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1.
Medicine (Baltimore) ; 103(14): e37633, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38579084

RESUMEN

BACKGROUND: The quality control circle (QCC) model has achieved good results in clinical applications in many hospitals in China and has gained popularity. This study aims to explore the application of QCC activities on early ambulation after cesarean section. METHODS: A QCC management group was established following standardized methods and techniques. The theme of the group was identified as "to enhance the implementation rate of the patient early ambulation after the cesarean section" through a matrix graph. The early ambulation rates after surgery of patients who received cesarean section were compared before and after QCC managements. RESULTS: Our data suggested that the early ambulation rates after cesarean section increased from 37.5% to 81.25% after applying QCC management. The biggest factor influencing the ambulation activities 24 ±â€…4 hours after the surgery was patients and family members do not cooperate. In addition, outstanding improvements in terms of nurses' sense of responsibility and self-confidence, communication and teamwork capacity in the problem-solving process were observed after the establishment of QCC. CONCLUSION: The application of QCC management had not only increase the early ambulation rates after cesarean section but also improved the quality of nursery care in general.


Asunto(s)
Cesárea , Ambulación Precoz , Humanos , Embarazo , Femenino , Hospitales , Control de Calidad , China
2.
J Pept Sci ; : e3572, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38396336

RESUMEN

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2 O2 -induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 µg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.

3.
Heliyon ; 9(8): e18708, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37554782

RESUMEN

Background: Ovarian serous cystadenocarcinoma (OSC) is the most prevalent histological subtype of ovarian cancer (OV) and presents a serious threat to women's health. Anoikis is an essential component of metastasis, and tumor cells can get beyond it to become viable. The impact of anoikis on OSC, however, has only been the topic of a few studies. Methods: The mRNA sequencing and clinical information of OSC came from The Cancer Genome Atlas Target Genotype-Tissue Expression (TCGA TARGET GTEx) dataset. Anoikis-related genes (ARGs) were collected by Harmonizome and GeneCards websites. Centered on these ARGs, we used unsupervised consensus clustering to explore potential tumor typing and filtered hub ARGs to create a model of predictive signature for OSC patients. Furthermore, we presented clinical specialists with a novel nomogram based on ARGs, revealing the underlying clinical relevance of this signature. Finally, we explored the immune microenvironment among various risk groups. Results: We identified 24 ARGs associated with the prognosis of OSC and classified OSC patients into three subtypes, and the subtype with the best prognosis was more enriched in immune-related pathways. Seven ARGs (ARHGEF7, NOTCH4, CASP2, SKP2, PAK4, LCK, CCDC80) were chosen to establish a risk model and a nomogram that can provide practical clinical decision support. Risk scores were found to be an independent and significant prognostic factor in OSC patients. The CIBERSORTx result revealed an inflammatory microenvironment is different for risk groups, and the proportion of immune infiltrates of Macrophages M1 is negatively correlated with risk score (rs = -0.21, P < 0.05). Ultimately, quantitative reverse transcription polymerase chain reaction (RT-PCR) was utilized to validate the expression of the seven pivotal ARGs. Conclusion: In this study, based on seven ARGs, a risk model and nomogram established can be used for risk stratification and prediction of survival outcomes in patients with OSC, providing a reliable reference for individualized therapy of OSC patients.

4.
Int J Gen Med ; 16: 2897-2921, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37457751

RESUMEN

Background: Endometriosis, a common gynecological condition, can cause symptoms such as dysmenorrhea, infertility, and abnormal bleeding, which can negatively affect a woman's quality of life. In the current study, the pathophysiological mechanisms of endometriosis are unknown, but this study suggests that endometriosis is associated with dysregulation of the autoimmune system. This study identify hub genes involved in the prevalence, identification and diagnostic value of endometriosis and autoimmune diseases, and explore the central genes and immune infiltrates, the diagnosis of endometriosis provides a new sight of thinking about diagnosis and treatment. Methods and Results: The relevant datasets for endometriosis GSE141549, GSE7305 and autoimmune disease-related genes (AIDGs) were downloaded from online database. Using the "limma" package and WGCNA to screen out the autoimmune disease related genes and endometriosis related genes, the autoimmune disease gene-related differential genes (AID-DEGs) progressive GO, KEGG enrichment analysis, and then using the protein interaction network and Cytoscape software to select hub genes (CXCL12, PECAM1, NGF, CTGF, WNT5A), using the "pROC" package to analyze the hub genes for the diagnostic value of endometriosis. The difference in the importance of hub genes for the diagnosis of endometriosis was analyzed by machine learning random forest, and the combined diagnostic value of hub genes was analyzed by using the Support Vector Machine (SVM) algorithm. The eutopic (EU) and ectopic endometrium (EC) immune microenvironment of endometriosis was evaluated using CIBERSORT, the correlation of hub genes to the immune microenvironment was analyzed. Conclusion: The hub genes associated with AIDGs are differentially expressed in EC and EU of endometriosis and possess important value for the diagnosis of endometriosis. The hub genes have a very important impact on the immune microenvironment of endometriosis, which is important for exploring the connection between endometriosis and autoimmune diseases and provides a new insight for the subsequent study of immunotherapy and diagnosis of endometriosis.

5.
Medicina (Kaunas) ; 59(2)2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36837559

RESUMEN

Background and Objectives: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are malignant disorders with adverse prognoses for advanced patients. Anoikis, which is involved in tumor metastasis, facilitates the survival and separation of tumor cells from their initial site. Unfortunately, it is rarely studied, and in the literature, studies have only addressed the prognosis character of anoikis for patients with CESC. Materials and Methods: We utilized anoikis-related genes (ANRGs) to construct a prognostic signature in CESC patients that were selected from the Genecards and Harmonizome portals. Furthermore, we revealed the underlying clinical value of this signature for clinical maneuvers by providing clinical specialists with an innovative nomogram on the basis of ANRGs. Finally, we investigated the immune microenvironment and drug sensitivity in different risk groups. Results: We screened six genes from fifty-eight anoikis-related differentially expressed genes in the TCGA-CESC cohort, and we constructed a prognostic signature. Then, we built a nomogram combined with CESC clinicopathological traits and risk scores, which demonstrated that this model may improve the prognosis of CESC patients in clinical therapy. Next, the prognostic risk scores were confirmed to be an independent prognostic indicator. Additionally, we programmed a series of analyses, which included immune infiltration analysis, therapy-related analysis, and GSVA enrichment analysis, to identify the functions and mechanisms of the prognostic models during the progression of cancer in CESC patients. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the six ANRGs. Conclusions: The present discovery verified that the predictive 6-anoikis-related gene (6-ANRG) signature and nomogram serve as imperative factors that might notably impact a CESC patient's prognosis, and they may be able to provide new clinical evidence to assume the role of underlying biological biomarkers and thus become indispensable indicators for prospective diagnoses and advancing therapy.


Asunto(s)
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias de Tejido Conjuntivo , Neoplasias del Cuello Uterino , Femenino , Humanos , Anoicis , Pronóstico , Estudios Prospectivos , Microambiente Tumoral
6.
Diabetes Metab Syndr Obes ; 15: 973-981, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35386588

RESUMEN

Objective: The present study aims to evaluate the relationship of thyroid function during the first trimester of pregnancy with lipid levels and pregnancy outcomes. Methods: Women who delivered babies at the Shanghai General Hospital between March 2019 and December 2019 with a known pregnancy outcome and complete data were included in the present study (n = 1779). A retrospective cohort study of all subjects with available first-trimester thyroid function testing and lipid levels data was conducted, and the relationship of thyroid function with lipid levels and pregnancy outcomes was evaluated. The data were analyzed using the SPSS software for statistical correlation. Results: The proportion of caesarean sections was higher in women with hypothyroxinemia (HIA) and hypothyroidism than in women with euthyroidism. Hypothyroidism was shown to be related with polyhydramnios, preterm labor and hypertriglyceridemia. HIA was correlated with increased rates of gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension and hypertriglyceridemia. Compared with the euthyroidism group, the hypothyroidism group had a higher apolipoprotein A1 (Apo A1) level and apolipoprotein B level; the subclinical hypothyroidism group had a higher total cholesterol (TC) level and low-density lipoprotein cholesterol level; the HIA group had higher triglyceride, high-density lipoprotein cholesterol levels and lower TC, Apo A1 levels. TC levels were positively correlated with the thyroid-stimulating hormone level and negatively correlated with free thyroxine (FT4) level, and free triiodothyronine and FT4 levels were positively correlated with GDM occurrence. Conclusion: Thyroid function in early pregnancy is associated with dyslipidemia and pregnancy outcomes; conventional screening of thyroid diseases in early pregnancy may help improve lipid levels and decrease adverse pregnancy outcomes.

7.
Iran J Immunol ; 19(1): 3, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35293344

RESUMEN

BACKGROUND: The methylation of IFN-γ and IL-4 genes is regarded as an epigenetic regulation that maintains the Th1 or Th2 phenotype. OBJECTIVE: To explore the influence of prenatal administration of the staphylococcal enterotoxin B (SEB) in pregnant rats, on the IFN-γ or IL-4 expression in the offspring spleen. METHODS: The SEB or PBS was administered intravenously to pregnant rats on the embryo-day 16. After normal delivery, the spleens from the fifth-day neonates and adult offspring were isolated under anesthesia. Quantitative PCR, western blot, ELISA and MeDIP-qPCR were applied to determine the levels of the splenic IFN-γ or IL-4 mRNAs, their protein levels, and methylation status, respectively. RESULTS: Prenatal administration of the SEB in pregnant rats decreased the levels of the splenic IFN-γ and IL-4 proteins in neonates, but increased their mRNA levels. However, prenatal administration of the SEB significantly augmented both mRNA and protein levels of the IFN-γ and IL-4 in the adult spleen. In addition, the prenatal SEB administration decreased the methylation of the splenic IFN-γ and IL-4 in adult but not neonatal offspring. CONCLUSION: The prenatal administration of SEB in pregnant rats can cause a mixed Th1 and Th2 cytokines response in the offspring spleen, and alter the cytokine expression of the Th1 and Th2 via decreasing the methylation in adult but, not neonatal offspring spleen.


Asunto(s)
Citocinas , Efectos Tardíos de la Exposición Prenatal , Animales , Citocinas/metabolismo , Enterotoxinas , Epigénesis Genética , Femenino , Metilación , Embarazo , Efectos Tardíos de la Exposición Prenatal/genética , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas , Bazo/metabolismo
8.
Biomolecules ; 12(3)2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-35327595

RESUMEN

Podocytopathies are kidney diseases that are driven by podocyte injury with proteinuria and proteinuria-related symptoms as the main clinical presentations. Albeit podocytopathies are the major contributors to end-stage kidney disease, the underlying molecular mechanisms of podocyte injury remain to be elucidated. Mitochondrial oxidative stress is associated with kidney diseases, and increasing evidence suggests that oxidative stress plays a vital role in the pathogenesis of podocytopathies. Accumulating evidence has placed mitochondrial oxidative stress in the focus of cell death research. Excessive generated reactive oxygen species over antioxidant defense under pathological conditions lead to oxidative damage to cellular components and regulate cell death in the podocyte. Conversely, exogenous antioxidants can protect podocyte from cell death. This review provides an overview of the role of mitochondrial oxidative stress in podocytopathies and discusses its role in the cell death of the podocyte, aiming to identify the novel targets to improve the treatment of patients with podocytopathies.


Asunto(s)
Enfermedades Renales , Podocitos , Antioxidantes/metabolismo , Muerte Celular , Femenino , Humanos , Enfermedades Renales/metabolismo , Masculino , Estrés Oxidativo/fisiología , Podocitos/metabolismo , Podocitos/patología , Proteinuria/metabolismo , Especies Reactivas de Oxígeno/metabolismo
9.
Acta Pharmacol Sin ; 43(4): 850-861, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34272505

RESUMEN

Amyloid-ß peptide (Aß) aggregation is the hallmark of Alzheimer's disease (AD). The imbalance between the production and clearance of Aß results in the accumulation and aggregation of Aß in the brain. Thus far, few drugs are available for AD treatment, but exercise has been recognized for its cognition-enhancing properties in AD patients. The underlying mechanisms remain unclear. Our recent study showed that long-term running exercise could activate the lysosomal function in the brains of mice. In this study, we investigated whether exercise could reduce Aß accumulation by activating lysosomal function in APP/PSEN1 transgenic mice. Started at the age of 5 months, the mice were trained with a running wheel at the speed of 18 r/min, 40 min/d, 6 d/week for 5 months, and were killed at the end of the 10th month, then brain tissue was collected for biochemical analyses. The cognitive ability was assessed in the 9th month. We showed that long-term exercise significantly mitigated cognitive dysfunction in AD mice, accompanied by the enhanced lysosomal function and the clearance of Aß in the brain. Exercise significantly promoted the nuclear translocation of transcription factor EB (TFEB), and increased the interaction between nuclear TFEB with AMPK-mediated acetyl-CoA synthetase 2, thus enhancing transcription of the genes associated with the biogenesis of lysosomes. Exercise also raised the levels of mature cathepsin D and cathepsin L, suggesting that more Aß peptides could be degraded in the activated lysosomes. This study demonstrates that exercise may improve the cognitive dysfunction of AD by enhancing lysosomal function.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Encéfalo/metabolismo , Disfunción Cognitiva/terapia , Modelos Animales de Enfermedad , Humanos , Lisosomas/metabolismo , Ratones , Ratones Transgénicos , Presenilina-1/genética
10.
Toxicol Appl Pharmacol ; 434: 115814, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34843800

RESUMEN

Di(2-ethylhexyl) phthalate (DEHP) belongs to environmental endocrine disrupting chemicals (EEDCs) and can be rapidly hydrolyzed into the ultimate toxicant mono-2-ethylhexyl phthalate (MEHP). In this study, we used 5-aminofluorescein modified MEHP (MEHP-AF) as a fluorescence tracer to explore the toxicokinetics, including toxicokinetic parameters, absorption and transport across the intestinal mucosal barrier, distribution and pathological changes of organs. While the dose was as lower than 10 mg/kg by intragastric administration, the toxicokinetic parameters obtained by fluorescence microplate method were similar to those with the literatures by chromatography. MEHP-AF can be rapidly absorbed through the intestinal mucosal barrier in rats. In situ organ distribution in mice showed that MEHP-AF was mainly concentrated in the liver, kidney and testis. Our results suggested that the fluorescence tracing technique had the advantages with easy processing, less time-consuming, higher sensitivity for the quantitative determination, In addition, this technology also avoids the interference of exogenous or endogenous DEHP and MEHP in the experimental system. It also can be utilized to the visualization detection of MEHP in situ localization in the absorption organ and the toxic target organ. The results show that this may be a more feasible MEHP toxicological research method.


Asunto(s)
Dietilhexil Ftalato/análogos & derivados , Fluoresceínas/química , Animales , Área Bajo la Curva , Células CACO-2 , Neoplasias Colorrectales , Dietilhexil Ftalato/química , Dietilhexil Ftalato/farmacocinética , Dietilhexil Ftalato/toxicidad , Semivida , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Imagen Óptica , Ratas , Ratas Sprague-Dawley
11.
Int J Gen Med ; 14: 7051-7058, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34707396

RESUMEN

OBJECTIVE: To investigate the value of dual energy CT enterography (DECTE) in evaluating the activity of Crohn's disease (CD). METHODS: The endoscopy and imaging data of 29 patients with CD confirmed by clinic and pathology were analyzed retrospectively. The clinical CD activity index (CDAI) was used as the disease activity grouping standard, 29 patients with CD were grouped into activity groups, 18 patients in the active group (CDAI ≥ 150) with 36 intestinal segments, and 11 patients in the remission group (CDAI < 150) with 20 intestinal segments.The virtual single energy CT value, slope of energy spectrum curve and iodine content were analyzed to evaluate the evaluation of intestinal CD activity by DECTE. RESULTS: There were statistically significant differences in virtual single energy CT value (except 90 keV and 100 keV virtual single energy CT value), curve slope and iodine content between remission group and active group (P < 0.05), and has more diagnostic value for active phase (AUC > 0.5). ① Virtual single energy CT value: the AUC of 60 keV in arterial phase was the highest (0.924). The specificity of diagnosing CD in active stage was high (95%). ② Curve slope: the AUC of portal vein phase was the largest (0.731). The specificity of diagnosing CD in active stage was higher (85%). ③ Iodine content: the AUC of arterial phase was the highest (0.885). The specificity of diagnosing CD lesions in the active stage was 100%. CONCLUSION: The virtual single energy CT value, energy spectrum curve slope and iodine content can provide reference for clinical accurate diagnosis of CD activity.

12.
Curr Med Sci ; 41(4): 635-648, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34403086

RESUMEN

OBJECTIVE: To examine the effect of multisensory exercise on balance disorders. METHODS: PubMed, Scopus and Web of Science were searched to identify eligible studies published before January 1, 2020. Eligible studies included randomized control trials (RCTs), non-randomized studies, case-control studies, and cohort studies. The methodological quality of the included studies was evaluated using JBI Critical Appraisal Checklists for RCTs and for Quasi-Experimental Studies by two researchers independently. A narrative synthesis of intervention characteristics and health-related outcomes was performed. RESULTS: A total of 11 non-randomized studies and 9 RCTs were eligible, including 667 participants. The results supported our assumption that multisensory exercise improved balance in people with balance disorders. All of the 20 studies were believed to be of high or moderate quality. CONCLUSION: Our study confirmed that multisensory exercise was effective in improving balance in people with balance disorders. Multisensory exercises could lower the risk of fall and enhance confidence level to improve the quality of life. Further research is needed to investigate the optimal strategy of multisensory exercises and explore the underlying neural and molecular mechanisms of balance improvement brought by multisensory exercises.


Asunto(s)
Terapia por Ejercicio , Ejercicio Físico/fisiología , Equilibrio Postural/fisiología , Humanos , Calidad de Vida
13.
Adv Exp Med Biol ; 1208: 265-287, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34260029

RESUMEN

Biomarkers (short for biological markers) are biological measures of a biological state. Autophagy biomarkers play an important role as an indicator of autophagy during normal physiological processes, pathogenic processes or pharmacological responses to drugs. In this chapter, some biomarkers of different types of autophagy, including macroautophagy, selective autophagy, chaperone-mediated autophagy, and microautophagy, as well as the lysosomal biomarkers are introduced. The described biomarkers may be used to detect the level of autophagy in cells or tissues in a dynamic, real-time, and quantitative manner. However, each biomarker has its specific significance and limitation. Therefore, the analysis of the autophagy level in cells or tissues through the detection of autophagy biomarkers should be carried out carefully.


Asunto(s)
Autofagia , Lisosomas , Biomarcadores , Microautofagia
14.
Mater Sci Eng C Mater Biol Appl ; 124: 112039, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33947539

RESUMEN

In this study, to improve the intestinal absorption of small molecule chemotherapeutic drug docetaxel (DTX) and macromolecular monoclonal antibody drug bevacizumab (BVZ), we designed and prepared a type of co-delivery nanoparticles for the oral administration of DTX and BVZ. Carboxymethyl chitosan (CMC) and poly(lactic-co-glycolic acid) (PLGA) were used as the carrier of DTX nanoparticles (CPNPDTX), and methoxy polyethylene glycol-poly (ß-amino ester) (mPEG-PAE) was used as the carrier of BVZ nanoparticles (PPNPBVZ). Then, the two nanoparticles were physically mixed in mass ratios to form mixed co-delivery nanoparticles, which was named as CPNPDTX&PPNPBVZ. The nanoparticles were characterized with pH-sensitive drug release property. CPNPDTX&PPNPBVZ could significantly increase the bioavailability of DTX and BVZ according to the more cellular uptake in Caco-2 cells and the higher absorption in the intestinal tissue. Compared with free DTX and BVZ, CPNPDTX&PPNPBVZ showed excellent cytotoxic effects on A549 cells. Our study revealed the potential of co-delivery nanoparticles of binary mixture of chemotherapeutic small molecule and macromolecular antibody drug as an oral administration therapeutic system.


Asunto(s)
Antineoplásicos , Nanopartículas , Administración Oral , Antineoplásicos/farmacología , Bevacizumab/farmacología , Células CACO-2 , Docetaxel/farmacología , Portadores de Fármacos , Humanos , Absorción Intestinal
15.
Immunobiology ; 226(2): 152060, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33529803

RESUMEN

Staphylococcus aureus is an infectious pathogen that is relatively common, but that can cause severe disease in pregnant women and their fetus. We previously demonstrated that exposing pregnant rats to staphylococcal enterotoxin B (SEB) altered splenic CD4/CD8 T cell frequencies in their offspring. Whether prenatal SEB exposure impacts Tregs in these offspring, however, remains to be determined. As such, in this study, we intravenously injected pregnant rats with 15 µg of SEB on gestational day 16. Splenic tissue was then harvested from 1-, 3-, and 5-day-old neonatal rats and analyzed via flow cytometry to assess Treg numbers. In addition, FoxP3 expression levels were assessed via qPCR and western blotting, while FoxP3 methylation status was evaluated via methyl-DNA immunoprecipitation qPCR. Immunosuppression assays were additionally used to gauge Treg suppressive functionality. We found that exposing pregnant rats to SEB resulted in a significant increase in Treg numbers, FoxP3 expression, and Treg suppressive capacity in the spleens of both neonatal and adult offspring. In addition, total T cell, CD4+T cell, and non-Treg CD4+ T cell numbers were elevated in the spleens of offspring following prenatal SEB exposure. We additionally determined that SEB exposure resulted in a significant reduction in FoxP3 DNA methylation. Together, our results indicate that prenatal SEB exposure can markedly enhance offspring splenic Treg numbers and functionality at least in part by decreasing FoxP3 methylation.


Asunto(s)
Enterotoxinas/administración & dosificación , Factores de Transcripción Forkhead/genética , Linfocitos T Reguladores/inmunología , Animales , Metilación de ADN , Femenino , Factores de Transcripción Forkhead/inmunología , Intercambio Materno-Fetal , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas Sprague-Dawley , Bazo/efectos de los fármacos , Bazo/inmunología
16.
Toxicol Appl Pharmacol ; 414: 115411, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33476678

RESUMEN

Di-2-ethylhexyl phosphate (DEHP) and its main toxic metabolite mono-2-ethylhexyl phthalate (MEHP) are the typical endocrine disrupting chemicals (EDCs) and widely affect human health. Our previous research reported that synthetic nonionic dietary emulsifier polysorbate 80 (P80, E433) had the promotional effect on the oral absorption of DEHP in rats. The aim of this study was to explore its mechanism of promoting oral absorption, focusing on the mucus barrier and mucosal barrier of the small intestine. A small molecule fluorescent probe 5-aminofluorescein-MEHP (MEHP-AF) was used as a tracker of MEHP in vivo and in vitro. First of all, we verified that P80 promoted the bioavailability of MEHP-AF in the long-term and low-dose exposure of MEHP-AF with P80 as a result of increasing the intestinal absorption of MEHP-AF. Afterwards, experimental results from Western blot, qPCR, immunohistochemistry, and immunofluorescence showed that P80 decreased the expression of proteins (mucus protein mucin-2, tight junction proteins claudin-1 and occludin) related to mucus barrier and mucosal barrier in the intestine, changed the integrity of intestinal epithelial cell, and increased the permeability of intestinal epithelial mucosa. These results indicated that P80 promoted the oral absorption of MEHP-AF by altering the intestinal mucus barrier and mucosal barrier. These findings are of great importance for assessing the safety risks of some food emulsifiers and clarifying the absorption mechanism of chemical pollutants in food, especially for EDCs.


Asunto(s)
Dietilhexil Ftalato/análogos & derivados , Emulsionantes/toxicidad , Células Epiteliales/efectos de los fármacos , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Polisorbatos/toxicidad , Animales , Disponibilidad Biológica , Células CACO-2 , Claudina-1/metabolismo , Dietilhexil Ftalato/farmacocinética , Dietilhexil Ftalato/toxicidad , Células Epiteliales/metabolismo , Fluoresceínas/metabolismo , Colorantes Fluorescentes/metabolismo , Células HT29 , Humanos , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Masculino , Ratones Endogámicos ICR , Mucina 2/metabolismo , Ocludina/metabolismo , Permeabilidad , Ratas Sprague-Dawley , Distribución Tisular , Toxicocinética
17.
Acta Pharmacol Sin ; 42(4): 624-632, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32704040

RESUMEN

The mechanism underlying the resistance of cancer cells to chemotherapeutic drug varies with different cancer cells. Recent evidence shows that lysosomal function is associated with drug resistance of cancer cells. Artesunate, a derivative of artemisinin, displays broad antitumor activity and direct cytotoxicity on various tumor cells. Our previous study shows that artesunate increases autophagosome accumulation, while significantly decreases autolysosome number in cancer cells, suggesting that artesunate might impair the lysosomal function. In this study, we investigated the effects of artesunate on lysosomal function and its relationship with chemotherapeutic drug resistance in cancer cells. We found that the lysosomal function was significantly enhanced in two drug-resistant (A549/TAX and A549/DDP) cells. Furthermore, we showed that the enhanced lysosomal function by overexpression of transcription factor EB (TFEB) significantly increased MCF-7 cells resistance to doxorubicin (DOX), whereas the decreased lysosomal function by TFEB-knockdown or lysosome inhibitor chloroquine increased MCF-7 cells sensitivity to DOX. Treatment of A549/TAX cells with artesunate (2.5-50 µM) dose-dependently inhibited lysosomal function and the clearance of dysfunctional mitochondria, and induced cell apoptosis. Moreover, we demonstrated that artesunate exerted more potent inhibition on the resistant (A549/TAX and MCF-7/ADR) cells with higher activity of lysosomal function. Our results suggest that artesunate or other inhibitors of lysosomal function would be potential in the treatment of cancer cells with drug resistance caused by the enhanced lysosomal function.


Asunto(s)
Antineoplásicos/farmacología , Artesunato/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Lisosomas/efectos de los fármacos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Catepsinas/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cloroquina/farmacología , Cromanos/farmacología , Doxorrubicina/farmacología , Sinergismo Farmacológico , Técnicas de Silenciamiento del Gen , Humanos , Paclitaxel/farmacología
18.
Eur J Med Chem ; 209: 112563, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33038797

RESUMEN

Phenylethanoid glycosides (PhGs) are compounds made of phenylethyl alcohol, caffeic acid and glycosyl moieties. The first published references about phenylethanoid glycosides concerned the isolation of echinacoside from Echinaceu ungustifolia (Asteraceae) in 1950 and verbascoside from Verbascum sinuatum (Scrophulariaceae) in 1963. Over the past 60 years, many compounds with these structural characteristics have been isolated from natural sources, and most of these compounds possess significant bioactivities, including antibacterial, antitumor, antiviral, anti-inflammatory, neuro-protective, antioxidant, hepatoprotective, and immunomodulatory activities, among others. In this review, we will summarize the phenylethanoid glycosides described in recent papers and list all the compounds that have been isolated over the past few decades. We will also attempt to present and assess recent studies about the separation, extraction, determination, and pharmacological activity of the excellent natural components, phenylethanoid glycosides.


Asunto(s)
Glicósidos/química , Glicósidos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Asteraceae/química , Descubrimiento de Drogas , Humanos , Alcohol Feniletílico/química , Alcohol Feniletílico/farmacología , Plantas/química , Scrophulariaceae/química
19.
Mater Sci Eng C Mater Biol Appl ; 117: 111370, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32919698

RESUMEN

Although combined chemotherapy had achieved the ideal efficacy in clinical anti-cancer therapeutic, the issues that need to be addressed are non-targeting and toxic-side effects of small molecule chemical drug (SMCD). In this study, we designed and prepared a novel binary blended co-delivered nanoparticles (BBCD NPs) with pH-responsive feature on tumor microenvironment. The BBCD NPs consists of two kind of drug-loaded NPs, in one of which carboxymethyl chitosan (CMC) and Poly (lactic-co-glycolic acid) (PLGA) were chosen as delivery carrier to load anti-cancer drug vincristine (VCR), named CMC-PLGA-VCR NPs (or CPNPVCR); and in the other of which methoxy poly(ethylene glycol)-poly(ß-amino ester) (mPEG-PAE) were chosen as delivery carrier to load anti-fibrotic drug pirfenidone (PFD), named mPEG-PAE-PFD NPs (or PPNPPFD). Then, the two types of NPs (CPNPVCR and PPNPPFD) were physically mixed in mass ratios to form BBCD NPs, which was named CPNPVCR&PPNPPFD. CPNPVCR&PPNPPFD had good encapsulation efficiency and loading capacity, and the particle size distribution was uniform. In cytotoxicity experiments and non-contact co-culture studies in vitro, the model drugs loaded in CPNPVCR&PPNPPFD could respectively target cancer cell and cancer associated fibroblast (CAF) owing to the precise pH-sensitive drug release in the pharmacological targets and show stronger synergism than that of the combined treatment of two free drugs. As a modularity and assemble ability feature in design, BBCD NPs would have the advantages on the terms of concise on preparation process, controllable on quality standard, stable in natural environment storage. The research results can provide scientific evidence for the further development of a novel drug co-delivery system with multi-type cell targets.


Asunto(s)
Nanopartículas , Microambiente Tumoral , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Concentración de Iones de Hidrógeno , Tamaño de la Partícula , Polietilenglicoles , Copolímero de Ácido Poliláctico-Ácido Poliglicólico
20.
Huan Jing Ke Xue ; 41(5): 2390-2397, 2020 May 08.
Artículo en Chino | MEDLINE | ID: mdl-32608858

RESUMEN

This study used a reducing agent to regulate the activity of heavy metals in soil, with the aim of enhancing the washing efficiency of heavy metals in soil by ethylene glycol bis (2-aminoethyl ether) tetraacetic acid (EGTA). The effects of EGTA dosage, reductant type, liquid-solid ratio, and leaching time on washing efficiency were studied. The heavy metal concentrations in the washing solution and the chemical specification under different washing conditions were analyzed. Scanning electron microscopy/energy-dispersive X-ray spectroscopy and Fourier-transform infrared spectroscopy were used to characterize the soil samples under different treatments. The results showed that the washing efficiencies of Cu, Zn, Pb, and Cd were 85.0%, 60.7%, 88.6%, and 66.4%, respectively, when the liquid-solid ratio was 7.5:1, the leaching time was 2 h, and the dosage of EGTA and sodium thiosulfate (Na2S2O3) was 5 g·L-1. Compared with single EGTA treatment, the leaching concentration of the four heavy metals all decreased, with the Pb decreasing most significantly. The soil particles became smaller, the aggregate structure was destroyed, the O and Al content decreased, the Si content increased, and therefore the adsorption capacity of soil mineral components was supposed to decrease. The soil organic matter content decreased significantly, and the -OH vibration was significantly weakened, indicating that the organic functional groups with stronger coordination ability were reduced, and the adsorption of organic components in the soil was reduced. The decrease in content of strongly adsorbed components in soil is an important mechanism for Na2S2O3 to enhance heavy metal elution by EGTA.

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