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1.
Eur J Pharmacol ; 912: 174613, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740581

RESUMO

Pulmonary fibrosis (PF) is a chronic, progressive heterogeneous disease of lung tissues with poor lung function caused by scar tissue. Due to our limited understanding of its mechanism, there is currently no treatment strategy that can prevent the development of PF. In recent years, iron accumulation and mitochondrial damage have been reported to participate in PF, and drugs that reduce iron content and improve mitochondrial function have shown significant efficacy in animal experimental models. Excessive iron leads to mitochondrial impairment, which may be the key cause that results in the dysfunction of various kinds of pulmonary cells and further promotes PF. As an emerging research hotspot, there are few targeted effective therapeutic strategies at present due to limited mechanistic understanding. In this review, the roles of iron homeostasis imbalance and mitochondrial damage in PF are summarized and discussed, highlighting a promising direction for finding truly effective therapeutics for PF.

2.
Chemosphere ; : 132825, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34762875

RESUMO

Prothioconazole (PTC) is a high effective systemic fungicide, and one of its major metabolites is prothioconazole-desthio (PTC-d). Because of its wildly use in the farmland of China, the local eco-toxicological effects of PTC as well as PTC-d are needed to be concerned. This study investigated hepatoxicity of Chinese lizards (Eremias argus), a local non-target organism, after single dose oral treated (100 mg kg-1 BW) through pathological, enzyme activity and gene expression analysis. PTC treatment caused ballooning and PTC-d treatment led to macrovesicular steatosis of hepatocyte. The elevation of serum indexes, including the activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT), further confirmed the hepatic injury. PTC and PTC-d treatments altered oxidative status reflected by the inhibition of superoxide dismutase (SOD) activity , meanwhile, the stimulation of catalase (CAT) activity, glutathione peroxidase (GPx) activity and malondialdehyde (MDA) content. The mRNA expression changes of apoptosis-related factors and cytokines genes, including Bax, Bcl-2, TNF-α, NF-κB, Caspase-3 and Nrf2, deeply uncovered the potential mechanism of hepatotoxicity caused by PTC and PTC-d. In brief, the results indicated that both of these two compounds altered oxidative status, then were likely to trigger caspase-3 by affecting the ratio of pro- and anti-apoptotic factors which belong to intrinsic apoptosis pathway. Specifically, more serious impacts were induced by PTC-d than its parent compound. This study is the first to provide specific insight into potential hepatotoxicity resulted from PTC and PTC-d in male Chinese lizards.

3.
Sci Total Environ ; : 151773, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34808164

RESUMO

Reptiles are sensitive to temperature changes as ectotherm animals. The climate warming may pose more serious threat to reptiles. Although the behavior effect and reproduction biology have been well studied, little information is available about the adaptation mechanisms of reptiles to temperature stress. In this study, the native Chinese species, Eremias argus were incubated at 15 (cold stress), 25 (control group) and 35 °C (thermal stress) for 24 h. The transcriptome and metabolome technology were applied to investigate the molecular regulation mechanisms of lizards to acute temperature changes. The CIRBP and HSPA8 were hub genes in response to temperature adaptation. The increased expression of PER gene in lizard circadian rhythm is associated with tyrosine metabolism after cold or thermal stress. The poly-unsaturated fatty acids in female lizard liver were significantly increased with up-regulation of FASN and ACACA genes after thermal stress, which proved the disruption of fatty acid biosynthesis pathway in corporation with the altered body weight. The cortisol and testosterone were important steroid hormones in response to temperature changes especially in male lizard liver. The increased CIRBP gene expression in lizard gonads suppressed the KDM6B gene, which regulates the testis development and may induce sex reversal in male lizard after thermal stress. The adaptation responses of lizards to temperature stress may threaten the health status of wild population.

4.
Inflammation ; 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837126

RESUMO

Ferritin, which is composed of a heavy chain and a light chain, plays a critical role in maintaining iron homeostasis by sequestering iron. The ferritin light chain (FTL) is responsible for the stability of the ferritin complex. We have previously shown that overexpression of FTL decreases the levels of the labile iron pool (LIP) and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-treated murine macrophage cells. The protein level of FTL was downregulated by LPS within a short treatment period. However, the mechanism underlying the LPS-induced changes in the FTL levels is not known. In the present study, we report that LPS induces the ubiquitin-proteasome-dependent degradation of FTL and that the mechanism of LPS-induced FTL degradation involves the JNK/Itch axis. We found that LPS downregulates the protein and mRNA levels of FTL in a time-dependent manner. The proteasome inhibitor MG-132 significantly reverses the LPS-induced decrease in FTL. Furthermore, we observed that LPS treatment cannot cause ubiquitination of the lysine site (K105 and K144) mutant of FTL. Interestingly, LPS-mediated ubiquitin-dependent degradation of FTL is significantly inhibited by the JNK-specific inhibitor SP600125. Moreover, LPS could upregulate the protein level of E3 ubiquitin ligase Itch, a substrate of JNK kinases. Immunoprecipitation analyses revealed an increase in the association of FTL with Itch, a substrate of JNK kinases, in response to LPS stimulation. SP600125 decreased LPS-induced Itch upregulation. Taken together, these results suggest that LPS stimulation leads to the degradation of FTL through the ubiquitin-proteasome proteolytic pathway, and this FTL degradation is mediated by the JNK/Itch axis in murine macrophage cells.

5.
Environ Pollut ; 293: 118460, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34748890

RESUMO

Thiamethoxam (TMX), a representative neonicotinoids, is widely used for seed coating. The consumption of TMX-coated seeds posed threat to birds during crop sowing. The hepatotoxicity of TMX has been reported in mammals, however, no clear evidence showed TMX-induced toxic effects on bird liver. In this study, male Japanese quails (Coturnix japonica) were exposed to 20 or 200 mg/kg TMX-treated bird feed for 28 days. Results showed that Clothianidin (CLO), a TMX metabolite preferred to accumulate in quail plasma and liver, and inflammatory cell infiltration was found in quail livers. Oxidative stress-related biological processes were significantly enriched in both TMX treatment groups through transcriptomics analysis. Moreover, integrative analysis of transcriptomics and metabolomics indicated ferroptosis and DNA damage was implicated in hepatotoxicity caused by high- and low-concentration of TMX exposure, respectively. High-dose TMX treatment decreased CAT activity and GSH concentration and increased expression of the ferroptosis-related gene. In addition, the up-regulation of 8-OHdG concentration and DNA repair-related genes expression demonstrated low-dose TMX triggered oxidative DNA damage. The present results highlight the toxicity of TMX to bird livers and contribute to a better understanding of the TMX toxic mechanism in birds.

6.
Eur J Med Res ; 26(1): 119, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34602082

RESUMO

BACKGROUND: For a patient presenting with fever, multiple lymphadenopathy and splenomegaly, pathogen infection should be preferentially considered, followed by lymphoid malignancies. When traditional laboratory and pathological detection cannot find the pathogenic microorganism, metagenomic sequencing (MGS) which targets the person's genome for exceptional genetic disorders may detect a rare pathogen. CASE PRESENTATION: Here, we introduced the diagnostic clue of a case of multicentric Castleman disease (MCD) with hemophagocytic syndrome which was elicited from the detection of human herpesvirus-8 in the blood of a HIV-1 infected person by MGS technology during pathogen inspection. This case highlights the need to increase the awareness of MCD among clinicians and pathologists. CONCLUSIONS: MGS technology may play a pivotal role in providing diagnostic clues during pathogen inspection, especially when pathogens are not detectable by conventional methods.

8.
Membranes (Basel) ; 11(10)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34677537

RESUMO

Ion-exchange membranes (IEMs) represent a key component in various electrochemical energy conversion and storage systems. In this study, electrochemical impedance spectroscopy (EIS) was used to investigate the effects of structural changes of anion exchange membranes (AEMs) on the bulk membrane and interface properties as a function of solution pH. The variations in the physico/electrochemical properties, including ion exchange capacity, swelling degree, fixed charge density, zeta potentials as well as membrane and interface resistances of two commercial AEMs and cation exchange membranes (CEMs, as a control) were systematically investigated in different pH environments. Structural changes of the membrane surface were analyzed by Fourier transform infrared and X-ray photoelectron spectroscopy. Most notably, at high pH (pH > 10), the membrane (Rm) and the diffusion boundary layer resistances (Rdbl) increased for the two AEMs, whereas the electrical double layer resistance decreased simultaneously. This increase in Rm and Rdbl was mainly attributed to the deprotonation of the tertiary amino groups (-NR2H+) as a membrane functionality. Our results show that the local pH at the membrane-solution interface plays a crucial role on membrane electrochemical properties in IEM transport processes, particularly for AEMs.

9.
J Clin Med ; 10(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34640449

RESUMO

BACKGROUND: The performance of chest radiography-based age and sex prediction has not been well validated. We used a deep learning model to predict the age and sex of healthy adults based on chest radiographs (CXRs). METHODS: In this retrospective study, 66,643 CXRs of 47,060 healthy adults were used for model training and testing. In total, 47,060 individuals (mean age ± standard deviation, 38.7 ± 11.9 years; 22,144 males) were included. By using chronological ages as references, mean absolute error (MAE), root mean square error (RMSE), and Pearson's correlation coefficient were used to assess the model performance. Summarized class activation maps were used to highlight the activated anatomical regions. The area under the curve (AUC) was used to examine the validity for sex prediction. RESULTS: When model predictions were compared with the chronological ages, the MAE was 2.1 years, RMSE was 2.8 years, and Pearson's correlation coefficient was 0.97 (p < 0.001). Cervical, thoracic spines, first ribs, aortic arch, heart, rib cage, and soft tissue of thorax and flank seemed to be the most crucial activated regions in the age prediction model. The sex prediction model demonstrated an AUC of >0.99. CONCLUSION: Deep learning can accurately estimate age and sex based on CXRs.

10.
BMC Gastroenterol ; 21(1): 395, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686147

RESUMO

BACKGROUND: Patients with primary biliary cholangitis (PBC) often have comorbid dyslipidemia, and determining the degree of hepatic steatosis can help predict the risk of cardiovascular events in PBC patients. The aim of our study was to analyze the characteristics of lipid distribution and the degree of hepatic steatosis in PBC. METHODS: We retrospectively analyzed 479 cases of PBC, chronic hepatitis B (CHB), chronic hepatitis C (CHC), non-alcoholic fatty liver disease (NAFLD), and healthy subjects (Normal) diagnosed by liver biopsy or definitive clinical diagnosis. Controlled attenuation parameter (CAP) values were applied to assess the degree of steatosis of the liver, and lipid levels were also compared in the five cohorts. RESULTS: We found that among the five groups of subjects, the PBC group had the lowest CAP values (P < 0.001), and the high-density lipoprotein cholesterol (HDL-C) level in the PBC group was higher than normal, CHC and CHB group (P = 0.004, P = 0.033, P < 0.001, respectively).In the multivariate linear analysis, only BMI (ß = 1.280, P = 0.028), ALP (ß = - 0.064, P = 0.012), TBA (ß = - 0.126, P = 0.020), TG (ß = 12.520, P = 0.000), HDL-C (ß = - 11.338, P = 0.001) and LDL-C (ß = 7.012, P = 0.002) were independent predictors of CAP. CONCLUSIONS: Among PBC, CHB, CHC, NAFLD and healthy subjects, PBC had the lowest degree of hepatic steatosis and higher HDL-C levels, all of which were found to be protective factors against atherosclerosis and cardiovascular risk and would provide a valuable reference for the risk of developing cardiovascular events in PBC patients.


Assuntos
Cirrose Hepática Biliar , Hepatopatia Gordurosa não Alcoólica , HDL-Colesterol , Humanos , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Retrospectivos
11.
Arch Gerontol Geriatr ; 98: 104544, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34628214

RESUMO

BACKGROUND: Frailty has been proposed as a poor prognostic indicator for elderly patients with coronary artery diseases (CAD). The objective of this meta-analysis was to evaluate the effects of frailty on all-cause mortality in elderly patients with CAD following percutaneous coronary intervention (PCI). METHODS: PubMed, Embase, the Cochrane library, Web of science, and ClinicalTrial.gov were searched for associated studies from their inception to April 30, 2021. Odds ratios (OR) were calculated to estimate the in-hospital and short-term outcomes, whereas the hazard ratios (HR) were pooled for long-term mortality using random-effects by Revman 5.3. RESULTS: A total of nine studies including 2658 elderly participants were included in this meta-analysis. It was identified that the prevalence of frailty ranged from 12.5 to 27.8%. Frailty was associated with increased in-hospital mortality (OR 3.59, 95% CI 2.01 - 6.42; I2 = 35%), short-term mortality (OR 6.61, 95% CI 2.89 - 15.16; I2 = 0%), as well as long-term mortality (HR 3.24, 95% CI 2.04- 5.14; I2 = 70%) in patients undergoing PCI. Besides, we also found that prefrailty was a predictor of all-cause mortality. CONCLUSIONS: Frailty was associated with in-hospital, short-term and long-term mortality in elderly patients with PCI. The results may consolidate the importance of routine frailty screening in risk stratification in elderly patients with CAD who are considered for PCI.

12.
Rapid Commun Mass Spectrom ; : e9199, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554614

RESUMO

RATIONALE: The objective of this study was to develop, optimize, and validate a method for the determination and quantification of 17 hypoglycemic drugs in fingerprints using ultra-high-performance liquid chromatography-tandem hybrid triple quadrupole linear ion trap mass spectrometry (UHPLC-QTRAP-MS/MS). We also aimed to apply the present method to the fingerprints collected from patients with hyperglycemia. METHODS: The scheduled multiple reaction monitoring-information dependent acquisition-enhanced product ion (SMRM-IDA-EPI) scanning mode was utilized. The chromatographic system consisted of an Acquity UHPLC® BEH C18 column (3.0×100 mm, 1.7µm) and a mobile phase of 0.01% (v/v) formic acid in water and methanol. Analytes were extracted via a precipitation protein procedure. The method was validated in accordance with the US food and drug administration (FDA) guidance and applied to the analysis of fingerprint deposits from subjects who have taken the drugs. RESULTS: The limits of detection (LODs) and the lower limits of quantification (LLOQs) of 17 hypoglycemic drugs were 0.001 to 0.020 and 0.002 to 0.050 ng/fingerprint, respectively. The correlation coefficients (r) for the calibration curves were > 0.99 in the range of 0.050-50.000 ng/fingerprint. The matrix effect and recovery of 17 hypoglycemic drugs at three concentrations ranged from 81.1 to 117.3% and 80.0 to 109.6%, respectively. The validation data (intra- and inter-day combined) for accuracy ranged from 85.5 to 117.2%, the CV (%) data were ≤ 19.7%. All analytes were found to be stable stored in the autosampler (4°C) for 24 h. This validated method was successfully applied to detect hypoglycemic drugs in fingerprints from patients with hyperglycemia. CONCLUSIONS: A quantification method for hypoglycemic drugs in fingerprints was developed, optimized, and validated. This sensitive method could be used for drug monitoring and providing reference information in forensic investigations.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34550376

RESUMO

AIMS: Underuse of oral anticoagulants (OACs) is commonly observed among patients with atrial fibrillation (AF), which hinders stroke prevention in AF. Shared decision-making (SDM) can help enhance adherence by minimizing patients' misunderstanding of treatment and aligning care with their preferences. Decision aids (DAs) have been developed to facilitate the SDM process. This study aimed to: (i) evaluate the effects of DAs on AF patients' knowledge, decisional conflict, OAC uptake, and adherence and on the incidence of stroke and bleeding; and (ii) explore characterizing factors associated with enhanced DA effectiveness. METHODS AND RESULTS: Five databases were searched. Meta-analysis was conducted using RevMan 5.3 when data were available. Comparative analysis between effective and ineffective DAs was conducted to determine the DA designs associated with better effects. Ten studies were included. Pooling results indicated that DAs reduce decisional conflict related to warfarin use [mean difference = -0.10; 95% confidence interval (CI): -0.18 to -0.02; P = 0.01] and enhance OAC uptake [risk ratio: 1.03; 95% CI: 1.01-1.05; P = 0.004]. The effects of DAs on adherence and incidence of stroke and bleeding were unclear. Comparative analysis revealed that DAs with key elements of SDM (situation diagnosis, choice awareness, option clarification, benefits and disadvantages, and patient's preference) and pre-consultation delivery are more likely to be effective in promoting SDM and OAC uptake. CONCLUSIONS: DAs are promising in promoting SDM and OAC uptake in patients with AF. The evidence on adherence and incidence of stroke and bleeding remains uncertain. More trials with rigorous study design and longer follow-up are necessary to obtain evidence.

14.
BMC Infect Dis ; 21(1): 750, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348692

RESUMO

BACKGROUND: An upper abdominal mass without tenderness often indicates a benign or malignant tumor once liver or spleen hyperplasia has been excluded. A lymphadenopathic mass from Talaromyces marneffei infection is rare. CASE PRESENTATION: We report the case of a 29-year-old human immunodeficiency virus (HIV) infected man who presented with an upper abdominal mass and without any symptoms related with infection. Histopathology and next-generation sequencing (NGS) following biopsy of the mass confirmed T. marneffei-infected lymphadenopathy, and the patient was successfully treated with amphotericin B and itraconazole. CONCLUSIONS: This case report suggests that potential fungal infection should be considered during the diagnostic workup of a mass in clinical practice.


Assuntos
Linfadenopatia , Micoses , Talaromyces , Abdome/diagnóstico por imagem , Adulto , Antifúngicos/uso terapêutico , Humanos , Linfadenopatia/tratamento farmacológico , Masculino , Micoses/diagnóstico , Micoses/tratamento farmacológico , Talaromyces/genética
15.
Protein Sci ; 30(10): 2083-2091, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34382282

RESUMO

The chlorophyll biosynthesis regulator GENOMES UNCOUPLED 4 (GUN4) is conserved in nearly all oxygenic photosynthetic organisms. Recently, GUN4 has been found to be able to bind the linear tetrapyrroles (bilins) and stimulate the magnesium chelatase activity in the unicellular green alga Chlamydomonas reinhardtii. Here, we characterize GUN4 proteins from Arabidopsis thaliana and the cyanobacterium Synechocystis sp. PCC 6803 for their ability to bind bilins, and present the crystal structures of Synechocystis GUN4 in biliverdin-bound, phycocyanobilin-bound, and phytochromobilin-bound forms at the resolutions of 1.05, 1.10, and 1.70 Å, respectively. These linear molecules adopt a cyclic-helical conformation, and bind more tightly than planar porphyrins to the tetrapyrrole-binding pocket of GUN4. Based on structural comparison, we propose a working model of GUN4 in regulation of tetrapyrrole biosynthetic pathway, and address the role of the bilin-bound GUN4 in retrograde signaling.

16.
World J Clin Cases ; 9(18): 4803-4809, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34222451

RESUMO

BACKGROUND: Cutaneous myiasis is frequently observed; however, eosinophilic pleural effusion induced by this condition is rare. CASE SUMMARY: We report the case of a 65-year-old female Tibetan patient from Qinghai Province, who presented to West China Hospital of Sichuan University around mid-November 2011 with a chief complaint of recurrent cough, occasional hemoptysis, and right chest pain. There was no past medical and surgical history of note, except for occasional dietary habit of eating raw meat. Clinical examination revealed a left lung collapse and diminished breathing sounds in her left lung, with moist rales heard in both lungs. Chest X-rays demonstrated a left hydropneumothorax and a right lung infection. Chest computed tomography revealed a left hydropneumothorax with partial compressive atelectasis and patchy consolidation on the right lung. Laboratory data revealed peripheral blood eosinophilia of 37.2%, with a white blood cell count of 10.4 × 109/L. Serum immunoglobulin E levels were elevated (1650 unit/mL). Serum parasite antibodies were negative except for cysticercosis immunoglobulin G. Bone marrow aspirates were hypercellular, with a marked increase in the number of mature eosinophils and eosinophilic myelocytes. An ultrasound-guided left-sided thoracentesis produced a yellow-cloudy exudative fluid. Failure to respond to antibiotic treatment during hospitalization for her symptoms and persistent blood eosinophilia led the team to start oral albendazole (400 mg/d) for presumed parasitic infestation for three consecutive days after the ninth day of hospitalization. Intermittent migratory stabbing pain and swelling sensation on both her upper arms and shoulders were reported; tender nodules and worm-like live organisms were observed in the responding sites 1 wk later. After the removal of the live organisms, they were subsequently identified as first stage hypodermal larvae by the Sichuan Institute of Parasites. The patient's symptoms were relieved soon afterwards. Telephonic follow-up 1 mo later indicated that the blood eosinophilia and pleural effusion were resolved. CONCLUSION: Eosinophilic pleural fluid can be present in a wide array of disorders. Myiasis should be an important consideration for the differential diagnosis when eosinophilic pleural effusion with blood eosinophilia is observed.

17.
Se Pu ; 39(3): 271-280, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-34227308

RESUMO

Enantiomers are ubiquitous in nature, and they are especially important in the field of pharmaceutical chemistry. Although the enantiomers of chiral drugs have identical chemical structures, they differ notably in their pharmacological, toxicological, pharmacokinetic, metabolic, and other biological activities. The same is true for amphetamines, ketamine, and cathinones, as the chiral separation of these three drugs is representative of drugs. Gas chromatography (GC), high performance liquid chromatography (HPLC), and capillary electrophoresis (CE) are widely used for the chiral separation of these three kinds of drugs. There are some similarities among the three methods for the chiral separation of amphetamines, ketamine, and cathinones: n-trifluoroacetyl-L-prolinyl chloride and (+)R-α-methoxy-α-trifluoromethylphenylacetic acid are the two typical chiral derivatization reagents used in GC. In HPLC, three kinds of chiral stationary phases are used: proteins, polysaccharides, and macrocyclic antibiotics. Cyclodextrin and its derivatives are most commonly used in CE. However, these three methods have inherent shortcomings. In the case of GC, impurities produced during chiral derivatization may interfere with the analysis, and high reaction temperatures affect the efficiency of chiral separation. HPLC has limited application scope and is expensive. In CE, there has no established process to determine the appropriate chiral selector. In recent years, research into application of the chiral separation of the above-mentioned three kinds of drugs has its own characteristics in forensic toxicology. The chiral separation of amphetamine drugs is mostly used to infer the prototype and synthesis route of drugs on the market. The chiral separation of ketamine involves a variety of biological samples. For cathinones, chiral separation methods emphasize their wide applicability. In this review, 66 reports published in professional local and overseas magazines during the past decade are collated. The characteristics of the enantiomers of amphetamines, ketamine, and cathinones as well as the mechanism of chiral recognition are briefly introduced. The commonness of the research and the application of chiral separation in forensic toxicology are reviewed. This paper proposes that the chiral separation of drugs can be further investigated from the following three aspects: 1) the use of computer technology to establish a molecular model for exploring the mechanism of chiral recognition; 2) developing new technologies for chiral separation and carrying out commercial research on the supercritical fluid method; 3) applying chiral separation to judicial practice, pharmaceutical research and development, and other practical fields.


Assuntos
Alcaloides , Anfetaminas/isolamento & purificação , Ketamina , Alcaloides/isolamento & purificação , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Eletroforese Capilar , Ketamina/isolamento & purificação , Estereoisomerismo
18.
Biomaterials ; 276: 121010, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34247042

RESUMO

Immunosuppressive tumor microenvironment and low delivery efficiency severely impede the tumor chemotherapy effect. To address this issue, we develop a pH/ROS cascade-responsive prodrug micelle to deliver siTGF-ß with size-shrinkage and charge-reversal property, leading to synergistical tumor microenvironment remodeling. The nanosystem highly improved endocytosis efficiency and tumor penetration depth through charge reversal and size reduction upon exposure to weakly acidic tumor microenvironment. Moreover, the nanocarrier would rapidly escape from endo/lysosome, disassemble and release siTGF-ß and hydroxycamptothecin in response to high intracellular ROS. Furthermore, the nanosystem significantly boosted antitumor immune response and reduced immune tolerance with remodeling tumor microenvironment, which significantly prolonged the survival time of tumor-bearing mice (75% survival rate upon 35 days). It is realized by the combined effects of chemotherapy-enhanced immunogenicity and recruitment of effector T cells, TGF-ß-blockade immunotherapy-activated inhibition immunosuppressive tumor microenvironment and epithelial-to-mesenchymal transition (EMT), and regulation physical tumor microenvironment via reducing the dense tumor extracellular matrix and the high tumor interstitial pressure obstacles. To this end, the nanosystem not only overcame biobarriers and reinforced antitumor immune response, but also effectively inhibited tumor growth, metastasis and recurrence in vivo.


Assuntos
Imunoterapia , Nanopartículas , Fator de Crescimento Transformador beta/antagonistas & inibidores , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Concentração de Íons de Hidrogênio , Camundongos , Micelas , Espécies Reativas de Oxigênio
19.
Chemosphere ; 285: 131456, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34256203

RESUMO

Nowadays, the emergence of pesticides and its application in agriculture greatly improved the crop quality and food production. However, the resulted ecological problem caused by the widespread pesticide residues attracted more and more attention since the pesticides were harmful to most living organisms. Regulatory agencies such as Environmental Protection Agency (EPA) and European Chemicals Agency (ECHA) stipulated that a comprehensive pesticides risk assessment was essential and also underscored the application of computation method in evaluating pesticides. The present study aimed to use the Quantitative Structure-Activity Relationship (QSAR) method to establish models for quantitatively and qualitatively predicting the toxicity of pesticide against Skeletonema costatum. The regression model was developed using the Genetic Algorithm plus Multiple Linear Regression method and the classification model was established based on the Random Forest algorithm, respectively. Various internal and external validation metrics suggested that the obtained regression model was of good fitness (R2=0.722), robustness (QLOO2=0.653) and external predictive ability (QFn2:0.719-0.776, CCC = 0.878). The classification could correctly predict 79.4% of pesticides in the training set and 69.7% in the validation set. The relatively high sensitivity value of the classification model indicated its good performance in identifying high-toxic pesticides. It could be concluded from the selected modelling descriptors that molecular weight and polarizability impacted the toxicity the most. The atom-type E-state descriptors generally contributed negatively to the pesticide toxicity which verified the negative influence of molecular hydrophilicity. Moreover, the lipophilic, carbon-type, charge related descriptors demonstrated the important influence of lipophilicity and polarity on pesticide toxicity. The models presented in this work could be used to pre-evaluate the toxicity of pesticides within the applicability domain, thus focusing resources on the high-toxic pesticides and assessing the environmental risk of pesticides quickly and economically.


Assuntos
Praguicidas , Relação Quantitativa Estrutura-Atividade , Algoritmos , Modelos Lineares , Praguicidas/toxicidade
20.
Geriatr Nurs ; 42(5): 1019-1023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34256150

RESUMO

This study examined whether and to what extent sleep disturbance mediates the effects of depressive symptoms on the cognition of individuals with mild cognitive impairment (MCI), who represent a high-risk group for developing dementia. Cross-sectional data were obtained from a sample of 204 Chinese community-dwelling older adults with MCI. MCI subjects were screened using the Montreal Cognitive Assessment, sleep quality was measured using the Pittsburgh Sleep Quality Index, and depressive symptoms were assessed using the Geriatric Depression Scale. Mediation analysis was conducted using the PROCESS macro with 10,000 bootstrap samples. The significant mediating effect of sleep quality on the association between depressive symptoms and cognition (Beta = -0.025; 95% CI, -0.054 to -0.007) explains 26% of the total effect of depressive symptoms on cognition and implies that the timely detection and management of sleep disturbance among the MCI population is highly important, especially for those with depressive symptoms.


Assuntos
Disfunção Cognitiva , Depressão , Idoso , Cognição , Estudos Transversais , Depressão/epidemiologia , Humanos , Sono
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