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1.
Chemosphere ; 351: 141199, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38237785

RESUMEN

Glyphosate (N-(phosphonomethyl)glycine, GLY) ranks among the most extensively used and effective herbicides globally. However, excessive GLY utilization poses a substantial threat to the survival of honey bees (Apis cerana). Here we monitored the survival status of A. cerana treated with GLY, and conducted transcriptome sequencing of the bee gut and head to further explore potential GLY influences at the molecular level. We observed that the mortality rate of bees increased as GLY concentration escalated. Pivotal pathways emerged in response to the GLY treatment, with a substantial number of differentially expressed genes enriched in the longevity regulating pathway - multiple species. This strongly suggested that GLY may influence the physiological behavior of bees by impacting this particular pathway. Moreover, our analysis revealed a notable reduction in the enzymatic activities of CYP450 and AChE in both the bee head and intestines of when exposed to GLY. Conversely, the enzymatic activity of superoxide dismutase (SOD) in the head remained unaffected, whereas in the intestines, it exhibited a significant increase. Additionally, prophenol oxidase (PPO) and glutathione-S-transferases (GSTs) displayed contrasting trends in enzymatic activity in both organs. This study offers valuable insights into how GLY impacted the survival of A. cerana.


Asunto(s)
Glifosato , Herbicidas , Abejas , Animales , Longevidad , Glicina/toxicidad , Herbicidas/toxicidad
2.
Artículo en Inglés | MEDLINE | ID: mdl-37919894

RESUMEN

Background: Recent developments indicated that Bowman capsule rupture (BCR) is observed in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). We aimed to explore the relationship between BCR and clinical manifestations, pathological changes, and prognosis in children with myeloperoxidase (MPO)-AAGN. Methods: A total of 56 children with MPO-AAGN were divided into BCR (+) and BCR (-) groups according to the status of Bowman's capsule. Clinical and histological features and renal outcomes were compared, and the predictive value of BCR for end-stage kidney disease (ESKD) of MPO-AAGN was evaluated. Results: After retrospective analysis of the data, 24 children (42.9%) were found to have BCR. The results showed that BCR positively correlated with intrarenal immune cell infiltrates, obsolescence and crescents in glomeruli, tubulointerstitial inflammation, tubulitis, and tubular atrophy negatively correlated with normal glomeruli and immunoglobulin G deposition in the kidney. The clinical features and kidney pathological changes were more severe in the BCR (+) group than BCR (-) group, and the renal survival rate was significantly poorer in the BCR (+) group than BCR (-) group (χ2 = 5.45, p = 0.02). Moreover, estimated glomerular filtration rate (≤15 mL/min/1.73 m2), BCR and ANCA renal risk score (ARRS) were independent risk factors for the development of ESKD in children with MPO-AAGN. After combining BCR with the Berden classification and ARRS, our data suggested that the Berden classification + BCR and ARRS + BCR showed better predictive values for ESKD than those of the Berden classification and ARRS, respectively. Conclusion: BCR is an important pathological lesion that correlates with severe clinical manifestations, pathological changes, and poor prognosis in children with MPO-AAGN.

3.
Clin Case Rep ; 11(2): e05847, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36817312

RESUMEN

Left atrial appendage (LAA) is a finger-like muscular extension of the left atrium, and it is the most prominent site for cardiac thrombus in patients with atrial fibrillation. Congenital absence of LAA could be incidentally detected in patient with ischemic stroke and atrial fibrillation. Although it is considered to be an extremely rare cardiac anomaly, its clinical significance remains unknown and there is no clear consensus in the management strategy in those patients. Therefore, we report a case of an incidentally noted congenital absence of LAA in a 68-year-old woman being planned for LAA closure.

4.
Clin Neurol Neurosurg ; 223: 107496, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36334554

RESUMEN

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common and severe complication of acute herpes zoster. Early treatment of herpes zoster neuralgia is of great significance to reduce the incidence of PHN. This retrospective study evaluated the efficacy and safety of the combination of high-voltage pulsed radiofrequency (PRF) and oxygen-ozone(O2-O3) injection in patients with acute zoster neuralgia (AZN) who failed to respond to conservative treatment. METHODS: One-hundred patients diagnosed with AZN were classified into two groups (high-voltage PRF group [HP group, n = 50] and high-voltage PRF combined with O2-O3 injection group [HPO group, n = 50]) based on different treatment methods. Therapeutic effectiveness was assessed using a numerical rating scale (NRS) and the Pittsburgh Sleep Quality Index (PSQI). The dosages of gabapentin and tramadol (mg/d) before treatment and after 1 week and 1, 3, and 6 months of treatment were measured. The incidence of clinically meaningful PHN after treatment was also recorded. RESULTS: Pain intensity and sleep quality in both groups at all time points improved after treatment compared to before treatment (P < 0.05). After 1 week and 1 month of treatment, NRS and PSQI scores in both groups decreased, but the differences were not statistically significant (P > 0.05). NRS, PSQI scores, and the dosages of gabapentin and tramadol decreased more significantly in the HPO group than those in the HP group after 3 months (P < 0.05). The incidence of PHN was significantly lower in the HPO group than in the HP group (P < 0.05). There were no significant differences in adverse events between the groups. CONCLUSIONS: High-voltage PRF is a safe and effective method for treating AZN. The combination of high-voltage PRF and O2-O3 injection is superior to high-voltage PRF alone for treating late-stage AZN. This approach could be recommended as an alternative treatment for patients with refractory AZN and could significantly reduce the risk of PHN.


Asunto(s)
Herpes Zóster , Neuralgia Posherpética , Neuralgia , Ozono , Tratamiento de Radiofrecuencia Pulsada , Tramadol , Humanos , Tratamiento de Radiofrecuencia Pulsada/métodos , Estudios Retrospectivos , Ozono/uso terapéutico , Oxígeno , Gabapentina , Neuralgia Posherpética/tratamiento farmacológico , Herpes Zóster/complicaciones , Neuralgia/terapia
5.
Acta Pharmaceutica Sinica ; (12): 2453-2460, 2022.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-937058

RESUMEN

Wuzhi tablet (WZ) is a prescribed herbal medicine extracted from Schisandra sphenanthera, which is widely used to protect the liver injury and drug-induced hepatotoxicity in clinical practices. Previous studies showed that WZ significantly increased the blood concentrations of tacrolimus, cyclosporine A, paclitaxel by inhibiting the cytochrome P450 3A (CYP3A)-mediated metabolism. CYP3A4 and CYP3A5 are the most important isoenzymes among the CYP3A subfamily. However, there are some differences in the catalytic and inhibitory activities between CYP3A4 and CYP3A5, which may lead to different risk of drug-drug and herb-drug interactions, and the risks may be further amplified in vivo. Currently, few reports have compared the herbal medicine inhibitory effects between CYP3A4 and CYP3A5 mediated metabolic reactions. Therefore, detailing the inhibitory effect of WZ on CYP3A4 and CYP3A5 will help understand and predict the potential herb-drug interaction. The results showed that WZ inhibited CYP3A4 and CYP3A5 in a NADPH-, time- and concentration- dependent manner. WZ showed more potent inhibition on CYP3A5 than CYP3A4. Cautions warranted when combining WZ with other therapeutic drugs to avoid the potential herb-drug interaction.

6.
Plant Sci ; 312: 111043, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34620441

RESUMEN

ζ-Carotene desaturase (ZDS) is one of the key enzymes regulating carotenoids biosynthesis and accumulation. Celery transgenic efficiency is low and it is difficult to obtain transgenic plants. The study on ZDS was limited in celery. Here, the AgZDS gene was cloned from celery and overexpressed in Arabidopsis thaliana and celery to verify its function. The AgZDS has typical characteristic of ZDS protein and is highly conserved in higher plants. Phylogenetic analysis showed that AgZDS has the closest evolutionary relationship with ZDSs from Solanum lycopersicum, Capsicum annuum and Tagetes erecta. Overexpression of AgZDS gene in A. thaliana and celery resulted in increased accumulations of lutein and ß-carotene and up-regulated the expression levels of the genes involved in carotenoids biosynthesis. The contents of lutein and ß-carotene in two lines, AtL1 and AgL5, were the highest in transgenic A. thaliana and celery, respectively. The relative expression levels of 5 genes (AtPDS, AtZISO, AtZEP, AtNCED3, and AtCCD4) were up-regulated compared to the wild type plants. The relative expression levels of most genes in carotenoids biosynthesis pathway, such as AgPDS, AgCRTISO1, and AgZISO, were up-regulated in transgenic celery plants. The antioxidant capacity of A. thaliana and photosynthetic capacity of celery were also enhanced. This research is the first report on the function of structure gene related to carotenoid biosynthesis in transgenic celery plants. The findings in this study demonstrated the roles of AgZDS in regulating carotenoids metabolism of celery, which laid a potential foundation for quality improvement of celery.


Asunto(s)
Apium/genética , Apium/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Luteína/biosíntesis , Oxidorreductasas/metabolismo , beta Caroteno/biosíntesis , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Luteína/genética , Oxidorreductasas/genética , Plantas Modificadas Genéticamente , Verduras/genética , beta Caroteno/genética
7.
Biomed Res Int ; 2021: 2593748, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34447850

RESUMEN

Artificial intelligence technologies such as machine learning have been applied to protein engineering, with unique advantages in protein structure, function prediction, catalytic activity, and other issues in recent years. Screening better mutants is still a bottleneck in protein engineering. In this paper, a new sequence-activity relationship method was analyzed for its application in improving the thermal stability of Aspergillus terreus (R)-ω-selective amine transaminase. The experimental data from 6 single-point mutated enzymes were used as a learning dataset to build models and predict the thermostability of 26 mutants. Based on digital signal processing (DSP), this method digitized the amino acid sequence of proteins by fast Fourier transform (FFT) and then established the best model applying partial least squares regression (PLSR) to screen out all possible mutants, especially those with high performance. In protein engineering, the innovative sequence activity relationship (ISAR) method can make a reasonable prediction using limited experimental data and significantly reduce the experimental cost. The half-life (T 1/2) of (R)-ω-transaminase was fitted with the amino acid sequence by the ISAR algorithm, resulting in an R 2 of 0.8929 and a cvRMSE of 4.89. At the same time, the mutants with higher T 1/2 than the existing ones were predicted, laying the groundwork for better (R)-ω-transaminase in the later stage. The ISAR algorithm is expected to provide a new technique for protein evolution and screening.


Asunto(s)
Aminas/química , Aspergillus/enzimología , Aprendizaje Automático , Transaminasas/química , Aminas/metabolismo , Aspergillus/química , Calor , Modelos Moleculares , Ingeniería de Proteínas/métodos , Estabilidad Proteica , Elementos Estructurales de las Proteínas , Especificidad por Sustrato , Transaminasas/metabolismo
8.
Mol Biotechnol ; 63(7): 638-649, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33973142

RESUMEN

Carotenoids are the general term of natural pigments. The formation of plant color is probably related to the components of carotenoids. As the yellow variety of celery, it is rich in the composition and content of carotenoids. However, the transcript profiling and roles of the genes related to carotenoids biosynthesis in yellow celery remain unclear. In this study, three yellow celery cultivars at different growth stages were used to analyze the content and composition of carotenoids and transcriptional changes of carotenoid biosynthesis-related genes. The lutein and ß-carotene were detected in yellow celery cultivar, while α-carotene and lycopene were not detected. The contents of lutein and ß-carotene were higher in leaf blades than in petioles. During the growth and development, the contents of lutein and ß-carotene gradually decreased in celery. Compared with the other two cultivars, the contents of lutein and ß-carotene were the highest in 'Huangtaiji' of 65 days after sowing (DAS) and 85 DAS and 'Liuhehuangxinqin' of 105 DAS, respectively. The expression levels of AgLCYB and AgPSY2 genes were significantly correlated with lutein and ß-carotene contents. This work provided a reference for the further study on carotenoid metabolisms in yellow celery and also made sense on the way of cultivating yellow celery with high carotenoids content.


Asunto(s)
Apium/crecimiento & desarrollo , Carotenoides/metabolismo , Perfilación de la Expresión Génica/métodos , Proteínas de Plantas/genética , Apium/química , Apium/genética , Regulación de la Expresión Génica de las Plantas , Luteína/metabolismo , Fenotipo , Hojas de la Planta/química , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , beta Caroteno/metabolismo
9.
Dermatol Ther ; 34(2): e14720, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33369827

RESUMEN

Sporotrichosis is a fungal disease of the human and other mammals, caused by a complex of Sporothrix schenckii. The disease follows the traumatic inoculation to lead to fixed lesions, regional lymphangitic lesions, or even disseminated lesions including internal involvement, which depends on host immunological status and strain virulence. In this work, we observed the role of CD4+ T cells apoptosis and conversion of Th1/Th2-type cytokines in the cellular immunity regulation on mice model sporotrichosis. The experiments showed that there was more CD4+ T cells apoptosis, by endogenous apoptosis signaling pathway (P < .05), and more conversions of Th1/Th2-type cytokines in more severe and longer duration groups (P < .05). Meanwhile, the trends of the conversions of Th1/Th2-type cytokines were almost consistent with the CD4 + T cell's apoptosis in the corresponding groups. These findings suggest that CD4+ T cells apoptosis and conversion of Th1/Th2-type cytokines are contributing to promoting the progress of sporotrichosis.


Asunto(s)
Apoptosis , Citocinas/inmunología , Esporotricosis/inmunología , Células TH1/inmunología , Animales , Ratones , Sporothrix
10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-880035

RESUMEN

METHODS@#From January 2005 to December 2013, 83 patients with refractory/recurrent CD20@*RESULTS@#All the patient achieved complete response. The median follow.up time was 39 months. Both the two groups collected peripheral blood stem cells successfully, and had no difference in hematopoietic reconstitution time. Three patients in treatment group and six patients in control group relapsed and the three year overall survival and EFS in treatment group was significantly higher than that in control group, that is(93.0% vs 73.1%, P=0.037) and (89.5% vs 65.4%, P=0.034), respectively. Subgroup analysis showed that: compared with the treatment group in which using R in the whole courses(before and after transplantation, and collection of stem cells) was superior to the control group in both OS and EFS, with the OS 97% vs 87.5% (P>0.05) and EFS 97% vs 76.2% (P=0.05) respectively. While stratified by the different courses of rituximab, the OS was 88.9% (1-2 courses, 9 cases), 93.1% (3-4 courses, 29 cases), 94.7%(more than 5 courses,19 cases), and EFS was 77.8%, 89.7% and 94.7%, respectively.@*CONCLUSION@#For the patients with refractory/recurrent CD20


Asunto(s)
Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Supervivencia sin Enfermedad , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Linfoma no Hodgkin/tratamiento farmacológico , Rituximab/uso terapéutico , Trasplante Autólogo , Resultado del Tratamiento
11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-879034

RESUMEN

Kudzu plants in the subfamily sphenoideae of Leguminosae are commonly used herbs in China, Japan, Korea, India and Thailand, with a long history of medicinal use. They are recorded in Chinese Pharmacopoeia, Japanese Pharmacopeia, Korea Pharmacopeia, Ayurveda Pharmacopoeia of India and Flora of Thailand. There are 15-20 species of Pueraria in the world, including 7 species and 2 varieties in China. At present, there are 6 species with medicinal value, such as Pueraria lobata and P. thomsonii. The main chemical components of the genus are isoflavones, flavonoids, terpenes, steroids, coumarins, puerarin glycosides and benzopyrans. A total of 240 compounds have been isolated and identified from this genus, and their pharmacological effects mainly include improvement of the cardiovascular system, antioxidant, hypoglycemic, antipyretic, anti-inflammatory, anti-alcoholic and estrogen-like effects. In this study, chemical constituents and pharmacological activities of Pueraria at home and abroad were systematically summarized, in order to provide references for the material basis, quality control and further development of Pueraria genus.


Asunto(s)
China , Isoflavonas/farmacología , Japón , Raíces de Plantas , Pueraria , República de Corea , Tailandia
12.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-906474

RESUMEN

Oral nanoparticles (NPs) has gradually become a approach to improve oral bioavailability of biopharmaceutics classification system (BCS) Ⅱ, Ⅲ, Ⅳ drugs, and the transmembrane transport mechanism in the gastrointestinal tract largely depends on physicochemical characteristics of NPs. It would be beneficial to design the NPs with high transport efficiency and effectively improve the oral bioavailability of drugs by adopting a reasonable research model to analyze the transmembrane mechanism of the oral NPs and exactly reveal the relationship between the physicochemical properties and the transport mechanism of NPs. This review focused on summarizing the transmembrane approaches of oral NPs, comparing the advantages and disadvantages of the common cell models, concluding the potential interaction between the physicochemical properties and transmembrane process of NPs, and proposing the research strategy of transport mechanism based on in situ intestinal perfusion, with the purpose of discovering a suitable research model for studying the transport mechanism of different NPs, providing a basis for regulating the transport performance of the NPs to improve the oral bioavailability, and expanding the application of oral NPs in the development of new drugs.

13.
Genomics ; 112(6): 5254-5264, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32976976

RESUMEN

The NAC transcription factor participates in various biotic and abiotic stress responses and plays a critical role in plant development. Lignin is a water-insoluble dietary fiber, but it is second only to cellulose in abundance. Celery is the main source of dietary fiber, but its quality and production are limited by various abiotic stresses. Here, AgNAC1 containing the NAM domain was identified from celery. AgNAC1 was found to be a nuclear protein. Transgenic Arabidopsis thaliana plants hosting AgNAC1 have longer root lengths and stomatal axis lengths than the wide type (WT). The evidence from lignin determination and expression levels of lignin-related genes indicated that AgNAC1 plays a vital role in lignin biosynthesis. Furthermore, the results of the physiological characterization and the drought and salt treatments indicate that AgNAC1-overexpressing plants are significantly resistive to salt stress. Under drought and salt treatments, the AgNAC1 transgenic Arabidopsis thaliana plants presented increased superoxide dismutase (SOD) and peroxidase (POD) activities and decreased malondialdehyde (MDA) content and size of stomatal apertures relatively to the WT plants. The AgNAC1 served as a positive regulator in inducing the expression of stress-responsive genes. Overall, the overexpressing AgNAC1 enhanced the plants' resistance to salt stress and played a regulatory role in lignin accumulation.


Asunto(s)
Apium , Lignina/biosíntesis , Proteínas de Plantas/fisiología , Tolerancia a la Sal/genética , Factores de Transcripción/fisiología , Apium/genética , Arabidopsis/anatomía & histología , Arabidopsis/genética , Arabidopsis/metabolismo , Sequías , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/anatomía & histología , Plantas Modificadas Genéticamente/metabolismo , Homología de Secuencia , Factores de Transcripción/química , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
14.
Sheng Li Xue Bao ; 72(4): 449-454, 2020 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-32820307

RESUMEN

The paper was aimed to explore the role of serum exosomes induced by hepatic ischemia/reperfusion (I/R) injury in the damage of hippocampus and cerebral cortex of rats. The male Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham operation group (S), hepatic I/R injury group (I/R), serum exosomes from S group treatment group (ES) and serum exosomes from I/R group treatment group (EI). In ES group and EI group, 100 µL serum exosomes from S group and I/R group were injected into the normal rats through tail vein respectively. Another three normal rats were injected intravenously with serum exosomes labeled with PKH26 red fluorescence, and then the expression of fluorescence in the brain tissues was observed by immunofluorescence microscope. The morphology and size of exosomes were observed by transmission electron microscope, the expression of exosomes markers CD63 and CD9 was detected by Western blot, and the damage of liver and brain, levels of apoptosis and oxidative stress response in hippocampus and cerebral cortex were observed by serological and histological indexes. The results showed that the exosomes were a group of round or ovoid membranous vesicles, sized in 30-100 nm. Compared with that in S group, the content of serum exosomes in I/R group was increased (P < 0.05). Moreover, serum exosomes could go through the blood-brain barrier and enter the brain tissue freely through blood circulation. The index of liver function in I/R group was significantly higher than that in S group (P < 0.05). There was no significance in the degree of brain damage, apoptosis and oxidative stress in hippocampus and cerebral cortex between S group and ES group. Compared with those in S group and ES group, the serum levels of brain injury markers, apoptosis index (AI) and oxidative stress in hippocampus and cerebral cortex increased in I/R group and EI group (P < 0.05). Whereas, compared with those in I/R group, the above indicators in EI group decreased (P < 0.05). Therefore, hepatic I/R injury can lead to the damage of hippocampus and cerebral cortex, and the increased serum exosomes induced by hepatic I/R plays an important role.


Asunto(s)
Isquemia Encefálica , Exosomas , Daño por Reperfusión , Animales , Hipocampo , Hígado , Masculino , Ratas , Ratas Sprague-Dawley
15.
Chem Biol Interact ; 323: 109061, 2020 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-32194039

RESUMEN

Oncogenic alterations in the BRAF gene are identified in an estimate of 50% of melanomas and cause melanoma development. BRAF kinase inhibitors (BRAFi), including vemurafenib and dabrafenib, were discovered and used in the clinical treatment of BRAF-mutant metastatic melanoma. Though, BRAFi's therapeutic advantages are short term and short-lived associated with drug resistance. Although a few pathways of developed BRAFi resistance have also been established, in approximately 40% of melanomas, the cause for inherited resistance remains unclear. Recognizing a new process of developed BRAFi resistance might provide new possibilities to successfully treat BRAF mutant melanoma. In this study, we are exploring the compensatory alternative pathway followed by BRAFi/MEKi treated resistant cell for maintaining the long-term integrity and survival.


Asunto(s)
Citoprotección , Resistencia a Antineoplásicos , Melanoma/patología , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Transducción de Señal , Neoplasias Cutáneas/patología , Humanos , Proteínas Proto-Oncogénicas B-raf/metabolismo , Melanoma Cutáneo Maligno
17.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-818366

RESUMEN

Objective Trihostatin A (TSA) is a histone deacetylase inhibitor of oxime salts, which has certain anti-tumor activity. This article mainly investigates the molecular mechanism of TSA inhibiting cell proliferation through p-AKT/p-mTOR pathway in gastric cancer cells. Methods Gastric cancer cell line-SGC-7901 were treated with TSA of different concentrations, and the inhibition rate of TSA on the cells was detected by MTT assay. The cells were divided into control group (without any treatment), TSA-treated group (200ng/ml TSA), p-AKT covering group (200 ng/mL TSA+8 μg/mL SC79) and autophagy inhibition group (5 mmol/mL 3-methyladenine+200 ng/mL TSA). The protein expression distribution of Lc3 in control and TSA group were detected by cell immunofluorescence staining. The relative expression levels of p-AKT, p-mTOR and autophagy related proteins Lc3 and P62 in control group, TSA group and p-AKT covering group were detected by Western blot. The proliferation of cells in control group, TSA group, p-AKT covering group and autophagy inhibition group were measured by EdU and cell count assay. Results After 24h of treatment, Lc3 in TSA group formed a large number of granular aggregates in the cytoplasm, and the fluorescence distribution changed from the initial diffuse to dense. The TSA group showed a significant reduction in green fluorescence compared with the control group in the EdU experiment. The expression levels of p-AKT in the control group, TSA group and the autophagy inhibition group were 1.78±0.19, 0.92±0.03 and 1.71±0.19, respectively, and Lc3 were 0.21±0.01, 0.79±0.06 and 0.55±0.10, respectively. Compared with the control group, the relative expression level of p-AKT in the TSA group all decreased, while the expression level of Lc3 increased (P <0.05). p-mTOR in the three groups was 0.80±0.16, 0.45±0.04 and 0.98±0.16, respectively. Compared with the control group, the relative expression level of p-mTOR in the TSA group all decreased (P <0.05). P62 in the three groups was 1.17±0.15, 0.48±0.08 and 0.77±0.10, respectively. Compared with the control group, the relative expression level of P62 in the TSA group all decreased (P<0.05). Compared with the TSA group, p-AKT, p-mTOR and P62 expression in the p-AKT covering group increased (P<0.05), while Lc3 expression decreased (P<0.05). Compared with the control group, the inhibition effect of cell growth curve was the most obvious in the TSA group, while the cell growth curve of p-AKT covering group and autophagy inhibition group showed a partial recovery compared with the TSA group. Conclusion TSA can promote autophagy by inhibiting p-AKt/p-mTOR pathway, thus inhibiting the proliferation of gastric cancer cells.

18.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-846443

RESUMEN

Objective: To investigate the mechanism of sovereign medicines in Sanren Decoction on coronavirus disease 2019 (COVID-19) through network pharmacology and molecular docking methods. Methods: The main active ingredients of sovereign medicines in Sanren Decoction (Armeniacae Semen Amarum, Amomun kravanh Pierre ex Gagnep, and Coicis Semen) were obtained and screened from by TCMSP and TCMID V2.0, combined with related research. Using UniPort database to query the target proteins corresponding to the active ingredients, then a component-target network was constructed by Cytoscape 3.7.2. PPI network was constructed through the STRING website, and cytoHubba was used to analysis the key subnetworks. CTD database was used to analyze GO and KEGG enrichment of the active ingredient target proteins of Sanren Decoction. Using the active ingredients of sovereign medicines in Sanren Decoction and related chemical drugs such as lopinavir as ligands, molecular docking with the SARS-CoV-2 3CL hydrolase was performed through the CB-Dock website. Results: Sovereign medicines in Sanren Decoction had 39 active ingredients, corresponding to 168 target proteins. The GO enrichment analysis obtained 25 biological processes (BP) items, 14 related items of cell composition (CC), and two molecular function (MF) item, respectively. KEGG enrichment screened 36 signaling pathways such as innate immune system, cytokine signaling in immune system, signaling by interleukins. The molecular docking results suggested that the active ingredients of mairin, ziziphin_qt, and oleanolic acid of sovereign medicines in Sanren Decoction had good binding energy with SARS-CoV-2 3CL hydrolase, and the Vina score of them were similar to those of lopinavir (the 3CLpro inhibitor) and remdesivir (RNA-dependent RNA polymerase inhibitor). Conclusion: Sovereign medicines in Sanren Decoction may participate in inflammation-related signaling pathways by regulating inflammatory factors, regulating multiple physiological processes of the disease with multi-components, multi-targets, and multi-pathways. It plays a certain intervention role in the treatment of COVID-19 and its active ingredients have potential resistance to SARS-CoV-2.

19.
Hepatobiliary Pancreat Dis Int ; 17(6): 496-501, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30205926

RESUMEN

BACKGROUND: Body temperature is poorly regulated in patients with end-stage liver disease. Due to the prolonged surgery time and anhepatic time as well as the complex surgical procedures performed in liver transplantation, the body temperature fluctuates greatly. This study investigated the effect of intraoperative body temperature fluctuations on the prognosis of liver recipients. METHODS: The body temperatures of liver recipients recorded from the induction of anesthesia (T0) until the end of surgery (T14) were retrieved. The patients were divided into two groups: the hypothermia group (< 35 °C and ≥ 5 min) and the normothermia group (≥ 35 °C or < 35 °C but < 5 min). Intraoperative and postoperative variables were compared between the two groups, and the correlations between the duration of hypothermia and the medical variables were analyzed. RESULTS: Of the 107 patients, 67 patients were in the normothermia group, and 40 in the hypothermia group. The lowest body temperature was at 5 min after reperfusion for the whole cohort. Compared with the normothermia group, patients in the hypothermia group were more prone to bleeding, had a longer intubation time and increased rates of bacterial infection and acute pulmonary edema after liver transplantation (P < 0.05). Hypothermia time was positively correlated with bleeding volume, intubation time, units of blood transfusions and intensive care stay, but negatively correlated with urine output. CONCLUSIONS: The intraoperative body temperature exhibited a graphical "V" trend, and the lowest temperature was at 5 min after reperfusion. The longer the duration of hypothermia, the more unfavourable the prognosis.


Asunto(s)
Temperatura Corporal , Trasplante de Hígado , Adulto , Femenino , Humanos , Hipotermia/complicaciones , Periodo Intraoperatorio , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Tiempo
20.
Acta Pharmaceutica Sinica ; (12): 765-770, 2018.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-779934

RESUMEN

The study was designed to investigate the effect of IMPDH1 gene polymorphism on the pharmacodynamics of mycophenolic acid in the renal transplant patients. 315 patients with renal transplantation were treated with triple immunotherapy (mycophenolic acid + tacrolimus + prednisone). The Agena MassARRAY assay was used to detect the IMPDH1 genotypes in patients above. The plasma drug concentration of mycophenolic acid (MPA) and its main metabolite mycophenolic acid glucuronide (MPAG) was detected by high performance liquid chromatography (HPLC). The correlation between IMPDH1 gene polymorphism (rs10954183, rs12536006, rs13242340, rs2278293, rs2288549) and rejection and postoperative infection in renal transplant recipients were analyzed by SPSS 21 software. The result showed that IMPDH1 rs2288549 GG is a risk factor for acute rejection after renal transplantation (PIMPDH1 rs2278293 CT is a risk factor for infection after renal transplantation (PIMPDH1 rs2288549 is an important factor of acute rejection after renal transplantation, IMPDH1 rs2278293 is an important factor affecting the emergence of infection after renal transplantation. The SNPs may help to optimize clinical medication to reduce the incidence of adverse reaction.

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