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1.
J Med Virol ; 95(2): e28542, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36727647

RESUMO

The ongoing pandemic with the emergence of immune evasion potential and, particularly, the current omicron subvariants intensified the situation further. Although vaccines are available, the immune evasion capabilities of the recent variants demand further efficient therapeutic choices to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Hence, considering the necessity of the small molecule inhibitor, we target the main protease (3CLpro), which is an appealing target for the development of antiviral drugs against SARS-CoV-2. High-throughput molecular in silico screening of South African natural compounds database reported Isojacareubin and Glabranin as the potential inhibitors for the main protease. The calculated docking scores were reported to be -8.47 and -8.03 kcal/mol, respectively. Moreover, the structural dynamic assessment reported that Isojacareubin in complex with 3CLpro exhibit a more stable dynamic behavior than Glabranin. Inhibition assay indicated that Isojacareubin could inhibit SARS-CoV-2 3CLpro in a time- and dose-dependent manner, with half maximal inhibitory concentration values of 16.00 ± 1.35 µM (60 min incubation). Next, the covalent binding sites of Isojacareubin on SARS-CoV-2 3CLpro was identified by biomass spectrometry, which reported that Isojacareubin can covalently bind to thiols or Cysteine through Michael addition. To evaluate the inactivation potency of Isojacareubin, the inactivation kinetics was further investigated. The inactivation kinetic curves were plotted according to various concentrations with gradient-ascending incubation times. The KI value of Isojacareubin was determined as 30.71 µM, whereas the Kinact value was calculated as 0.054 min-1 . These results suggest that Isojacareubin is a covalent inhibitor of SARS-CoV-2 3CLpro .


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Proteases 3C de Coronavírus , Inibidores de Proteases/química , Simulação de Acoplamento Molecular , Antivirais/farmacologia
2.
Phys Chem Chem Phys ; 25(21): 14887-14897, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37199163

RESUMO

A.D. is a common disease among other neurodegenerative disorders primarily developing due to amyloid-ß (Aß) neurotoxicity derived from the amyloid-ß protein precursor (AßPP). The amyloid precursor-like proteins 1 and 2 (APP1 and APLP2) biochemically behave similarly in many aspects to AßPP. We, therefore, proposed to test WGX-50 and Alpha-M for their interaction mechanism with APLP1 and APLP2 because both these drug candidate compounds previously showed inhibition of Aß aggregation. We employed a comparative atomic investigation on Alpha-M and WGX-50 in complex with novel targets, i.e., APLP1 and APLP2, using biophysical and molecular simulation methods. The docking score was -6.83 kcal mol-1 for Alpha-M-APLP1, -8.41 kcal mol-1 for WGX-50-APLP1, -7.02 kcal mol-1 for Alpha-M-APLP2 and -8.25 kcal mol-1 for the WGX-50-APLP2 complex. Our results also elaborate that in the case of their interaction with both APLP1 and APLP2, the WGX-50 complex exhibits better stability than the APLP1/2-Alpha-M complexes during simulation. Furthermore, WGX50 in both APLP1 and APLP2 stabilized the internal flexibility upon binding in contrast to the Alpha-M complexes. The data showed that the BFE for Alpha-M-APLP1 was calculated to be -27.38 ± 0.93 kcal mol-1, for WGX-50-APLP1 -39.65 ± 0.95 kcal mol-1, for Alpha-M-APLP2 -24.80 ± 0.63 kcal mol-1 while for WGX-50-APLP2 the BFE was -57.16 ± 1.03 kcal mol-1 respectively. These results highlight that APLP2-WGX50 has greater binding energies in all four systems. PCA and FEL analysis further revealed variations in the dynamic behavior of these complexes. Overall, our findings demonstrate that WGX50 potentially acts as a more potent inhibitor for APLP1 and APLP2 than Alpha-M and thus shows the diverse pharmacological potential of WGX50. Due to its stable binding interaction, WGX50 might be a suitable candidate drug compound for targeting these precursors under pathological conditions.


Assuntos
Acrilamidas , Proteínas do Tecido Nervoso , Proteínas do Tecido Nervoso/metabolismo
3.
J Am Chem Soc ; 144(42): 19365-19371, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36227067

RESUMO

Growing attention has been paid to nanoclusters with face-centered cubic (fcc) metal kernels, due to its structural similarity to bulk metals. We demonstrate that the use of tetradentate formamidinate ligands facilitate the construction of two fcc silver nanoclusters: [Ag52(5-F-dpf)16Cl4](SbF6)2 (Ag52, 5-F-Hdpf = N,N'-di(5-fluoro-2-pyridinyl)formamidine) and [Ag53(5-Me-dpf)18](NO3)5 (Ag53, 5-Me-Hdpf = N,N'-di(5-methyl-2-pyridinyl)formamidine). Single-crystal X-ray structural analysis revealed that the silver atoms in both clusters are in a layer-by-layer arrangement, which can be viewed as a portion of the fcc packing of silver. The nitrogen donors of amidinate ligands selectively passivate the {111} facets. All silver atoms are involved in the fcc packing, that is, no staple motifs are observed due to the linear arrangement of the four N donors of the dpf ligands. The characteristic optical absorption bands of Ag52 and Ag53 have been studied with a time-dependent density functional theory. This work provides a facile access to assembling atomically precise fcc-type nanoclusters and shows the prospect of amidinates as protecting ligands in synthesizing metal nanoclusters.

4.
Neoplasma ; 68(2): 416-422, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33440991

RESUMO

The objective of this study was to investigate the expression of vesicular amine transporter 1 (VAT1) in hepatocellular carcinoma (HCC) and its prognostic value and to analyze the relationship between VAT1 expression and clinicopathological features of HCC. First, several public databases, including Ualcan, GEPIA, and Oncomine, were used to analyze the expression of VAT1 in HCC and normal liver tissue. Next, 330 HCC and 190 normal liver samples were stained by immunohistochemistry and scored. Finally, we evaluated the clinical significance of VAT1 as a prognostic factor according to the clinicopathological characteristics. We observed that the expression level of VAT1 in HCC samples was significantly higher than that in normal liver tissues, and the high expression of VAT1 protein in HCC was significantly correlated with patient age, tumor size, number of tumors, and vascular metastasis (p<0.05). The average survival time of HCC patients with high expression of VAT1 was significantly lower than that of patients with low expression of VAT1. Further analysis demonstrated that VAT1 expression was significantly correlated with the length of overall survival in HCC patients. In conclusion, VAT1 may have an essential function in the progression of HCC, and the level of its expression may effectively predict the invasion and prognosis of HCC. Moreover, the combination of information contained in public databases and the results of the analysis of clinical samples can help us to understand better the mechanism of action of molecular oncogenes in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Humanos , Imuno-Histoquímica , Prognóstico
5.
Lasers Med Sci ; 36(6): 1191-1200, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33044648

RESUMO

The benefit of transurethral laser prostatectomy over open simple prostatectomy (OSP) is controversial in aged symptomatic benign prostatic hyperplasia (BPH) patients with large volume prostates, and the aim of this study is to compare the safety and efficiency of these two methods. Meta-analysis was applied using the Review Manager V5.3 software and the retrieved randomized controlled clinical trials (RCTs) comparing transurethral laser prostatectomy with OSP were analyzed for the treatment of large volume prostates from 2000 to 2019 in PubMed, Web of Science, Cochrane, and EMBASE datasets. Five RCTs assessing transurethral laser prostatectomy versus OSP were considered suitable for this meta-analysis, which included a total of 448 patients, with 232 patients undergoing laser and 216 patients undergoing OSP. Compared with OSP, although transurethral laser prostatectomy required a longer operative time (weighted mean difference (WMD) 27.49 mins; 95% confidence interval (CI) 16.54-38.44; P < 0.00001) and obtained a less resected prostate weight (WMD - 11.72 g; 95% CI - 21.75 to - 1.70; P = 0.02), patients undergoing laser prostatectomy benefited from significantly less hemoglobin decline (- 0.97 g/dL; 95% CI - 1.31 to - 0.64; P < 0.00001), shorter time of catheterization (WMD - 3.67 days; 95% CI - 5.60 to - 1.75; P = 0.0002), shorter length of hospital stay (WMD - 4.75 days; 95% CI - 6.57 to - 2.93; P < 0.00001), and less blood transfusion (odds ratio 0.10; 95% CI 0.03 to 0.35; P = 0.0003). During postoperative follow-up, no significant difference was observed between the two groups in IPSS, QoL, Qmax, and PVR. Both transurethral laser prostatectomy and OSP are safe and effective for large prostates that require prostate resection. Taking into account of less blood loss, shorter catheterization time and hospital stay, and less blood transfusion, transurethral laser prostatectomy may be a better treatment for patients with large prostates.


Assuntos
Próstata/patologia , Próstata/cirurgia , Prostatectomia , Hiperplasia Prostática/patologia , Hiperplasia Prostática/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ressecção Transuretral da Próstata , Humanos , Masculino , Tamanho do Órgão
7.
J Hazard Mater ; 465: 133068, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38043422

RESUMO

Electroplating sludge (ES) is a globally prevalent hazardous waste that primarily contains Cr, Cu, Ni, and Fe. However, the residual Cr phases within the slag potentially poses an environmental risk in current vitrification. A novel method for effective recovering and solidifying Cr in ES is proposed in this work. ES was desulfurized and subsequently co-treated with ferrosilicon (Fe-Si) and spent carbon anode (SCA) for enhancing the recovery of Cr, Cu, Ni, and Fe to prepare crude stainless steel. Under optimal conditions, the recovery ratios of Cr, Cu, Ni, and Fe reached 96.96%, 99.45%, 99.92%, and 99.20%, respectively, signifying improvements of 21.4%, 0.2%, 1.5%, and 2.8%, respectively, compared with existing research. Meanwhile, the fluoride in SCA yielded CaF2, further progressing to the Si-Ca-F-Na-Al-O phase, with a solidification ratio of 97.87%. The Cr leaching content of the residual Cr-Cu-S phase in the slag remained below 5 mg/L across a pH range of 2-4, demonstrating enhanced stability compared to prior alloy, oxide, and chemically dissolved phases. An innovative approach for solidify Cr by forming matte holds implications for the treatment of Cr-containing solid wastes such as chromium slag, tannery sludge and stainless steel slag.

8.
J Plant Physiol ; 296: 154237, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583194

RESUMO

Selenium (Se) is an essential micronutrient for both human and animals. Plants serve as the primary source of Se in the food chain. Se concentration and availability in plants is influenced by soil properties and environmental conditions. Optimal Se levels promote plant growth and enhance stress tolerance, while excessive Se concentration can result in toxicity. Se enhances plants ROS scavenging ability by promoting antioxidant compound synthesis. The ability of Se to maintain redox balance depends upon ROS compounds, stress conditions and Se application rate. Furthermore, Se-dependent antioxidant compound synthesis is critically reliant on plant macro and micro nutritional status. As these nutrients are fundamental for different co-factors and amino acid synthesis. Additionally, phytohormones also interact with Se to promote plant growth. Hence, utilization of phytohormones and modified crop nutrition can improve Se-dependent crop growth and plant stress tolerance. This review aims to explore the assimilation of Se into plant proteins, its intricate effect on plant redox status, and the specific interactions between Se and phytohormones. Furthermore, we highlight the proposed physiological and genetic mechanisms underlying Se-mediated phytohormone-dependent plant growth modulation and identified research opportunities that could contribute to sustainable agricultural production in the future.


Assuntos
Antioxidantes , Selênio , Animais , Humanos , Antioxidantes/metabolismo , Selênio/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Plantas/metabolismo
9.
Gene ; 933: 148983, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39368788

RESUMO

The functions of major latex proteins (MLPs) in plant defense and stress responses have been widely documented; however, their roles in HT stress response in soybeans have not been elucidated. This study investigated the role of GmMLP34, a member of the major latex protein (MLP) family, in the response of soybeans to HT stress. Transcriptome analysis of HT-resistant (JD21) and HT-sensitive (HD14) soybean leaves under HT stress (43.40 ± 1.70 °C) and field conditions revealed differential expression of GmMLP34. Further examination across different HT-resistant varieties showed that GmMLP34 was down-regulated in the leaves of 6 HT-resistant varieties (85.7 %) and up-regulated in the leaves of 6 HT-sensitive varieties (85.7 %) under the HT treatment (45 °C for 3 h). The results of this study indicate that ectopic expression of the GmMLP34 gene in Arabidopsis led to a significant decrease in the survival rate of seedling when compared to the wild type (WT) under HT stress conditions of 37/28 °C (day/night) for 5 d, Moreover, the results indicated a significant decrease in primary root length and lateral root number under 45 °C/3 h HT stress followed by 12 h room temperature recovery. Additionally, the levels of abscisic acid (ABA), and flavonoids, and the activity of the peroxidase (POD) enzyme in the antioxidant system was decreased, while the activity of the superoxide dismutase (SOD) enzyme increased in GmMLP34-overexpressing transgenic Arabidopsis thaliana. The expression levels of the HT-response genes AtCHS1 and AtCHI2-A, were significantly down-regulated, whereas that of AtGBP1 was significantly up-regulated. These results suggest that GmMLP34 negatively regulates the response of Arabidopsis thaliana to HT stress by modulating flavonoid synthesis, hormone synthesis, and the antioxidant enzyme system. These findings provide theoretical information for the genetic improvement of HT tolerance in soybean and contribute to the understanding of the molecular mechanisms underlying plant responses to abiotic stress.

10.
Environ Sci Pollut Res Int ; 30(3): 7402-7414, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36040691

RESUMO

Through field surveys, sampling, and laboratory experiments, the content, enrichment, and migration characteristics of heavy metals in the rock-soil-tea system in the Guizhou metamorphic rock area were analyzed herein. The results show that the As and Hg contents in metamorphic sandstone in the study area are higher than those in slate, while the Mn, Zn, Pb, and Ni contents in slate are higher. The content of heavy metals in the sandstone of the Jialu formation of the Xiajiang group in Neoproterozoic is the highest, and that of the slate of the Fanzhao formation is the lowest. The content of As in the rock samples in the study area is higher than that in the Epicontinental crust, while Cd is found to be deficient. The heavy metals at some soil points exceed the standard, but this does not affect the growth and development of tea. The content of heavy metals in most tea is lower than the safety limit standards, and the THQ value is less than 1, indicating that the heavy metals in tea in Guizhou metamorphic rock areas pose no concern for human health. In the metamorphic rock distribution areas of Guizhou, tea does not enrich As, Cr, Hg, and Pb in soil, but enriches Mn, Cu, Ni, and Zn to varying degrees, with the enrichment of Mn being the strongest.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Humanos , Solo/química , Chumbo , Poluentes do Solo/análise , Monitoramento Ambiental , Medição de Risco , Metais Pesados/análise , China , Chá/química
11.
Cancer Med ; 12(19): 19968-19977, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37706606

RESUMO

BACKGROUND: The co-occurrence of depression and diabetes mellitus has been linked to an increased risk of developing cancer. This study aimed to investigate whether depression further amplifies the risk of cancer among individuals with diabetes. METHODS: This population-based matched cohort study utilized Taiwan's National Health Insurance claims database. A total of 85,489 newly diagnosed diabetic patients with depressive disorders were selected, along with 427,445 comparison subjects. The matching process involved age, sex, and the calendar year of diabetes onset. The average follow-up duration for the two cohorts was 6.4 and 6.5 years, respectively. The primary outcome of interest was the occurrence of overall cancer or cancer at specific anatomical sites. RESULTS: The adjusted hazard ratios for overall cancer incidence were 1.08 (95% CI, 1.05-1.11). For site-specific cancers, depression exhibited significant associations with oropharyngeal, esophageal, liver, gynecological, prostate, kidney, and hematologic malignancies among patients with diabetes. Notably, a severity-response relationship was observed, indicating that patients with recurrent episodes of major depressive disorders exhibited a higher incidence of cancer compared to those diagnosed with dysthymia or depressive disorder not otherwise specified. Furthermore, the strength of the association between depression and cancer risk was more pronounced among younger patients with diabetes as opposed to older adults. However, no significant relationship was observed between adherence to antidepressant treatment and cancer risk. CONCLUSIONS: The findings of this study indicate a significant association between depression and an elevated risk of cancer among individuals diagnosed with diabetes. Future investigations should replicate our findings, explore the effects of pharmacological and non-pharmacological treatments on cancer risk, and identify the underlying mechanisms.


Assuntos
Transtorno Depressivo Maior , Diabetes Mellitus , Neoplasias , Masculino , Humanos , Idoso , Estudos de Coortes , Depressão/complicações , Depressão/epidemiologia , Diabetes Mellitus/epidemiologia , Incidência , Neoplasias/epidemiologia , Fatores de Risco , Taiwan/epidemiologia
12.
Childs Nerv Syst ; 28(10): 1687-91, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22752120

RESUMO

OBJECTIVE: This study aims to evaluate effects and complications of the implantation of Ommaya reservoir in premature infants with posthemorrhagic hydrocephalus (PHH). METHODS: The effects and complications of the implantation of Ommaya reservoir in seven premature infants with PHH were retrospectively analyzed. Intracapsular puncture of the reservoir was performed for draining cerebrospinal fluid. RESULTS: Seven extremely low-weight premature infants with PHH (birthweight less than 1,000 g) were treated with the placement of an Ommaya reservoir. Ommaya reservoirs in five infants were removed, but were retained in two infants. Two premature infants had to undergo ventriculoperitoneal (VP) shunt. Postsurgical major complications (including skin dehiscence, cerebrospinal fluid (CSF) infection, ventricular hemorrhage, and CSF leak) occurred in 57% of all patients. Three infants of skin dehiscence and CSF leak occurred. Two infants of CSF infection occurred, as well as one clinically significant secondary hemorrhage. Six infants survived, and one died. CONCLUSION: The implantation of Ommaya reservoir is a cautious option of treating low-weight premature infants with PHH because of a relatively high complication rate. However, VP shunt surgery may be avoided in some infants.


Assuntos
Hemorragia Cerebral/complicações , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Lactente Extremamente Prematuro , Derivação Ventriculoperitoneal/efeitos adversos , Derivação Ventriculoperitoneal/instrumentação , Hemorragia Cerebral/líquido cefalorraquidiano , Feminino , Humanos , Hidrocefalia/líquido cefalorraquidiano , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
13.
Biomed Pharmacother ; 143: 112176, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34562770

RESUMO

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new variants reported in different countries have posed a serious threat to human health and social fabrics worldwide. In addition, these new variants hindered the efforts of vaccines and other therapeutic developments. In this review article, we explained the emergence of new variants of SARS-CoV-2, their transmission risk, mortality rate, and, more importantly, the impact of each new variant on the efficacy of the developed vaccines reported in different literature and findings. The literature reported that with the emergence of new variants, the efficacy of different vaccines is declined, hospitalization and the risk of reinfection is increased. The reports concluded that the emergence of a variant that entirely evades the immune response triggered by the vaccine is improbable. The emergence of new variants and reports of re-infections are creating a more distressing situation and therefore demands further investigation to formulate an effective therapeutic strategy.


Assuntos
Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/classificação , Vacinas contra COVID-19/farmacologia , Humanos , Imunogenicidade da Vacina , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Resultado do Tratamento
14.
Artigo em Inglês | MEDLINE | ID: mdl-33680066

RESUMO

PURPOSE: The aim of the research was to evaluate the efficacy and safety associated with Fuke Qianjin tablet combined with conventional therapy in the treatment of pelvic inflammatory diseases and associated complications (endometritis) using a meta-analysis approach. Patients and Methods. We searched 8 electronic databases up to December 31, 2019, including PubMed, the Cochrane Library, Embase, Web of Science, CNKI, WanFang, VIP, and SinoMed. Eligible studies were clinical trials of Fuke Qianjin tablet combined with conventional therapy used in the treatment of acute pelvic inflammatory disease, chronic pelvic inflammatory disease, and endometritis. The meta-analysis was performed using STATA15 software. RESULTS: A total of 125 RCTs (n = 14,494) were shortlisted for the meta-analysis, which included 23 trials for acute pelvic inflammatory disease, 69 trials for chronic pelvic inflammatory disease, and 33 trials for endometritis. The overall analysis illustrated Fuke Qianjin tablet combined with conventional therapy was significantly more efficacious than conventional therapy alone across all types of antibiotics treatment for acute pelvic inflammatory disease (OR = 5.57, 95% CI 4.09-7.58, Z = 10.90, p=0.001), chronic pelvic inflammatory disease (OR = 4.70, 95% CI 4.07-5.42, Z = 21.21, p=0.001) and endometritis (OR = 5.09, 95% CI 4.03-6.43; Z = 13.63, p=0.001) in both primary endpoints and secondary endpoints. There is also a trend that Fuke Qianjin tablet combined with conventional therapy has lower adverse reaction rates than conventional therapy alone. CONCLUSION: Fuke Qianjin tablet combined with conventional therapy showed better clinical efficacy in the treatment of acute pelvic inflammatory disease, chronic pelvic inflammatory disease, and endometritis. There were no obvious drug-related adverse reactions. Fuke Qianjin tablet presented advantages in shortening the remission time of clinical symptoms, reducing the concentration of serum inflammatory factors, improving endometrial thickness, menstruation, and reducing relapse rate.

15.
Chem Commun (Camb) ; 57(35): 4315-4318, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33913975

RESUMO

Copper hydrides are very useful in hydrogenation reactions. We report a stable Stryker-type copper hydride reagent protected by hemilabile phosphines: [Cu8H6(dppy)6](OTf)2 (Cu8-H, dppy = diphenylphosphino-2-pyridine). The metal core of this cluster has a bicapped octahedral configuration, and the copper-bound hydrides each triply bridges over a triangular face of the octahedron. This cluster is attractive due to its facile preparation and excellent stability under ambient conditions. The comparable activity and selectivity both in the stoichiometric and catalytic reactions make Cu8-H a promising alternative to Stryker's reagent.

16.
Curr Stem Cell Res Ther ; 15(5): 441-448, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995020

RESUMO

Recent interest in developing new regenerative medicine- and tissue engineering-based treatments has motivated researchers to develop strategies for manipulating stem cells to optimize outcomes in these potentially, game-changing treatments. Cells communicate with each other, and with their surrounding tissues and organs via electrochemical signals. These signals originate from ions passing back and forth through cell membranes and play a key role in regulating cell function during embryonic development, healing, and regeneration. To study the effects of electrical signals on cell function, investigators have exposed cells to exogenous electrical stimulation and have been able to increase, decrease and entirely block cell proliferation, differentiation, migration, alignment, and adherence to scaffold materials. In this review, we discuss research focused on the use of electrical stimulation to manipulate stem cell function with a focus on its incorporation in tissue engineering-based treatments.


Assuntos
Células-Tronco/citologia , Animais , Estimulação Elétrica , Humanos , Modelos Biológicos , Medicina Regenerativa , Transdução de Sinais , Engenharia Tecidual
17.
Interdiscip Sci ; 12(2): 155-168, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32056139

RESUMO

Breast cancer is the most common cause of death in women worldwide. Approximately 5%-10% of instances are attributed to mutations acquired from the parents. Therefore, it is highly recommended to design more potential drugs and drug targets to eradicate such complex diseases. Network-based gene expression profiling is a suggested tool for discovering drug targets by incorporating various factors such as disease states, intensities based on gene expression as well as protein-protein interactions. To find prospective biomarkers in breast cancer, we first identified differentially expressed genes (DEGs) statistical methods p-value and false discovery rate were initially used. Of the total 82 DEGs, 67 were upregulated while the remaining 17 were downregulated. Sub-modules and hub genes include VEGFA with the highest degree, followed by 15 CCND1 and CXCL8 with 12-degree score was found. The survival analysis revealed that all the hub genes have important role in the development and progression of breast cancer. Enrichment analysis revealed that most of these genes are involved in signaling pathways and in the extracellular spaces. We also identified transcription factors and kinases, which regulate proteins in the DEGs PPI. Finally, drugs for each hub genes were identified. These results further expanded the knowledge regarding important biomarkers in breast cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Biologia Computacional/métodos , Ciclina D1/genética , Ciclina D1/metabolismo , Descoberta de Drogas/métodos , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Modelos Biológicos , Fosfotransferases/genética , Fosfotransferases/metabolismo , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Transdução de Sinais , Análise de Sobrevida , Biologia de Sistemas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Leuk Res ; 75: 1-6, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30419548

RESUMO

Tyrosine kinase inhibitors have achieved unprecedented efficacy in the treatment of chronic myeloid leukemia (CML); however, imatinib resistance has emerged as a major problem in the clinic. Because the overexpression of BCR-ABL1 critically contributes to CML pathogenesis and drug resistance, targeting the regulation of BCR-ABL1 gene expression may be an alternative therapeutic strategy. In this study, we found that the transcriptional repressor MXD1 showed low expression in CML patients and was negatively correlated with BCR-ABL1. Overexpression of MXD1 markedly inhibited the proliferation of K562 cells and sensitized the imatinib-resistant K562/G01 cell line to imatinib, with decreased BCR-ABL1 mRNA and protein expression. Further investigation using reporter gene analysis showed that MXD1 significantly inhibited the transcriptional activity of the BCR-ABL1 gene promoter. Taken together, these data show that MXD1 functions as a negative regulator of BCR-ABL1 expression and subsequently inhibits proliferation and sensitizes CML cells to imatinib treatment.


Assuntos
Antineoplásicos/farmacologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Proteínas Repressoras/genética , Proteínas de Fusão bcr-abl/genética , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Células K562
19.
Ying Yong Sheng Tai Xue Bao ; 28(11): 3562-3570, 2017 Nov.
Artigo em Zh | MEDLINE | ID: mdl-29692099

RESUMO

Super hybrid early rice variety Ganxin 203 was used as test material, and four foliar spraying treatments were set using clear water as the control group (CK), and 3 concentrations of potassium dihydrogen phosphate (KH2PO4) with 0.1% (P1), 0.3% (P3), 0.5% (P5) and po-tash (MH). The effects of spraying P and K fertilizers on the leaf temperature, yield and physiolo-gical characteristics in double-season early rice under low temperature conditions during panicle primordium differentiation stage were studied. The results showed that during the low temperature period 6:00-18:00, rice leaf temperature under the different treatments with potassium dihydrogen phosphate and potash was higher than that of CK. Leaf chlorophyll content and net photosynthetic rate (Pn) of rice plants decreased gradually with the treatments under low temperature, while the reduction range was the smallest in treatment P3. The activities of the antioxidative enzymes varied to different extents, and the increase range for the activities of superoxide dismutase (SOD) and peroxidase (POD) in treatment P3 were higher than those in the other treatments. The decrease range of the activity catalase (CAT) in treatment P3 was lower than that in the other treatments. At the end of low temperature treatment, malondialdehyde (MDA) content was the highest in CK. Under low temperature, foliar spraying of potassium dihydrogen phosphate or potash could improve dry matter accumulation to varying degrees and achieve the purpose of slowing down the yield decrease, among which treatment P3 was the best. It could be found from the yield components that the total grains per panicle, seed setting rate and 1000-grain mass were significantly improved for all treatments compared to CK. The application of foliar spraying of 0.3% potassium dihydrogen phosphate was the most effective agronomic measure to enhance the resistance to low temperature during panicle primordium differentiation stage for double-season super hybrid early rice.


Assuntos
Fertilizantes , Oryza , Temperatura Baixa , Fotossíntese , Folhas de Planta
20.
Ying Yong Sheng Tai Xue Bao ; 28(12): 3935-3944, 2017 Dec.
Artigo em Zh | MEDLINE | ID: mdl-29696889

RESUMO

Taking super hybrid rice variety 'Wufengyou T025' as test material, the effects of different irrigation methods and water layer depth on physiological characteristics and yield in double-season late rice under low temperature conditions during heading and flowering stage were investigated. Three treatments were set, i.e., draining during day and containing 4-5 cm water layer during night (H1), draining during day and containing 8-10 cm water layer during night (H2), and containing 8-10 cm water layer day and night (H3), with the 0-1 cm water layer day and night was as the control (CK). The results showed that rice leaf temperature, soil layer temperature and canopy temperature under the different irrigation treatments were higher than that of CK, and the warming effect of treatment H2 was the best during the low temperature period. Leaf chlorophyll content, net photosynthetic rate, transpiration rate, leaf stomatal conductance and intercellular CO2 concentration of rice plants decreased gradually under the low temperature, while the smallest reduction occurred in H2. The increase ranges of malondialdehyde and proline content in H2 were lower, while its soluble protein content was the highest compared with other irrigation treatments. The increase ranges for the activities of superoxide dismutase and peroxidase in H2 were lower, while its decrease range for the activity of catalase was the lowest. Irrigation for heat preservation could increase the yield, and H2 performed best. Yield of H2 at the second sowing date in 2014 and 2015 encountering low temperature increased by 12.9% and 13.5% respectively compared to CK. The yield components including the effective panicle numbers per plant, panicle length, seed setting rate and 1000-grain mass were improved in all irrigation treatments compared to CK. Draining during day and containing 8-10 cm water layer during night (H2) was the most effective agronomic measure to enhance the tolerance to low temperature during heading and flowering stage for double-season hybrid late rice.


Assuntos
Temperatura Baixa , Oryza , Fotossíntese , Biomassa , Clorofila , Folhas de Planta , Água
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