhibition of caspases did not affect the cell survival of CML cells. Moreover, the compound Thiotanib could inhibit phosphorylation of Akt and mTOR, increase beclin-1 and Vps34, and block the formation of the Bcl-2 and Beclin-1 complex. This indicates the probable pathway of autophagy initiation. Our results highlight a new approach for TKI reforming and further provide an indication of the efficacy enhancement of TKIs in combination with autophagy inhibitors.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Inibidores Enzimáticos/síntese química , Humanos , Proteínas Proto-Oncogênicas c-abl/metabolismo , Proteínas Proto-Oncogênicas c-bcr/metabolismoRESUMO
Enterocytes die during high-dose radiation exposure in radiation accidents. The modality of cell death has a profound effect on the therapeutic response. The ilea from mice with 15 Gy total body irradiation (TBI) were drawn, morphological features observed by hematoxylin and eosin staining and transmission electron micrographs. The biochemical features of mouse ileum presented with the structure were cleaved Caspase-3 (apoptosis marker), Light Chain 3 (LC3)-I's conversion to LC3-II (autophagy marker) and high mobility group box chromosomal protein 1's secretion (necrosis marker). Then, the autophagy inhibitor (3-methyladenine), caspase inhibitor (Z-VAD-FMK) or necrosis inhibitor (necrostatin) was used to prevent death. Apoptosis, autophagy and necrosis were all appeared in the ileum, but necrosis had the biggest size; the use of 3-methyladenine and Z-VAD-FMK prolong one day's life of the mice after 15 Gy TBI, necrostatin significantly extended the lifespan of 15 Gy irradiated mice (p < 0.05). The results suggest that the death of enterocytes could not be classified into one type of cell death but rather as 'mixed death.'
Assuntos
Apoptose/efeitos da radiação , Autofagia/efeitos da radiação , Enterócitos/patologia , Intestinos/patologia , Adenina/análogos & derivados , Adenina/farmacologia , Adenina/uso terapêutico , Clorometilcetonas de Aminoácidos/farmacologia , Clorometilcetonas de Aminoácidos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Peso Corporal , Caspase 3/metabolismo , Inibidores de Caspase/farmacologia , Inibidores de Caspase/uso terapêutico , Enterócitos/efeitos dos fármacos , Enterócitos/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Fezes , Proteína HMGB1/metabolismo , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Indóis/farmacologia , Indóis/uso terapêutico , Mucosa Intestinal/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Necrose/tratamento farmacológico , Necrose/patologia , Doses de Radiação , Espécies Reativas de Oxigênio/metabolismo , Irradiação Corporal TotalRESUMO
Lightweight cryptography algorithms are a class of ciphers designed to protect data generated and transmitted by the Internet of Things. They typically have low requirements in terms of storage space and power consumption, and are well-suited for resource-limited application scenarios such as embedded systems, actuators, and sensors. The NIST-approved competition for lightweight cryptography aims to identify lightweight cryptographic algorithms that can serve as standards. Its objective is to enhance data security in various scenarios. Among the chosen standards for lightweight cryptography, ASCON has been selected. ASCON-HASH is a hash function within the ASCON family. This paper presents a detailed analysis of the differential characteristics of ASCON-HASH, utilizing the quadratic S-box. Additionally, we employ message modification techniques and ultimately demonstrate a non-practical collision attack on the 2-round ASCON-HASH, requiring a time complexity of 298 hash function calls.