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1.
Chem Sci ; 13(32): 9243-9248, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36093029

RESUMO

Supramolecular sequestration and reversal of neuromuscular block (NMB) have great clinical applications. Water-soluble flexible organic frameworks (FOFs) cross-linked by disulfide bonds are designed and prepared. Different linker lengths are introduced to FOFs to give them varied pore sizes. FOFs are anionic nanoscale polymers and capable of encapsulating cationic neuromuscular blocking agents (NMBAs), including rocuronium (Roc), vecuronium (Vec), pancuronium (Panc) and cisatracurium (Cis). A host-guest study confirms that FOFs bind NMBAs in water. The multivalency interaction between FOFs and NMBAs is able to sequester NMBAs, and prevent them from escaping. These FOFs are non-toxic and biocompatible. Animal studies show that FOFs are effective for the reversal of NMB induced by Roc, Vec and Cis, which shorten the time to a train-of-four ratio of 0.9 by 2.6, 3.8 and 5.7-fold compared to a placebo, respectively.

2.
Platelets ; : 1-8, 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36120827

RESUMO

Bacteremia frequently occurs in patients with acute cholangitis, which could increase the risk of mortality. This single-center retrospective observational study was conducted from July 2013 to July 2020 to evaluate the predictive value of platelet index for bacteremia at admission for acute cholecystitis. A total of 285 patients with acute cholangitis were divided into bacteremia group and non-bacteremia group. The incidence of bacteremia in acute cholangitis was 48.42%. The bacteremia group had more grade III patients, higher 30d mortality rate [17(12.32%) vs 8(5.44%), p = .040] and higher incidence of thrombocytopenia [76(55.07%) vs 35(23.81%), p < .001]. Platelet counts and plateletcrit were significantly lower in the bacteremia group [84.5(60, 180) vs 162(102,225) ×109/L and 0.10(0.07, 0.21)% vs 0.18(0.12, 0.25) %, both p < .001]. ROC analysis indicated a high predictive value of platelet count and plateletcrit for bacteremia in patients with acute cholangitis and the area under the ROC curve (AUC) were 0.649 and 0.655, respectively. These results support the value of platelet count and plateletcrit in early prediction of bacteremia at admission for acute cholangitis.


What is the context? Acute cholangitis is a fatal infectious disease. Bacteremia frequently occur in patients with acute cholangitis, which could increase the risk of mortality.The positive rate of blood cultures in patients with acute cholangitis ranged from 21% to 71%.Platelets play key roles in thromboembolism, inflammation, and immune regulation.To the best of our knowledge, whether platelet index facilitates to the diagnosis of bacteremia in acute cholangitis has not been investigated.What is new?In this study, we designed this 7-year retrospective, observational study to verify that platelet index could contribute to the early diagnosis of bacteremia in acute cholangitis.The results showed that:The patients with bacteremia had a higher incidence of thrombocytopenia.Thrombocytopenia, platelet count, plateletcrit, and procalcitonin were independent risk factors for bacteremia in acute cholangitisPlatelet count and plateletcrit had positive predictive value for bacteremia in acute cholangitis.What is the impact?This study presents clinical characteristics of acute cholangitis complicated by bacteremia, and provides evidence that platelet index can be used to predict bacteremia in acute cholangitis.

4.
Cell Biol Int ; 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36116024

RESUMO

MyoD family inhibitor (MDFI) is a myogenic transcription factor regulatory protein. MDFI has been proven to be upregulated and to promote cell proliferation in colorectal cancer. However, the role of MDFI in gastric cancer (GC) is unclear. In this study, MDFI expression in GC tissues and cell lines was examined by quantitative real-time PCR and western blot. Cell Counting Kit-8 assay, clone formation assay, and 5-ethynyl-2'-deoxyuridine assay were used to evaluate GC cell proliferation. Glycolysis was assessed by measuring glucose consumption and lactate and ATP production using commercial assay kits. Western blot was used to detect the expression levels of glycolytic key proteins and Wnt/ß-catenin pathway proteins. To activate Wnt/ß-catenin signaling, GC cells were treated with CHIR-99021. We found that MDFI expression was increased in GC tumor tissues and cells with a positive correlation with poor survival. Knockdown of MDFI inhibited the increase in GC cell proliferation and glycolysis induced by Helicobacter pylori. Helicobacter pylori infection promoted MDFI expression and activated Wnt/ß-catenin signaling. What is more, activation of the Wnt/ß-catenin pathway remarkably reversed the effect of knocking down MDFI on GC cells. Further studies found that MDFI participated in GC cell proliferation and glycolysis by regulating the Wnt/ß-catenin pathway, thereby affecting the development of GC. In conclusion, we demonstrated for the first time that knockdown of MDFI inhibited the increase in GC cell proliferation and glycolysis by regulating the Wnt/ß-catenin pathway. MDFI may be a new target for the clinical treatment of GC.

5.
Int J Mol Sci ; 23(17)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36077125

RESUMO

ROPs (Rho-like GTPases from plants) belong to the Rho-GTPase subfamily and serve as molecular switches for regulating diverse cellular events, including morphogenesis and stress responses. However, the immune functions of ROPs in Solanum lycopersicum Linn. (tomato) is still largely unclear. The tomato genome contains nine genes encoding ROP-type small GTPase family proteins (namely SlRop1-9) that fall into five distinct groups as revealed by phylogenetic tree. We studied the subcellular localization and immune response induction of nine SlRops by using a transient overexpression system in Nicotiana benthamiana Domin. Except for SlRop1 and SlRop3, which are solely localized at the plasma membrane, most of the remaining ROPs have additional nuclear and/or cytoplasmic distributions. We also revealed that the number of basic residues in the polybasic region of ROPs tends to be correlated with their membrane accumulation. Though nine SlRops are highly conserved at the RHO (Ras Homology) domains, only seven constitutively active forms of SlRops were able to trigger hypersensitive responses. Furthermore, we analyzed the tissue-specific expression patterns of nine ROPs and found that the expression levels of SlRop3, 4 and 6 were generally high in different tissues. The expression levels of SlRop1, 2 and 7 significantly decreased in tomato seedlings after infection with Ralstonia solanacearum (E.F. Smith) Yabuuchi et al. (GMI1000); the others did not respond. Infection assays among nine ROPs showed that SlRop3 and SlRop4 might be positive regulators of tomato bacterial wilt disease resistance, whereas the rest of the ROPs may not contribute to defense. Our study provides systematic evidence of tomato Rho-related small GTPases for localization, immune response, and disease resistance.


Assuntos
Lycopersicon esculentum , Proteínas Monoméricas de Ligação ao GTP , Ralstonia solanacearum , Resistência à Doença/genética , Lycopersicon esculentum/genética , Lycopersicon esculentum/metabolismo , Proteínas Monoméricas de Ligação ao GTP/genética , Filogenia , Ralstonia solanacearum/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo
6.
Front Pharmacol ; 13: 952482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071851

RESUMO

Sorafenib resistance is often developed and impedes the benefits of clinical therapy in hepatocellular carcinoma (HCC) patients. However, the relationship between sorafenib resistance and tumor immune environment and adjuvant drugs for sorafenib-resistant HCC are not systemically identified. This study first analyzed the expression profiles of sorafenib-resistant HCC cells to explore immune cell infiltration levels and differentially expressed immune-related genes (DEIRGs). The prognostic value of DEIRGs was analyzed using Cox regression and Kaplan-Meier analysis based on The Cancer Genome Atlas. The primary immune cells infiltrated in sorafenib-resistant HCC mice were explored using flow cytometry (FCM). Finally, small-molecule drugs for sorafenib-resistant HCC treatment were screened and validated by experiments. The CIBERSORT algorithm and mice model showed that macrophages and neutrophils are highly infiltrated, while CD8+ T cells are downregulated in sorafenib-resistant HCC. Totally, 34 DEIRGs were obtained from sorafenib-resistant and control groups, which were highly enriched in immune-associated biological processes and pathways. NR6A1, CXCL5, C3, and TGFB1 were further identified as prognostic markers for HCC patients. Finally, nalidixic acid was identified as a promising antagonist for sorafenib-resistant HCC treatment. Collectively, our study reveals the tumor immune microenvironment changes and explores a promising adjuvant drug to overcome sorafenib resistance in HCC.

7.
Int J Anal Chem ; 2022: 6970747, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36065393

RESUMO

A simple, rapid, and convenient method for the determination of neomycin based on the ion association method was proposed. In Britton-Robinson buffer solution, neomycin could react with Congo red to form an ionic association, which in turn reacted with dodecyl trimethyl ammonium bromide to form a ternary ionic association. The three were combined in a 1 : 1 : 1 ratio, which significantly enhanced the resonant Rayleigh scattering intensity at 468 nm. The obtained resonant Rayleigh scattering sensor showed a linear relationship with neomycin in the range of 0.07∼1 µg·mL-1. The limit of detection was 0.02 µg·mL-1, and the limit of quantification was 0.037 µg·mL-1. The experimental conditions were optimized. The method was verified based on the ICH rule. The established method could be applied to the analysis of the acceptable recovery rate of neomycin in powdered veterinary drugs.

8.
J Appl Gerontol ; : 7334648221124915, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36070289

RESUMO

Using data from 2015 to 2018 waves of the Longitudinal Study of Older Adults in Anhui Province, China, this study investigated associations between different forms of social disconnectedness (social isolation, loneliness, living alone) and psychological well-being of older adults longitudinally. The results showed that social isolation and loneliness were independently associated with psychological well-being, whereas living alone was not. Different forms of social disconnectedness had additive and interactive effects on psychological well-being of older adults. Those who were exposed to all three forms of social disconnectedness suffered from the lowest level of psychological well-being. Moreover, the adverse effects of social disconnectedness on psychological well-being were found to be stronger for older women than for older men. The results underscore the necessity to consider multiple forms of social disconnectedness as well as their different combinations in explaining psychological well-being in later life.

9.
Nat Commun ; 13(1): 5153, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36055986

RESUMO

Seasonal biases (the warm-season contribution) of Holocene mean annual temperature (MAT) reconstructions from geological records were proposed as a possible cause of the mismatch with climate simulated temperature. Here we analyze terrestrial mollusk assemblages that best reflect seasonal signals and provide quantitative MAT and four-season temperature records for northern China during the past 20,000 years. The MAT estimated from the seasonal temperatures of a four-season-mean based on mollusks shows a peak during ~9000-4000 years ago, followed by a cooling trend. In general, the contribution of summer and winter temperature to MAT is significantly greater than that of spring and autumn temperatures. The relative contribution of each season varies over time and corresponds roughly with the seasonal insolation in each season. This independent evidence from mollusk records from the mid-latitudes of East Asia does not support the Holocene long-term warming trend observed in climate simulations and the seasonal bias explanation.


Assuntos
Clima , Moluscos , Animais , Extremo Oriente , Estações do Ano , Temperatura
10.
Biomed Res Int ; 2022: 8453697, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046458

RESUMO

Objective: To research the influence of PDCA (Plan-Do-Check-Act) process management on the incidence of needle injury and psychological anxiety of nursing interns. Methods: This study belonged to the experimental study. A total of 180 nursing interns who practiced in the hospital from March 2020 to April 2022 were studied. A total of 135 interns from March 2020 to March 2021 were selected as the control group and 175 interns from April 2021 to April 2022 as the research group. PDCA process management was carried on in the research group. The control group did not make any intervention only following the routine teaching plan. The incidence of needle injury, theoretical knowledge, behavior score, self-rating anxiety scale (SAS), professional self-efficacy questionnaire score, and nursing practice satisfaction score were evaluated before and after 12 months of management. Results: After management, the incidence of needle injury in the research group was lower compared to that in the control group, and there are statistically significant differences between groups (P < 0.05). The scores of theoretical knowledge, attitude, and behavior in the research group were higher compared to those in the control group, and there are statistically significant differences between groups (P < 0.05) after management. After 12 months of management, the SAS score of the research group was lower compared to that of the control group, and there are statistically significant differences between groups (P < 0.05). The score of occupational self-efficacy questionnaire in the research group was higher compared to that in the control group, and there are statistically significant differences between groups (P < 0.05) after PDCA process management. After 12 months of management, the satisfaction score of nursing practice in the research group was higher compared to that in the control group, and there are statistically significant differences between groups (P < 0.05). Conclusion: Through PDCA process management, we can keep abreast of the situation of needlestick injuries among nursing students in practice and analyze in more detail the root cause of each nursing student's occupational exposure and the outcome of treatment. The nursing students not only learn more practical knowledge in clinical practice but also feel that the hospital values and cares for them, which greatly increases their satisfaction.


Assuntos
Ferimentos Penetrantes Produzidos por Agulha , Estudantes de Enfermagem , Ansiedade/epidemiologia , Humanos , Incidência , Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Inquéritos e Questionários
11.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4190-4201, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046910

RESUMO

The chemical components in rats after oral administration of the water extract of Chrysanthemum morifolium cv. Fubaiju(CMF) were analyzed by UPLC-Q-TOF-MS/MS technique. Forty-four compounds were identified from the water extract of CMF and 11 components were identified from the rat serum. A total of 264 potential anti-inflammatory targets were identified by network pharmacology based on serum components. The "component-target" network and protein-protein interaction(PPI) network were constructed, and GO function enrichment and KEGG pathway enrichment analyses were performed. The molecular docking was carried out to validate the results of network pharmacology. The results showed that CMF might act on AKT1, TNF, TP53, IL6, INS, and other core targets through apigenin, luteolin, acacetin, diosmetin, 3,4-O-dicaffeoylquinic acid, and other active components, and exert anti-inflammatory effects by regulating PI3 K-AKT signaling pathway, FoxO signaling pathway, cAMP signaling pathway, Ras signaling pathway, and other pathways. The pharmacodynamic materials basis of CMF was identified by UPLC-Q-TOF-MS/MS technology, and the core anti-inflammatory targets and the underlying mechanism of action were analyzed by network pharmacology and molecular docking, which provided a reference for comprehensively clarifying the pharmacodynamic materials basis and quality control of CMF.


Assuntos
Chrysanthemum , Medicamentos de Ervas Chinesas , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/química , Simulação de Acoplamento Molecular , Farmacologia em Rede , Ratos , Espectrometria de Massas em Tandem/métodos , Água
12.
Ying Yong Sheng Tai Xue Bao ; 33(9): 2521-2529, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36131669

RESUMO

China has entered the stage of rapid urbanization since the 1990s, resulting in a series of environmental problems. Based on the nighttime light remote sensing data and land use data from 1995 to 2020, we extracted the compound night light index (CNLI) to measure the urbanization level of mid-southern Liaoning urban agglomeration, evaluated habitat quality by InVEST model. We examined the relationship between urbanization level and habitat quality in mid-southern Liaoning urban agglomeration by using the correlation analysis method and the geographic weighted regression model. The results showed that CNLI increased by 0.14 from 1995 to 2020. The urbanization level increased continuously, with a pattern of "low in the east and high in the west". The habitat quality decreased by 0.005, showing a pattern of "high in the east and low in the west". The ecological environment became worse. There was a significant negative spatial correlation between urbanization level and habitat quality in mid-southern Liaoning urban agglomeration. The negative impact of urbanization level on habitat quality gradually decreased. In order to alleviate habitat degradation caused by urbanization and realize the coordinated and sustainable development of regional social economy, it was urgent to take a series of measures, such as delimiting the ecological protection red line, improving the intensive use of land, delimiting the urban boundary, promoting the coordinated development of regional integration.


Assuntos
Ecossistema , Urbanização , China , Cidades , Conservação dos Recursos Naturais , Meio Ambiente , Desenvolvimento Sustentável
13.
Biosensors (Basel) ; 12(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36140088

RESUMO

The cancer stem cells (CSC) are the roots of cancer. The CSC hypothesis may provide a model to explain the tumor cell heterogeneity. Understand the biological mechanism of CSC will help the early detection and cure of cancer. The discovery of the dynamic changes in CSC will be possible by the using of bio-engineering techniques-lineage tracing. However, it is difficult to obtain real-time, continuous, and dynamic live-imaging information using the traditional approaches that take snapshots of time points from different animals. The goal of molecular imaging is to monitor the in situ, continuous molecular changes of cells in vivo. Therefore, the most advanced bioengineering lineage tracing approach, while using a variety of molecular detection methods, will maximize the presentation of CSC. In this review, we first introduce the method of lineage tracing, and then introduce the various components of molecular images to dynamic detect the CSC. Finally, we analyze the current situation and look forward the future of CSC detection.

14.
Drug Deliv ; 29(1): 3052-3070, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36146939

RESUMO

Dihydromyricetin (DHM) is an important natural flavonoid that has attracted much attention because of its various functions such as protecting the cardiovascular system and liver, treating cancer and neurodegenerative diseases, and anti-inflammation effect, etc. Despite its great development potential in pharmacy, DHM has some problems in pharmaceutical applications such as low solubility, permeability, and stability. To settle these issues, extensive research has been carried out on its physicochemical properties and dosage forms to produce all kinds of DHM preparations in the past ten years. In addition, the combined use of DHM with other drugs is a promising strategy to expand the application of DHM. However, although invention patents for DHM preparations have been issued in several countries, the current transformation of DHM research results into market products is insufficient. To date, there is still a lack of deep research into the pharmacokinetics, pharmacodynamics, toxicology, and action mechanism of DHM preparations. Besides, preparations for combined therapy of DHM with other drugs are scarcely reported, which necessitates the development of dosage forms for this application. Apart from medicine, the development of DHM in the food industry is also of great potential. Due to its multiple effects and excellent safety, DHM preparations can be developed for functional drinks and foods. Through this review, we hope to draw more attention to the development potential of DHM and the above challenges and provide valuable references for the research and development of other natural products with a similar structure-activity relationship to this drug.

15.
Luminescence ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071675

RESUMO

Two simple, sensitive, and low-cost fluorescence spectroscopy methods for neomycin (NEO) detection were developed. Both methods are based on the interaction between NEO and Congo red (CR) in acidic buffer medium to form an ion-association complex. The quenching effect of the formed ion-association complex on the fluorescence of CR at 421 nm is the basic principle of fluorescence analysis, while the resonance Rayleigh scattering (RRS) method is used to enhance the resonance Rayleigh scattering spectrum at 384 nm by adding NEO. The experimental conditions such as pH, temperature, reaction time, CR concentration and ionic strength of two methods were investigated and optimized. In addition, the effect of common coexisting substances on the method was tested and the results showed good selectivity. And the composition of ion-association complexes, the reaction mechanism, and reasons for the enhanced intensity of RRS was discussed. Under optimum conditions, the responses of the fluorescence spectrophotometry and RRS methods showed good linearity with NEO concentrations in the range of 0.2-3.0 µg mL-1 and 0.1-3.0 µg mL-1 respectively. The detection limits of fluorescence spectrophotometry and RRS spectroscopy techniques were 0.02 µg mL-1 and 0.01 µg mL-1 , respectively. Finally, two methods were applied to the analysis of wastewater and the results were satisfactory.

16.
PLoS One ; 17(9): e0273434, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36083894

RESUMO

In this study, thirty-four soil samples from a typical chlor-alkali slag residue storage site near the city of Qiqihar in northeastern China were collected and their arsenic, cadmium, chromium, copper, mercury, nickel, lead and zinc concentrations were determined. Sources of these heavy metals were analyzed with a positive matrix factorization model, and the health risks associated with different pollution sources were calculated. The results showed that mercury was the main heavy metal pollutant at the site (maximum concentration of 112.19 mg.kg-1) and the soil was also contaminated with arsenic, copper and lead. The sources of eight heavy metals were: mixed oil refinery wastewater and parent material (arsenic, chromium, copper and lead), vinyl chloride waste source (mercury), parent material (cadmium, nickel and zinc). The average potential ecological risk of the soil was 22344.39, with vinyl chloride waste source contributing 99.85% of this risk. The average carcinogenic risk of a mixture of oil refinery wastewater and parent material for children and adults was 9.06×10-6 and 6.36×10-6, respectively, accounting for 99.9% (children) and 99.48% (adults) of the total average carcinogenic risk. The average hazard index of vinyl chloride waste source for children and adults was 0.6 and 0.38, respectively, which accounted for 64.13% (children) and 52.34% (adults) of the total hazard index. These results provide a reference for soil pollution risk assessments at this type of site.


Assuntos
Arsênio , Mercúrio , Metais Pesados , Poluentes do Solo , Cloreto de Vinil , Adulto , Álcalis , Arsênio/análise , Cádmio , Criança , China , Cromo , Cobre/análise , Monitoramento Ambiental/métodos , Humanos , Mercúrio/análise , Metais Pesados/análise , Níquel , Medição de Risco , Solo/química , Poluentes do Solo/análise , Águas Residuárias , Zinco
17.
Trials ; 23(1): 797, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131289

RESUMO

BACKGROUND: Depression and anxiety are common among pregnant women. Internet-delivered psychological therapies such as cognitive behavioral therapy (iCBT) have been developed to increase accessibility and address common help-seeking barriers, especially during pandemic period. The objective of this trial is to evaluate the short-term and long-term effects of iCBT on reducing depressive symptoms among pregnant women during the COVID-19 pandemic with the overall goal of preventing depression recurrence in the first 12 months postpartum. METHODS: A multi-site randomized controlled trial will be conducted where 300 pregnant women early in their third trimester will be screened for depression symptoms using the Edinburgh Postnatal Depression Scale (EPDS) during a routine obstetrical visit. Eligible and consenting women with a score greater than 9 will be randomly allocated (1:1) to either intervention group or control group. ICBT involving the completion of 7 weekly online modules will be delivered via a well-designed perinatal mental healthcare app. The primary objective is to evaluate the effect of iCBT on reducing depression symptoms among pregnant Chinese women starting from their third trimester. The secondary objectives are to examine the effect of iCBT on anxiety, sleep quality, social support, parenting stress, co-parenting relationship, and infant development. DISCUSSION: This multi-center randomized controlled trial has been planned in accordance with best practices in behavioral trial design. The internet-based intervention addressed the needs of pregnant women during a major pandemic where face-to-face therapy is not preferable. The trial has a relatively large sample size with sufficient power to evaluate the efficacy of iCBT intervention for the primary and secondary outcomes. One year follow-up evaluation in the study is designed to determine the longer-term effect of the intervention on both maternal and infant outcomes. Although a limitation is the assessment of depression and anxiety using self-report measures, these easily incorporated and maternal-preferred assessments allow for real-life scalability if the intervention is proven to be effective. ETHICS AND DISSEMINATION: Ethics was approved by the institutional review board of International Peace Maternity and Child Health Hospital (GKLW2020-25). Dissemination of results will be published in peer-reviewed academic journals and presented at scientific conferences. TRIAL STATUS: The first patient was enrolled on 19 August 2020. To date, 203 participants have met eligibility requirements and been randomized to either the intervention group or control group. Data collection aims to be complete in September 2022. Date and version identifier: 2020715-version1.0. TRIAL REGISTRATION: ChiCTR2000033433. Registered 31 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=54482 .


Assuntos
COVID-19 , Terapia Cognitivo-Comportamental , Criança , Terapia Cognitivo-Comportamental/métodos , Depressão/diagnóstico , Depressão/terapia , Feminino , Humanos , Internet , Estudos Multicêntricos como Assunto , Pandemias , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
Front Endocrinol (Lausanne) ; 13: 893238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147561

RESUMO

Hypothalamus-pituitary-adrenal (HPA) axis plays critical roles in stress responses under challenging conditions such as hypoxia, via regulating gene expression and integrating activities of hypothalamus-pituitary-targets cells. However, the transcriptional regulatory mechanisms and signaling pathways of hypoxic stress in the pituitary remain to be defined. Here, we report that hypoxia induced dynamic changes in the transcription factors, hormones, and their receptors in the adult rat pituitary. Hypoxia-inducible factors (HIFs), oxidative phosphorylation, and cAMP signaling pathways were all differentially enriched in genes induced by hypoxic stress. In the pituitary gene network, hypoxia activated c-Fos and HIFs with specific pituitary transcription factors (Prop1), targeting the promoters of hormones and their receptors. HIF and its related signaling pathways can be a promising biomarker during acute or constant hypoxia. Hypoxia stimulated the transcription of marker genes for microglia, chemokines, and cytokine receptors of the inflammatory response. Corticotropin-releasing hormone receptor 1 (CRHR1) mediated the transcription of Pomc, Sstr2, and Hif2a, and regulated the function of HPA axis. Together with HIF, c-Fos initiated and modulated dynamic changes in the transcription of hormones and their receptors. The receptors were also implicated in the regulation of functions of target cells in the pituitary network under hypoxic stress. CRHR1 played an integrative role in the hypothalamus-pituitary-target axes. This study provides new evidence for CRHR1 involved changes of hormones, receptors, signaling molecules and pathways in the pituitary induced by hypoxia.

19.
Environ Pollut ; 312: 120092, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36064063

RESUMO

To date, knowledge of internal human exposure to BPA and its analogues (particularly bisphenol S and bisphenol F, etc.) remains limited. In the present study, a method involving dispersive solid-phase extraction and LC/MS was proposed to investigate the contamination levels of 28 precursor bisphenols and 9 major metabolites in serum. The critical variables of preparation method were screened out by Plackett-Burman design and further optimized by central composite design. Left in optimal conditions, a total of 286 samples consisting of 153 males and 133 females were analyzed. The results showed that BPA dominated over all the cases with the highest positive rate (82.2% of all the surveyed people), and totally four metabolites (BPA ß-D-glucuronide, BPA monosulfate, BPA bis-(ß-D-glucuronide) and BPS monosulfate) were detectable. The occurrence of BPA bis-(ß-D-glucuronide) in serum is reported for the first time and its higher positive rate and contamination concentrations suggested that it may be a more important metabolite of BPA than others. Negligible potential risk of health effects to blood donors was observed, since the estimated exposure levels (mean 32.1 ng/kg bw/day, 95th 123.2 ng/kg bw/day) were well below far less than the temporary tolerable reference dose of BPA that recommended by the European Food Safety Authority (4 µg/kg bw/day by). The reference level of BPA for healthy population was determined to be 4.09 µg/L via the percentile method.

20.
Front Pharmacol ; 13: 990505, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059964

RESUMO

Nanoparticles based on single-component synthetic polymers, such as poly (lactic acid-co-glycolic acid) (PLGA), have been extensively studied for antitumor drug delivery and adjuvant therapy due to their ability to encapsulate and release drugs, as well as passively target tumors. Amphiphilic block co-polymers, such as polyethylene glycol (PEG)-PLGA, have also been used to prepare multifunctional nanodrug delivery systems with prolonged circulation time and greater bioavailability that can encapsulate a wider variety of drugs, including small molecules, gene-targeting drugs, traditional Chinese medicine (TCM) and multi-target enzyme inhibitors, enhancing their antitumor effect and safety. In addition, the surface of PEG-PLGA nanoparticles has been modified with various ligands to achieve active targeting and selective accumulation of antitumor drugs in tumor cells. Modification with two ligands has also been applied with good antitumor effects, while the use of imaging agents and pH-responsive or magnetic materials has paved the way for the application of such nanoparticles in clinical diagnosis. In this work, we provide an overview of the synthesis and application of PEG-PLGA nanoparticles in cancer treatment and we discuss the recent advances in ligand modification for active tumor targeting.

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