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1.
Chronobiol Int ; : 1-7, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632893

RESUMO

Modern lifestyles, and the popularization of artificial light at night, have led to maladjusted social time and internal circadian rhythm, so developing an instrument on biological rhythms is critical. A 36-item self-rated questionnaire assessing biological rhythm disorder in adolescents was developed according to the literature and expert evaluations. Based on a literature review, four dimensions, digital media use, sleep, eating habits, and activity, were determined. After preliminary item analysis, seven unqualified items were eliminated. A total of 1,152 college students and 8,082 middle school students were selected. Two independent sample t-tests, the Pearson correlations, and confirmatory factor analysis, were used to evaluate the reliability and validity of the questionnaire. The final questionnaire consisted of 4 dimensions covering 29 items, and the variance cumulative contribution was 62.65%. Cronbach's α for the total questionnaire was 0.950 and ranged from 0.817 to 0.904 for each dimension. The Pearson correlation coefficients between each item and the total score ranged from 0.360 to 0.755, and the Pearson correlation coefficient between each item and its dimension was between 0.575 and 0.841. Confirmatory factor analysis showed that the indices of CFI, TLI and RMSEA were 0.911, 0.901 and 0.043, respectively, which is a good degree of fit. The self-rating scale is consistent with the evaluation standard of psychometrics and can be used to evaluate the degree of biological rhythm disorder in adolescents.

2.
Br J Nutr ; : 1-20, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632975

RESUMO

To investigate the association between the Metabolic Score for Visceral Fat (METS-VF) and risk of type 2 diabetes mellitus (T2DM) and compare the predictive value of the METS-VF for T2DM incidence with other obesity indices in Chinese people. A total of 12,237 non-T2DM participants aged over 18 from the Rural Chinese Cohort Study of 2007-2008 were included at baseline and followed up during 2013-2014. The cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between baseline METS-VF and T2DM risk. Restricted cubic splines were used to model the association between METS-VF and T2DM risk. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the ability of METS-VF to predict T2DM incidence. During a median follow-up of 6.01 (5.09-6.06) years, 837 cases developed T2DM. After adjusting for potential confounding factors, the adjusted HR (95% CI) for the highest versus lowest METS-VF quartile was 5.97 (4.28-8.32), with a per 1-standard deviation increase in METS-VF positively associated with T2DM risk. Positive associations were also found in the sensitivity and subgroup analyses, respectively. A significant nonlinear dose-response association was observed between METS-VF and T2DM risk for all participants (Pnonlinearity = 0.0347). Finally, the AUC value of METS-VF for predicting T2DM was largest among six indices. The METS-VF may be a reliable and applicable predictor of T2DM incidence in Chinese people regardless of sex, age, or body mass index.

3.
Psychoneuroendocrinology ; 134: 105435, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34649104

RESUMO

OBJECTIVE: To evaluate whether gestational diabetes mellitus (GDM) is associated with increased risks of autistic traits and attention deficit/hyperactivity disorder (ADHD) among offspring and whether placental inflammatory and oxidative stress cytokines play an intermediary role. METHODS: Based on a prospective cohort study from China, namely, the Ma'anshan Birth Cohort study (MABC), 3260 mother-child pairs were included. Autistic traits and ADHD symptoms among children were assessed at 18 months and 36 months, respectively. The mRNA expression levels of fourteen placental cytokines were determined using PCR. Logistic regression analysis was used to examine the associations between GDM and the risks of autistic traits or ADHD symptoms. Mediation analysis was used to assess the potential mediation effects of certain placental inflammatory factors. RESULTS: Of the 3260 children, 419 (12.85%) were exposed to GDM. The prevalence rates of autistic traits and ADHD symptoms were 13.86% and 6.4%, respectively. A 48.6% increased risk of autistic traits was observed among offspring born to mothers with GDM [odds ratio (OR) = 1.49, 95% confidence interval (95%CI): 1.11-2.00)], while no significant association was found in terms of ADHD symptoms. There were significant positive associations between GDM and IL-10 expression and between HIF1-α and CRP mRNA expression and a significant negative association between GDM and CD206 mRNA expression. The expression of MCP-1 mRNA was negatively associated with the risk of autistic traits [adjusted OR = 0.73 (95%CI: 0.73-0.55)]. The levels of TNF-α were positively associated with the risk of ADHD symptoms [OR = 2.11 (95%CI: 1.39-3.21)], while GRP78 was inversely associated with it [OR = 0.64 (95%CI: 0.44-0.94)]. However, none of the 14 placental cytokines was involved as a key mediator. CONCLUSION: Our findings suggest that GDM may act as a risk factor for autistic traits in offspring, while the biological mechanisms may not involve the 14 placental cytokines studied. No significant association between GDM and ADHD symptoms was observed.

4.
J Hazard Mater ; 416: 125885, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492823

RESUMO

Iron-based materials have been widely used for treating uranium-containing wastewater. However, the iron-uranium solids originating by treating radioactive water through pollutant transfer methods has become a new uncontrolled source of persistent radioactive pollution. The safe disposal of such hazardous waste is not yet well-resolved. The electrochemical mineralization method was developed to rapidly purify uranium-containing wastewater through lattice doping in magnetite and recover uranium without generating any pollutants. An unexpected isolation of U3O8 from uranium-doped magnetite was discovered through in-situ XRD with a temperature variation from 300 °C to 700 °C. Through HRTEM and DFT calculation, it was confirmed that the destruction of the inverse spinel crystal structure during the gradual transformation of magnetite into γ-Fe2O3 and α-Fe2O3 promoted the migration, aggregation, and isolation of uranium atoms. Uniquely generated U3O8 and Fe2O3 were easily separated and over 80% uranium and 99.5% iron could be recovered. These results demonstrate a new strategy for uranium utilization and the environmentally friendly treatment of uranium-containing wastewater.


Assuntos
Urânio , Poluentes Radioativos da Água , Ferro , Estresse Oxidativo , Águas Residuárias , Poluentes Radioativos da Água/análise
5.
Nutrition ; 93: 111443, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34563934

RESUMO

OBJECTIVES: The aim of this study was to investigate the association of the Metabolic Score for Visceral Fat (METS-VF) with the risk for hypertension and to compare the ability of the METS-VF, the metabolic score for insulin resistance, visceral adiposity index, waist-to-height ratio, waist circumference, and body mass index to predict hypertension incidence based on a large prospective study of rural Chinese individuals. METHODS: In all, 10 297 non-hypertensive adults (≥18 y of age) from a rural Chinese cohort study in 2007 and 2008 were included at baseline and followed up in 2013 and 2014. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between baseline METS-VF and hypertension risk. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the ability of METS-VF to predict hypertension incidence. RESULTS: We identified 2071 hypertension cases during follow-up. After adjusting for multivariable confounding factors, the adjusted ORs (95% CIs) for the highest versus lowest METS-VF quartile overall and for men and women were 3.84 (3.23-4.56), 3.25 (2.48-4.24), and 4.14 (3.30-5.20), respectively. Also, per-SD increase in METS-VF was positively associated with hypertension risk overall and for men and women. Similar results were found in the sensitivity and subgroup analyses. Finally, the AUC value for hypertension was higher for METS-VF than the other five indices overall and for men and women. CONCLUSIONS: The present study indicated that METS-VF was positively associated with hypertension incidence and performed better in predicting hypertension risk than five other indices, which suggests that METS-VF is a reliable predictor of hypertension in the Chinese population.

6.
Ecotoxicol Environ Saf ; 225: 112736, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481356

RESUMO

BACKGROUND: Based on a medical record or questionnaire survey approach, previous epidemiological studies have investigated associations between maternal antibiotic exposure during pregnancy and childhood allergic diseases. However, biomonitoring studies on the prenatal low-dose antibiotic exposure, mainly from the environment and contaminated food, and in relation to children allergic diseases, are missing. OBJECTIVES: This research aimed to examine the associations between prenatal low-dose antibiotic exposure measured at multiple time points and children current allergic diseases at 4 years of age. METHODS: The current study including 2453 mother-child pairs was based on the Ma'anshan Birth Cohort study. Selected 41 antibiotics and their two metabolites, which including human antibiotics (HAs), preferred as human antibiotics (PHAs), veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs), in urine samples from 2453 pregnant women were biomonitored through liquid chromatography-triple quadrupole tandem mass spectrometry. Information on children current allergic diseases were collected via validated questionnaires. Generalized estimating equation were used to explore the associations between the repeated measurements of maternal urinary antibiotic over three trimesters and current allergic diseases in children. RESULTS: The detection rates of nine individual antibiotics in the three trimester during pregnancy are greater than 10%, and the 90th percentile concentration of the detected antibiotics ranges from 0.07 to 22.34 µg/g, and the 95th percentile concentration ranges from 0.17 to 59.57 µg/g. Among the participants, each one-unit concentration increment of sulfamethazine (adjusted OR=1.28, 95% CI: 1.10, 1.49, P-FDR=0.014) in the first trimester and ciprofloxacin (adjusted OR=1.17, 95% CI: 1.07, 1.28, P-FDR=0.008) in the second trimester were associated with an increased risk of current eczema in children. In the third trimester, each one-unit concentration increment of oxytetracycline (adjusted OR=1.90, 95% CI: 1.30, 2.78, P-FDR=0.014) was associated with an increased risk of current asthma in children. Gender-stratified analyses demonstrated that no gender differences were observed in the associations between prenatal antibiotic exposure and current allergic diseases in children. CONCLUSIONS: Maternal exposure to certain specific VAs or PVAs (sulfamethazine, ciprofloxacin and oxytetracycline) in different trimesters was associated with an increased risk of current asthma and current eczema in 4-year-old children. No gender differences were found in these associations. Further studies are warranted to confirm our findings and explore the potential mechanisms.


Assuntos
Antibacterianos , Exposição Materna , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Gravidez , Trimestres da Gravidez , Estudos Prospectivos
7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(8): 938-943, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34590560

RESUMO

OBJECTIVE: To investigate the risk factors and prognosis of early septic shock-related thrombocytopenia. METHODS: Retrospective analysis of clinical data of patients with septic shock admitted to the department of intensive care unit (ICU) of Northern Jiangsu People's Hospital from June 2016 to November 2020 was conducted. According to the lowest platelet count (PLT) in the early stage of septic shock (within 24 hours of using vasoactive drugs), the patients were divided into mild thrombocytopenia group [PLT (50-100)×109/L], severe thrombocytopenia group (PLT < 50×109/L) and normal platelet group (PLT > 100×109/L). The differences in general information, laboratory indicators, mechanical ventilation time, length of ICU stay, in-hospital stay, and 28-day mortality among the three groups were analyzed. Multivariate Logistic regression was used to analyze the influencing factors of thrombocytopenia, and the 28-day Kaplan-Meier survival curve of patients with different PLT levels was drawn. RESULTS: A total of 486 patients with septic shock were enrolled, including 123 patients with mild thrombocytopenia, 75 patients with severe thrombocytopenia and 288 patients with normal platelets. Patients with diabetes (χ2 = 30.460, P < 0.001), abdominal infection (χ2 = 15.024, P = 0.001), urinary tract infection (χ2 = 36.633, P < 0.001), bloodstream infection (χ2 = 7.755, P = 0.022), Gram negative (G-) bacilli infection (χ2 = 19.569, P < 0.001), hyperlactic acidemia (H = 23.404, P < 0.001), elevated procalcitonin (PCT, H = 43.368, P < 0.001), high acute physiology and chronic health evaluation II (APACHE II, F = 11.122, P < 0.001) and high sequential organ failure assessment (SOFA, F = 84.328, P < 0.001) were more likely to have thrombocytopenia within 24 hours of septic shock. Multivariate Logistic regression analysis of early septic shock-related thrombocytopenia showed that, diabetes [odds ratio (OR) = 0.19, 95% confidence interval (95%CI) was 0.08-0.42, P < 0.001], urinary tract infection (OR = 0.33, 95%CI was 0.13-0.83, P = 0.018), G- bacilli infection (OR = 0.20, 95%CI was 0.07-0.58, P = 0.003), hyperlactic acidemia (OR = 1.25, 95%CI was 1.07-1.46, P = 0.005) and high APACHE II score (OR = 0.85, 95%CI was 0.78-0.92, P < 0.001) were independent risk factors for platelets < 50×109/L. Abdominal infection was an independent risk factor for PLT (50-100)×109/L (OR = 0.56, 95%CI was 0.34-0.95, P = 0.03). High SOFA score was an independent risk factor for PLT ≤ 100×109/L [PLT < 50×109/L: OR = 2.03, 95%CI was 1.65-2.52, P < 0.001; PLT (50-100)×109/L: OR = 1.31, 95%CI was 1.16-1.48, P < 0.001]. There were no significant differences in mechanical ventilation time, length of ICU stay, and in-hospital stay among the three groups (H values were 0.142, 2.134, and 3.990, respectively, all P > 0.05). The 28-day mortality of septic shock patients increased with the severity of thrombocytopenia (χ2 = 40.406, P < 0.001), and the 28-day mortality of severe thrombocytopenia group and mild thrombocytopenia group was significantly higher than those of the normal platelet group [66.7% (50/75), 43.1% (53/123) vs. 27.8% (80/288), both P < 0.05]. Kaplan-Meier survival curve analysis showed that the 28-day survival rate gradually decreased with the decrease of PLT, and the 28-day survival rate was higher in the normal platelet group (Log-Rank test: χ2 = 80.667, P < 0.001). CONCLUSIONS: Diabetes, abdominal infection, urinary tract infection, G- bacilli infection, hyperlactic acidemia, high APACHE II score, and high SOFA score are independent risk factors for early septic shock-related thrombocytopenia. Early thrombocytopenia in patients with septic shock indicates a high risk of 28-day death.


Assuntos
Sepse , Choque Séptico , Trombocitopenia , Humanos , Unidades de Terapia Intensiva , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/complicações , Trombocitopenia/complicações
8.
Hematology ; 26(1): 724-733, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34555294

RESUMO

ABSTRACTBone marrow microenvironment provides critical regulatory signals for lineage differentiation and maintenance of HSC quiescence, and these signals also contribute to hematological myeloid malignancies. Macrophages exhibit high phenotypic heterogeneity under both physiological and pathological conditions and are mainly divided into proinflammatory M1 and anti-inflammatory M2 macrophages. Furthermore, osteoclasts are multinucleated giant cells that arise by fusion of monocyte/macrophage-like cells, which are commonly known as bone macrophages. Emerging evidence suggests that macrophages and osteoclasts originating from myeloid progenitors lead to two competing differentiation outcomes, and they appear to play an important role in the onset, progression, and bone metastasis of solid cancers. However, little is known about their role in the development of hematological malignancies. In this review, we focus on macrophages and osteoclasts, their role in leukemia, and the potential for targeting these cells in this disease.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34585354

RESUMO

The objective of this study is to investigate the mediating effect of placental inflammatory biomarkers on the relationship between prenatal phthalate coexposure and cognitive development in preschoolers. A subgroup of 1660 mother-child pairs from the Ma'anshan Birth Cohort study were included. We measured the levels of phthalate metabolites of dibutyl phthalate (DBP), butyl benzyl phthalate (BBzP), and di (2-ethylhexyl) phthalate (DEHP) in all the women included in the study from three urine samples collected in each of the trimesters. A potency-weighted sum of coexposure to DBP, BBzP, and DEHP (indicator: ∑PAE) was calculated. The mRNA of the proinflammatory cytokine IL-6 and the classically activated macrophage (M1) biomarker CD68 was analyzed using placental tissues. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition-Chinese was used to evaluate the full-scale intelligence quotient (FSIQ) of children aged 2.5-6 years. Average ∑PAEs and ∑PAEs in each trimester were associated with IL-6 and CD68. ∑PAE in the first trimester was positively associated with IL-6 (ß = 0.11, 95% CIs = 0.03-0.19) and CD68 (ß = 0.16, 95% CIs = 0.04-0.28), and negatively associated with FSIQ (ß =-0.06, 95% CIs = -0.11 to -0.02), verbal comprehension (ß =-0.06, 95% CIs = -0.11 to -0.01), and processing speed (ß =-0.07, 95% CIs = -0.12 to -0.01). Additionally, sex discrepancies were observed for the mediating effects of placental inflammation on the relationships between ∑PAE and children's cognitive development. For instance, the association between ∑PAE in early pregnancy and FSIQ was partially mediated by IL-6 (estimated proportion mediated: 21.85%) and CD68 (estimated proportion mediated: 16.2%). Gender-specific associations and trimester-specific relationships of prenatal multiple phthalate coexposure were revealed. ∑PAE in the first trimester of pregnancy was associated with increased of placental inflammation, and a decrease in preschoolers' cognitive development. In boys, placental IL-6 and CD68 elevation resulting from phthalates might be potential mechanisms of poor cognitive development.

10.
Arch Virol ; 166(11): 3189-3192, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34524537

RESUMO

Porcine circovirus type 2 (PCV2) is the etiological agent of post-weaning multisystemic wasting syndrome (PMWS). The original prevalent genotype, PCV2a, has been replaced by genotypes 2b and 2d in the swine population worldwide. The Rep protein is critical for viral replication. Comparison of a large number of Rep protein amino acid (aa) sequences showed that three sites distinguish genotype 2b from genotype 2d. In order to analyze the effect of exchanging the amino acids (asparagine and serine) at position 6 in the Rep proteins of PCV2b and PCV2d, two wild-type and two mutant viruses were rescued. Real-time quantitative PCR and a one-step growth curve were used to determine the viral load to assess the replication ability of the rescued viruses. The results showed that there was no significant difference in in vitro performance between the wild-type PCV2b and the mutated virus, while the mutation of PCV2d enhanced viral replication.

11.
Chem Commun (Camb) ; 57(80): 10411-10414, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34545862

RESUMO

Herein we report a [Cp*RhCl2]2-catalyzed coupling cyclization of two different classes of allenes with 2,3-allenoic acids affording 2(5H)-furanone skeletons of products and 2,3-allenols forming a conjugated (E)-enal or enone functionality to the ß-position of the 2(5H)-furanones. These products are important building blocks for the syntheses of potentially bioactive compounds. The reaction proceeded via the nucleometalation, insertion, and stereodefined 1,4-H delivery carried by rhodium.

12.
Oxid Med Cell Longev ; 2021: 7277966, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394833

RESUMO

Recent progress has been made in understanding the roles and mechanisms of endoplasmic reticulum (ER) stress in the development and pathogenesis of diabetic nephropathy (DN). Hyperglycemia induces ER stress and apoptosis in renal cells. The induction of ER stress can be cytoprotective or cytotoxic. Experimental treatment of animals with ER stress inhibitors alleviated renal damage. Considering these findings, the normalization of ER stress by pharmacological agents is a promising approach to prevent or arrest DN progression. The current article reviews the mechanisms, roles, and therapeutic aspects of these findings.

13.
Waste Manag ; 133: 19-27, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34343864

RESUMO

The aim of this study is to examine the effect of bamboo sphere on the organic matter decomposition and humification of food waste composting. Food waste composting were carried out on four treatments, namely control (CK), 3% (T1), 6% (T2) and 9% (T3) (w/w) bamboo sphere treatments. Results showed that adding bamboo sphere facilitated the organic matter decomposition and increased the seed germination index. The number of cells in T2 treatment was always the highest during the composting process. Furthermore, the final humic substances and humic acid contents increased by 41.08% and 68.3%, respectively, in 6% bamboo sphere treatment. Fourier transform infrared and excitation-emission matrix fluorescence spectroscopy analysis revealed that adding bamboo sphere accelerated the humification of composting with more aromatic structures and humic acid-like substances. GC-MS studies revealed that the compost products of 6% bamboo sphere treatment had more ring structures, and thus enhanced the humification.


Assuntos
Compostagem , Eliminação de Resíduos , Alimentos , Substâncias Húmicas/análise , Esterco , Solo
14.
Lung Cancer ; 160: 1-7, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34364112

RESUMO

OBJECTIVES: Primary pulmonary salivary gland-type tumors (PSGTs) mainly comprise of mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), which are rare and molecularly poorly understood. This study aimed to profile the molecular alterations of PSGTs via targeted next-generation sequencing (NGS). MATERIAL AND METHODS: Immunohistochemistry was used to screen PSGTs in 32 patients and MAML2 and MYB rearrangements were detected using fluorescence in situ hybridization. 1021-Genepanel of targeted NGS was conducted to profile genomic mutations in all the PSGT patients. RESULTS: Among the 32 patients, 25 had MEC and 7 had ACC. MAML2 and MYB rearrangements were detected in 80.0% (20/25) of the MEC and 71.4% (5/7) of the ACC patients. Among the MEC patients, 10 (40.0%) had ≥1 mutation, and 6 of them had 11 isolated mutations with abundance >5%, namely NFE2L2, MYOD1, INPP4B, CCND2, SNTG1, HSPD1, TGFBR1, RBM10, NOTCH4, ASXL1, and PTPRD mutations. The remaining 4 patients had 9 mutations with abundance <5%, namely KMT2A, PDCD11, FLT1, BRCA2, APC, SLX4, FOXP1, FGFR1, and HRAS mutations. All the ACC patients had mutations, which were enriched in 5 pathways including the PI3K and NOTCH pathways, chromatin and cytoskeleton remodeling, and DNA damage. These results explain PSGTs harbor distinct driver features of MAML2 or MYB rearrangement, accompanied with wide mutational diversity with very low rate of somatic mutation. Several important pathways, including the NOTCH and PI3K pathways, and chromatin remodeling could be targeted to improve the survival in patients with ACC.

15.
Diabetes Res Clin Pract ; 179: 108997, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34371063

RESUMO

AIMS: To evaluate the risk of type 2 diabetes mellitus (T2DM) in a prospective study with hypertriglyceridemic waist-to-height ratio (HWHtR) and its dynamic status. METHODS: We collected data for 12,248 participants ≥18 years in this study. Cox's proportional-hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM risk by baseline HWHtR. Multiple logistic regression analysis was used to estimate odds ratios (ORs) and 95% CIs for T2DM risk by transformation in HWHtR. RESULTS: We identified 839 T2DM cases during a median follow-up of 5.92 years. Compared with normal TG level and normal WHtR, T2DM risk was increased with high TG level and high WHtR (aHR 2.04, 95% CI 1.49-2.79). Similar results were observed in subgroup analyses by sex and age. During follow-up, T2DM risk was increased with stable high TG level and high WHtR (aOR 4.45, 95% CI 2.76-7.17) compared with stable normal TG level and normal WHtR. The results above were robust in sensitivity analyses. CONCLUSIONS: HWHtR phenotype and its dynamic status were associated with risk of T2DM. Our study suggests that primary prevention and avoiding the appearance of the HWHtR phenotype in the rural Chinese population may reduce the T2DM risk.

16.
Acta Pharmacol Sin ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341510

RESUMO

Dysregulation of NLRP3 inflammasome results in uncontrolled inflammation, which participates in various chronic diseases. TWIK2 potassium channel mediates potassium efflux that has been reported to be an essential upstream mechanism for ATP-induced NLRP3 inflammasome activation. Thus, TWIK2 potassium channel could be a potential drug target for NLRP3-related inflammatory diseases. In the present study we investigated the effects of known K2P channel modulators on TWIK2 channel expressed in a heterologous system. In order to increase plasma membrane expression and thus TWIK2 currents, a mutant channel with three mutations (TWIK2I289A/L290A/Y308A) in the C-terminus was expressed in COS-7 cells. TWIK2 currents were assessed using whole-cell voltage-clamp recording. Among 6 known K2P channel modulators tested (DCPIB, quinine, fluoxetine, ML365, ML335, and TKDC), ML365 was the most potent TWIK2 channel blocker with an IC50 value of 4.07 ± 1.5 µM. Furthermore, ML365 selectively inhibited TWIK2 without affecting TWIK1 or THIK1 channels. We showed that ML365 (1, 5 µM) concentration-dependently inhibited ATP-induced NLRP3 inflammasome activation in LPS-primed murine BMDMs, whereas it did not affect nigericin-induced NLRP3, or non-canonical, AIM2 and NLRC4 inflammasomes activation. Knockdown of TWIK2 significantly impaired the inhibitory effect of ML365 on ATP-induced NLRP3 inflammasome activation. Moreover, we demonstrated that pre-administration of ML365 (1, 10, 25 mg/kg, ip) dose-dependently ameliorated LPS-induced endotoxic shock in mice. In a preliminary pharmacokinetic study conducted in rats, ML365 showed good absolute oral bioavailability with F value of 22.49%. In conclusion, ML365 provides a structural reference for future design of selective TWIK2 channel inhibitors in treating related inflammatory diseases.

17.
Nanoscale Res Lett ; 16(1): 129, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34370102

RESUMO

Zinc oxide nanoparticles (ZnO NPs) are used in a wide range of applications including industry, commercial products and medicine field. Numerous mechanistic studies for ZnO NPs' toxicity were performed on pristine (fresh) NPs. However, the cytotoxicity induced by the transformed (aged) ZnO NPs and the underlying mechanisms remain unclear. Here, we observed the physicochemical transformation of ZnO NPs underwent over time, followed by evaluating the cytotoxicity of fresh and aged NPs. We found that fresh ZnO NPs induced higher apoptosis level than their aged counterparts. Accordingly, RNA sequencing data from aged ZnO NP-treated human-hamster hybrid (AL) cells showed that p53, PI3k-Akt, FoXO, Glutathione, ErbB, HIF-1, Oxytocin and Jak-STAT signaling pathways were enriched but no apoptosis pathway. Quantitative PCR results revealed the significantly higher mRNA level of IL1B and CD69 in fresh NP-treated groups compared to that of aged ZnO NP- and zinc chloride-treated groups. The above results indicated that the lower cytotoxicity of aged ZnO NPs is partially attributed to their reduced potency in inducing apoptosis. The transcriptional regulation of multiple signal pathways activated by aged NPs may help to build the cellular homeostasis. Taken together, our findings highlight the influence of aging (environmental transformation) process of ZnO NPs on their toxicities and biological consequences.

19.
Sci Total Environ ; 796: 148620, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34274662

RESUMO

AIMS: The association of long-term ambient air pollution and hypertension has been inconsistently reported. We performed an updated systematic review and meta-analysis to assess the association between long-term exposure to ambient air pollution and risk of hypertension in adults and in children. METHODS: PubMed, EMBASE, and Web of Science were searched up to August 7, 2020 for published articles examining the association of long-term exposure to ambient air pollution, including particulate matter (PM; ultrafine particles, PM1, PM1-2.5, PM2.5, PM2.5-10 and PM10), nitrogen dioxide (NO2), nitrogen oxides (NOx), sulfur dioxide (SO2), ozone (O3), carbon monoxide (CO) and hypertension. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for hypertension with each 10-µg/m3 increase in air pollutants were calculated by random-effects models. RESULTS: We included 57 studies (53 of adults and 4 of children) in the meta-analysis. Risk of hypertension was significantly increased in adults with each 10-µg/m3 increase in exposure to PM2.5 (OR 1.10, 95% CI 1.07-1.14; I2 = 93.1%; n = 37), PM10 (1.04, 1.02-1.07; I2 = 44.8%; n = 22), and SO2 (1.21, 1.08-1.36; I2 = 96.6%; n = 3). Hypertension was not significantly associated with PM1 (n = 2), PM2.5-10 (n = 16), NO2 (n = 27), or NOx (n = 17). In children, the summary ORs (95% CIs) for each 10-µg/m3 increase in PM2.5, PM10, SO2 and O3 were 2.82 (0.51-15.68; I2 = 83.8%; n = 2), 1.15 (1.01-1.32; I2 = 0; n = 2), 8.57 (0.13-575.58; I2 = 94.2%; n = 2), and 1.26 (0.81-1.09, I2 = 91.6%; n = 2), respectively. CONCLUSIONS: Long-term ambient air pollution is a potential risk factor for hypertension in adults. More studies are needed to explore the effects of long-term air pollution on hypertension in children.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Hipertensão , Ozônio , Adulto , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Ozônio/efeitos adversos , Ozônio/análise , Material Particulado/efeitos adversos , Material Particulado/análise
20.
Int J Biol Sci ; 17(10): 2606-2621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326697

RESUMO

Cisplatin (DDP) was reported to improve pathological complete response (pCR) rates in triple-negative breast cancer (TNBC) patients, however, the molecular mechanism still remains largely unknown. Emerging evidence suggested that some chemotherapeutic drugs played anti-tumor effects by inducing cell pyroptosis. Nevertheless, whether pyroptosis contributes to the DDP-induced anti-tumor effect in TNBC remains unexploited. In the present study, NLRP3/caspase-1/GSDMD pyroptosis pathway was involved in the DDP-induced anti-tumor effect of TNBC in vitro and in vivo, providing evidence that DDP might induce pyroptosis in TNBC. Moreover, DDP activated NLRP3/caspase-1/GSDMD pyroptosis pathway by up-regulating the long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3). Furthermore, knockdown of MEG3 not only partly abolished the activation effect of DDP on NLRP3/caspase-1/GSDMD pathway-mediated pyroptosis, but also reversed the suppression of DDP on tumor growth and metastasis ability in vitro and in vivo, further confirming that MEG3 may partially mediate the pyroptotic signaling upon DDP treatment. Thus, our data uncovered a novel mechanism that DDP induced pyroptosis via activation of MEG3/NLRP3/caspase-1/GSDMD pathway in TNBC to exert anti-tumor effects, which may help to develop new strategies for the therapeutic interventions in TNBC.

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