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1.
Cell ; 157(6): 1292-1308, 2014 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-24906148

RESUMO

Beige fat, which expresses the thermogenic protein UCP1, provides a defense against cold and obesity. Although a cold environment is the physiologic stimulus for inducing beige fat in mice and humans, the events that lead from the sensing of cold to the development of beige fat remain poorly understood. Here, we identify the efferent beige fat thermogenic circuit, consisting of eosinophils, type 2 cytokines interleukin (IL)-4/13, and alternatively activated macrophages. Genetic loss of eosinophils or IL-4/13 signaling impairs cold-induced biogenesis of beige fat. Mechanistically, macrophages recruited to cold-stressed subcutaneous white adipose tissue (scWAT) undergo alternative activation to induce tyrosine hydroxylase expression and catecholamine production, factors required for browning of scWAT. Conversely, administration of IL-4 to thermoneutral mice increases beige fat mass and thermogenic capacity to ameliorate pre-established obesity. Together, our findings have uncovered the efferent circuit controlling biogenesis of beige fat and provide support for its targeting to treat obesity.


Assuntos
Tecido Adiposo Marrom/metabolismo , Eosinófilos/metabolismo , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Macrófagos/metabolismo , Transdução de Sinais , Adipócitos Marrons/metabolismo , Animais , Catecolaminas/metabolismo , Temperatura Baixa , Interleucina-13/genética , Interleucina-4/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , Obesidade/metabolismo , Receptores CCR2/metabolismo , Fator de Transcrição STAT6/metabolismo , Termogênese
2.
EMBO Rep ; 25(3): 1055-1074, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38351372

RESUMO

Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. However, the molecular basis for HSC activation remains poorly understood. Herein, we demonstrate that primary cilia are present on quiescent HSCs but exhibit a significant loss upon HSC activation which correlates with decreased levels of the ciliary protein intraflagellar transport 88 (IFT88). Ift88-knockout mice are more susceptible to chronic carbon tetrachloride-induced liver fibrosis. Mechanistic studies show that the X-linked inhibitor of apoptosis (XIAP) functions as an E3 ubiquitin ligase for IFT88. Transforming growth factor-ß (TGF-ß), a profibrotic factor, enhances XIAP-mediated ubiquitination of IFT88, promoting its proteasomal degradation. Blocking XIAP-mediated IFT88 degradation ablates TGF-ß-induced HSC activation and liver fibrosis. These findings reveal a previously unrecognized role for ciliary homeostasis in regulating HSC activation and identify the XIAP-IFT88 axis as a potential therapeutic target for liver fibrosis.


Assuntos
Cílios , Cirrose Hepática , Animais , Camundongos , Cílios/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fator de Crescimento Transformador beta/metabolismo
3.
Plant J ; 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38879817

RESUMO

Citrus is a model plant for studying adventitious embryos, a form of asexual reproduction controlled by a single dominant gene, RWP. This gene has been identified as the causal gene for nucellar embryogenesis, but its function has not yet been fully understood. In this study, we used the fast-growing Fortunella hindsii as a system to explore chromatin accessibility during the nucellar embryony initiation, emphasizing elevated chromatin accessibility in polyembryonic (PO) genotypes compared to monoembryonic ones (MO). Notably, a higher level of accessible chromatin was observed in one allele of the promoter region of FhRWP, consistent with increased expression of the allele carrying the causal structural variant. By independently performing RNAi and gene editing experiments on PO genotypes, we found the downregulation of FhRWP expression could reduce the number of nucellar embryos, while its knockout resulted in abnormal axillary bud development. In overexpression experiments, FhRWP was identified as having the unique capability of inducing the embryogenic callus formation in MO stem segments, possibly through the regulation of the WUS-CLV signaling network and the ABA and cytokinin pathway, marking the inaugural demonstration of FhRWP's potential to reignite somatic cells' embryogenic fate. This study reveals the pleiotropic function of RWP in citrus and constructs a regulatory network during adventitious embryo formation, providing a new tool for bioengineering applications in plant regeneration.

4.
Eur J Neurosci ; 59(7): 1428-1440, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38151046

RESUMO

Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high-risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol-O-methyltransferase (COMT) genes, and paranoid and motor-impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor-impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor-impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high-risk psychotic symptoms in MAUD patients.


Assuntos
Metanfetamina , Polimorfismo de Nucleotídeo Único , Humanos , Catecol O-Metiltransferase/genética , Dopamina , Metanfetamina/efeitos adversos , Genótipo , Metilação
5.
Opt Lett ; 49(4): 1097-1100, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359262

RESUMO

We experimentally extend the nonlinear Gaussian to flat-top beam shaping from one to two dimensions through a three-dimensional nonlinear photonic crystal. Employing a near-infrared femtosecond laser, we induce a modification inside lithium niobate to achieve a second-order nonlinear optical coefficient modulation in three dimensions. The flat-topped truncation of wavefront has been adjusted in a mutual perpendicular coordinate separately. Among the generated flat-topped beams, the optimal flatness is 97.1%, and the nonlinear conversion efficiency is 10-2 at the peak power of 37 kW with the interaction length of 630 µm. By adding an extra dimension, our work simultaneously enables full-wavefront flat-top distribution and nonlinear frequency conversion.

6.
Acta Pharmacol Sin ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886550

RESUMO

Urolithin A (UroA), a dietary phytochemical, is produced by gut bacteria from fruits rich in natural polyphenols ellagitannins (ETs). The efficiency of ETs metabolism to UroA in humans depends on gut microbiota. UroA has shown a variety of pharmacological activities. In this study we investigated the effects of UroA on atherosclerotic lesion development and stability. Apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-cholesterol diet for 3 months to establish atherosclerosis model. Meanwhile the mice were administered UroA (50 mg·kg-1·d-1, i.g.). We showed that UroA administration significantly decreased diet-induced atherosclerotic lesions in brachiocephalic arteries, macrophage content in plaques, expression of endothelial adhesion molecules, intraplaque hemorrhage and size of necrotic core, while increased the expression of smooth muscle actin and the thickness of fibrous cap, implying features of plaque stabilization. The underlying mechanisms were elucidated using TNF-α-stimulated human endothelial cells. Pretreatment with UroA (10, 25, 50 µM) dose-dependently inhibited TNF-α-induced endothelial cell activation and monocyte adhesion. However, the anti-inflammatory effects of UroA in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) were independent of NF-κB p65 pathway. We conducted RNA-sequencing profiling analysis to identify the differential expression of genes (DEGs) associated with vascular function, inflammatory responses, cell adhesion and thrombosis in UroA-pretreated HUVECs. Human disease enrichment analysis revealed that the DEGs were significantly correlated with cardiovascular diseases. We demonstrated that UroA pretreatment mitigated endothelial inflammation by promoting NO production and decreasing YAP/TAZ protein expression and TEAD transcriptional activity in TNF-α-stimulated HUVECs. On the other hand, we found that UroA administration modulated the transcription and cleavage of lipogenic transcription factors SREBP1/2 in the liver to ameliorate cholesterol metabolism in ApoE-/- mice. This study provides an experimental basis for new dietary therapeutic option to prevent atherosclerosis.

7.
J Cell Physiol ; 238(11): 2600-2611, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37683035

RESUMO

The primary cilium is increasingly recognized as a crucial player in the physiology of biliary epithelial cells (BECs). However, the precise role of primary cilia in the development of age-related biliary fibrosis remains unclear. Herein, using cilium-deficient mice, we demonstrate that disruption of ciliary homeostasis in BECs in aged mice leads to significant bile duct proliferation, augmented biliary fibrosis, and heightened indicators of liver injury. Our RNA-sequencing data revealed a dysregulation in genes associated with various biological processes such as bile secretion, fatty acid metabolism, and inflammation. Loss of primary cilia also significantly enhanced signaling pathways driving the development of biliary fibrosis. Our findings collectively suggest that loss of primary cilia in the BECs of aged mice initiates a cascade of signaling events that contribute to biliary fibrosis, highlighting the primary cilium as a potential therapeutic target in the treatment of fibrosing cholangiopathies.


Assuntos
Cílios , Hepatopatias , Animais , Camundongos , Cílios/metabolismo , Hepatopatias/metabolismo , Células Epiteliais/metabolismo , Fibrose
8.
Anal Chem ; 95(5): 2741-2749, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36689633

RESUMO

Residues of organophosphorus pesticides (OPs) raise considerable concern, while identifying OPs from unknown sources is still a challenge to onsite fluorescence techniques. Herein, a dual-emission-capture sensor module, based on a TPB-DMTP@S-CDs/MnO2 fluorescence composite, is developed for OP fingerprint recognition. TPB-DMTP@S-CDs/MnO2, synthesized by a hydrothermal method and self-assembly, is spectrographically validated as a dual-wavelength fluorescence source. OP-sensitive catalysis (acetylcholinesterase on acetylthiocholine chloride) is designed to regulate fluorescence by decomposing quenchable MnO2. A flexibly fabricated sensor module supports the optimal dual-wavelength fluorescence excitations and captures and converts fluorescence emissions into equivalent photocurrents for feasible access. The most prominent finding is that dual-fluorescence emissions alternatively respond to levels, species, and multi-pH pretreatments of OPs due to varied MnO2 sizes and distributions. Therefore, OP fingerprint recognition is conducted by refining the multidimensional information from fluorescence-triggered photocurrents and preset hydrolyzation using principal component analysis and the rule of maximum covariance. The recommended method provides a wide dynamic range (1 × 10-6 ∼ 12 µg mL-1), a good limit of detection (7.9 × 10-7 µg mL-1), 15-day stability, and good selectivity to guarantee fingerprint recognition. For laboratory and natural samples, this method credibly identifies a single kind of OPs from multiple species at trace levels (10-5 µg mL-1) and performs well in two-component and multicomponent analyses.

9.
Mol Carcinog ; 62(8): 1228-1237, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37306026

RESUMO

Cervical cancer is a malignant tumor of the cervix in women. However, the pathogenesis of cervical cancer has not been fully understood. N6-methyladenosine (m6A) is a kind of RNA modification that plays a critical role in cancer development. We aim to find out the possible m6A regulatory mechanism of the fat mass and obesity-associated protein (FTO) on the development of cervical cancer. The proliferative capacity of cervical cancer cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), colony formation and 5-ethynyl-20-deoxyuridine (EdU) staining. The migration and invasion of cervical cancer cells were determined by transwell assay. The function of FTO on tumor growth was evaluated by a xenograft model. We found that FTO was highly expressed in cervical cancer tissues and cell lines. FTO silencing suppressed the proliferation, migration, and invasion of cervical cancer cells. Mechanistically, FTO modulated the m6A modification of Zinc finger E-box binding homeobox 1 (ZEB1) and Myelocytomatosis oncogene (Myc). Furthermore, ZEB1 and Myc overexpression reverse the effect of FTO knockdown on the malignant behaviors of cervical cancer cells. FTO may be a novel therapeutic target for cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Oncogenes , Linhagem Celular , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Linhagem Celular Tumoral , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética
10.
Pharmacogenomics J ; 23(4): 95-104, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36966195

RESUMO

Previous observational studies reported associations between non-steroidal anti-inflammatory drugs (NSAIDs) and major depressive disorder (MDD), however, these associations are often inconsistent and underlying biological mechanisms are still poorly understood. We conducted a two-sample Mendelian randomisation (MR) study to examine relationships between genetic variants and NSAID target gene expression or DNA methylation (DNAm) using publicly available expression, methylation quantitative trait loci (eQTL or mQTL) data and genetic variant-disease associations from genome-wide association studies (GWAS of MDD). We also assessed drug exposure using gene expression and DNAm levels of NSAID targets as proxies. Genetic variants were robustly adjusted for multiple comparisons related to gene expression, DNAm was used as MR instrumental variables and GWAS statistics of MDD as the outcome. A 1-standard deviation (SD) lower expression of NEU1 in blood was related to lower C-reactive protein (CRP) levels of -0.215 mg/L (95% confidence interval (CI): 0.128-0.426) and a decreased risk of MDD (odds ratio [OR] = 0.806; 95% CI: 0.735-0.885; p = 5.36 × 10-6). A concordant direction of association was also observed for NEU1 DNAm levels in blood and a risk of MDD (OR = 0.886; 95% CI: 0.836-0.939; p = 4.71 × 10-5). Further, the genetic variants associated with MDD were mediated by NEU1 expression via DNAm (ß = -0.519; 95% CI: -0.717 to -0.320256; p = 3.16 × 10-7). We did not observe causal relationships between inflammatory genetic marker estimations and MDD risk. Yet, we identified a concordant association of NEU1 messenger RNA and an adverse direction of association of higher NEU1 DNAm with MDD risk. These results warrant increased pharmacovigilance and further in vivo or in vitro studies to investigate NEU1 inhibitors or supplements for MDD.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla/métodos , Locos de Características Quantitativas/genética , Metilação de DNA/genética , Anti-Inflamatórios
11.
Biogerontology ; 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37792135

RESUMO

Sex is a crucial biological variable, and influence of biological sex on the change of gene expression in ageing skeletal muscle has not yet been fully revealed. In this study, the mRNA expression profiles were obtained from the Gene Expression Omnibus database. Key genes were identified by differential expression analysis and weighted gene co-expression network analysis. The gene set enrichment analysis software and Molecular Signatures Database were used for functional and enrichment analysis. A protein-protein interaction network was constructed using STRING and visualized in Cytoscape. The results were compared between female and male subgroups. Differentially expressed genes and enriched pathways in different sex subgroups shared only limited similarities. The pathways enriched in the female subgroup were more similar to the pathways enriched in the older groups without taking sex difference into consideration. The pathways enriched in the female subgroup were more similar to the pathways enriched in the older groups without taking sex difference into consideration. The muscle myosin filament pathways were downregulated in the both aged female and male samples whereas transforming growth factor beta pathway and extracellular matrix-related pathways were upregulated. With muscle ageing, the metabolism-related pathways, protein synthesis and degradation pathways, results of predicted immune cell infiltration, and gene cluster associated with slow-type myofibers drastically different between the female and male subgroups. This finding may indicate that changes in muscle type with ageing may differ between the sexes in vastus lateralis muscle.

12.
Environ Sci Technol ; 57(40): 15203-15212, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37729390

RESUMO

Cr(VI) rebound is the primary risk associated with the reduction remediation of Cr(VI)-contaminated soil. The potential impact of sulfites, which can be produced by microbial activities or originate from sulfur-containing remediation agents, on the Cr(VI) rebound in the vadose zone has been overlooked. When sulfites are present, the stability of CrxFe1-x(OH)3 is compromised and significantly inferior to that of Cr(OH)3, as demonstrated in this paper. First, Fe acts as a catalyst for the conversion of adsorbed sulfite to SO4·-, which subsequently triggers the oxidation of Cr(III) and results in the rebound of Cr(VI). The heterogeneous catalysis by Fe on the surface of CrxFe1-x(OH)3 plays a predominant role, contributing to 78% of the actual oxidation of Cr(III) among all employed catalytic processes. The presence of ambient Cl- can exacerbate the rebound effect of Cr(VI) by promoting the generation of HOCl. Furthermore, a portion of released Cr(VI) was reduced to Cr(III) by dissolved sulfite in the presence of dissolved Fe as a catalyst, thereby increasing the dissolution and migration risk associated with CrxFe1-x(OH)3. Hence, the presence of sulfites results in a significant increase in the Cr(VI) rebound and Cr(III) release from CrxFe1-x(OH)3. This challenges the conventional understanding of the stability of CrxFe1-x(OH)3.

13.
Environ Res ; 217: 114872, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36435499

RESUMO

Very few researches have concentrated on a variety of time scales to evaluate the association between temperature variation (TV) and childhood asthma (CA), and the evidence for the interaction of air pollutants on this association is lacking. In this study, we aim to estimate the relative risks (RRs) of CA due to TV by following metrics: diurnal temperature range (DTR), temperature changes between neighboring days (TCN), and temperature variability (TV0-t); to quantify the seasonal attributable fraction (AF) and number (AN) of CA due to TV; to examine the interactive effects of the TV and air pollutants on CA in different seasons. We mainly applied distributed lagged nonlinear model (DLNM) and conditional Poisson models to evaluate the associations between TV and outpatient visits for CA during 2014-2019 in Lanzhou, China. Additionally, the bivariate response surface model was used to examine the interplay effect of air pollutants. We found that in warm season, the risks of DTR maximum at lag5 (RR = 1.073, 95% CI: 1.017-1.133); TCN showed protective effect. In cold season, the risks of DTR peaked at lag8 (RR = 1.063, 95% CI: 1.027-1.100); the risks of TCN maximum at lag0 (RR = 1.058 95% CI: 1.009-1.109); the estimation of total cases maximized at TV0-4 in cold season (RR = 1.039 at TV0-3, 95% CI: 1.001, 1.077) and was the lowest at TV0-1 in warm season (RR = 0.999, 95% CI: 0.969, 1.030). In addition, the response surface model graphically pictured ambient air pollutants enhanced the DTR/TV0-4-CA effect for girls. In conclusion, the RRs of CA are markedly increased by TV exposure, particularly during the colder months. A combined evaluation of DTR, TCN, TV0-5∼TV0-6, NO2, SO2, and PM2.5 should be used to identify the adverse effects of TV on CA.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Feminino , Humanos , Criança , Poluentes Atmosféricos/análise , Temperatura , Estações do Ano , Temperatura Baixa , Asma/epidemiologia , Asma/etiologia , China/epidemiologia , Poluição do Ar/análise
14.
Ecotoxicol Environ Saf ; 256: 114836, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37001192

RESUMO

Previous studies on the association of endocrine-disrupting chemicals (EDCs) with metabolic dysfunction-associated fatty liver disease (MAFLD) are very limited. This study analyzed the association of EDCs exposure with MAFLD among 5073 American adults from the 2017-2018 National Health and Nutrition Examination Survey. The results showed that increased exposure to 3 EDCs metabolites (namely As, DiNP and PFOA) were significantly associated with MAFLD, the odds ratio of which were 1.819 (95% CI: 1.224, 2.702), 1.959 (95% CI: 1.224, 3.136) and 2.148 (95% CI: 1.036, 4.456), respectively. Further, the bayesian kernel machine regression model also revealed that phthalates exposure was strongly connected with the MAFLD, particularly in females and the elderly over 65. Moderating effect analysis suggested that higher body mass index (BMI) and inflammatory diet habit (indicated by dietary inflammatory index) strengthened the association between EDCs and MAFLD, whereas population with higher level of insulin sensitivity showed lower risk. In conclusion, our results suggest that either single or combined exposure to EDCs metabolites is link to MAFLD. Our findings also encourage people to sustain a healthy diet, normal levels of insulin sensitivity and BMI, which may help to alleviate the association of MAFLD risk in exposure to EDCs. These results also help us to better understand the association of EDCs and MAFLD and provide effective evidences for preventing MAFLD from the EDCs exposure aspect.


Assuntos
Disruptores Endócrinos , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Adulto , Idoso , Feminino , Humanos , Inquéritos Nutricionais , Teorema de Bayes , Índice de Massa Corporal
15.
J Craniofac Surg ; 34(4): e385-e387, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37157121

RESUMO

Giant congenital hemangiomas are rare, especially when combined with multiple complications. This article presents a case of a giant congenital hemangioma of the maxillofacial region in a neonate with combined thrombocytopenia, coagulation dysfunction, and heart failure, which was eventually treated surgically after a multidisciplinary consultation and achieved a good outcome.


Assuntos
Hemangioma Cavernoso , Hemangioma , Recém-Nascido , Humanos , Hemangioma/complicações , Hemangioma/diagnóstico por imagem , Hemangioma/cirurgia , Hemangioma Cavernoso/complicações
16.
J Therm Biol ; 112: 103422, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36796884

RESUMO

This study explored the facial skin temperature and thermal sensation of sub-tropically acclimated subjects in summer. We conducted a summer experiment that simulated the common indoor temperatures in Changsha, China. Twenty healthy subjects experienced five exposure conditions: 24, 26, 28, 30 and 32 °C with a relative humidity of 60%. During exposure (140min), the sitting participants documented their thermal sensation, comfort and acceptability of the environment. Their facial skin temperatures were continuously and automatically recorded by using iButtons. These facial parts include the forehead, nose, left and right ears, left and right cheeks and chin. The results found that the maximum facial skin temperature difference increased with air temperature reduction. The forehead skin temperature was the highest. Nose skin temperature is lowest when air temperature is not higher than 26 °C during summer. Correlation analysis confirmed that the nose is the potential facial part that is most suitable to evaluate thermal sensation. Based on the published winter experiment, we further explored their seasonal effects. The seasonal analysis showed that, compared with winter, thermal sensation is more sensitive to indoor temperature changes and facial skin temperatures were less susceptible to thermal sensation changes in summer. Facial skin temperatures were higher in summer under the same thermal conditions. It suggests that seasonal effects should be considered when facial skin temperature can be used as an important parameter for indoor environment control in the future through monitoring thermal sensation.


Assuntos
População do Leste Asiático , Temperatura Cutânea , Humanos , Estações do Ano , Sensação Térmica , Face
17.
Prostate ; 82(1): 13-25, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570375

RESUMO

INTRODUCTION: Androgen deprivation therapy (ADT) is a key treatment modality in the management of prostate cancer (PCa), especially for patients with metastatic disease. Increasing evidences suggest that patients who received ADT have increased incidence of diabetes, myocardial infarction, stroke, and even mortality. It is important to understand the pathophysiological mechanisms on how ADT increases cardiovascular risk and induces cardiovascular events, which would provide important information for potential implementation of preventive measures. METHODS: Twenty-six 12-week-old male SD rats were divided into four groups for different types of ADTs including: the bilateral orchidectomy group (Orx), LHRH agonist group (leuprolide), LHRH antagonist group (degarelix), and control group. After treated with drug or adjuvant injection every 3 weeks for 24 weeks, all rats were sacrificed and total blood were collected. Aorta, renal arteries, and kidney were preserved for functional assay, immunohistochemistry, western blot, and quantitative reverse-transcription polymerase chain reaction. RESULTS: In vascular reactivity assays, aorta, intrarenal, and coronary arteries of all three ADT groups showed endothelial dysfunction. AT1R and related molecules at protein and messenger RNA (mRNA) level were tested, and AT1R pathway was shown to be activated and played a role in endothelial dysfunction. Both ACE and AT1R mRNA levels were doubled in the aorta in the leuprolide group while Orx and degarelix groups showed upregulation of AT1R in the kidney tissues. By immunohistochemistry, our result showed higher expression of AT1R in the intrarenal arteries of leuprolide and degarelix groups. The role of reactive oxygen species in endothelial dysfunction was confirmed by DHE fluorescence, nitrotyrosine overexpression, and upregulation of NOX2 in the different ADT treatment groups. CONCLUSION: ADT causes endothelial dysfunction in male rats. GnRH receptor agonist compared to GnRH receptor antagonist, showed more impairment of endothelial function in the aorta and intrarenal arteries. Such change might be associated with upregulation and activation of AngII-AT1R-NOX2 induced oxidative stress in the vasculature. These results help to explain the different cardiovascular risks and outcomes related to different modalities of ADT treatment.


Assuntos
Antagonistas de Androgênios , Artérias , Endotélio Vascular , Leuprolida , Oligopeptídeos , Orquiectomia/métodos , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/análise , Antagonistas de Androgênios/metabolismo , Animais , Artérias/efeitos dos fármacos , Artérias/metabolismo , Artérias/patologia , Correlação de Dados , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Fatores de Risco de Doenças Cardíacas , Imuno-Histoquímica , Leuprolida/administração & dosagem , Leuprolida/efeitos adversos , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Ratos , Espécies Reativas de Oxigênio/análise , Receptor Tipo 1 de Angiotensina/análise , Receptor Tipo 1 de Angiotensina/metabolismo
18.
Indoor Air ; 32(10): e13138, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36305071

RESUMO

Facial skin temperature has been applied to evaluate thermal comfort in a few studies, but the related theoretical basis is not sufficient. We conducted a climate-controlled experiment in winter. The air temperatures were 12, 15, 18, 21, and 24°C, and the relative humidity was set to 60%. During exposure (140 min), the subjects were in a sedentary state, and their thermal sensation, comfort, and acceptability of perceived thermal environments were documented many times. iButton instruments were used to continuously and automatically record skin temperatures on the forehead, nose, right ear, right cheek, left cheek, left ear, and chin. The measurement accuracy of the corrected skin temperature was within 0.1°C after calibrating each i-Button. The experimental results showed that the skin temperatures at different measurement points varied significantly. The forehead skin temperature was the highest, whereas the nose, being the facial part, exhibited the lowest skin temperature (except 24°C). The uneven degree of the skin temperature distribution increased as air temperature decreased. Correlation analysis confirmed that the facial skin temperature can be used to evaluate thermal sensation. Nose skin temperature and the average skin temperature of the forehead, nose, and chin are the most suitable indicators of thermal sensation. The correlation between facial skin temperature and the thermal sensation was significantly higher after 15 min of exposure time than that during 0-15 min. This study provides a theoretical basis for using facial skin temperature to dynamically monitor thermal sensations.


Assuntos
Poluição do Ar em Ambientes Fechados , Temperatura Cutânea , Humanos , Temperatura , Sensação Térmica , Face
19.
Indoor Air ; 32(10): e13120, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36305076

RESUMO

This study aimed to explore the spatial and temporal trends of lung cancer burden attributable to residential radon exposure at the global, regional, and national levels. Based on the Global Burden of Disease Study (GBD) 2019, we collected the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life rate (ASDR) of lung cancer attributable to residential radon exposure from 1990 to 2019. The Joinpoint model was used to calculate the annual average percentage change (AAPC) to evaluate the trend of ASMR and ASDR from 1990 to 2019. The locally weighted regression (LOESS) was used to estimate the relationship of the socio-demographic index (SDI) with ASMR and ASDR. In 2019, the global ASMR and ASDR for lung cancer attributable to residential radon exposure were 1.03 (95% CI: 0.20, 2.00) and 22.66 (95% CI: 4.49, 43.94) per 100 000 population, which were 15.6% and 23.0% lower than in 1990, respectively. According to the estimation, we found the lung cancer burden attributable to residential radon exposure declined significantly in high and high-middle SDI regions, but substantially increased in middle and low-middle SDI regions from 1990 to 2019. Across age and sex, the highest burden of lung cancer attributable to residential radon exposure was found in males and elderly groups. In conclusion, the global burden of lung cancer attributable to residential radon exposure showed a declining trend from 1990 to 2019, but a relatively large increase was found in the middle SDI regions. In 2019, the burden of lung cancer attributable to residential radon exposure remained high, particularly in males, the elderly, and high-middle SDI regions compared with other groups.


Assuntos
Poluição do Ar em Ambientes Fechados , Neoplasias Pulmonares , Radônio , Masculino , Humanos , Idoso , Poluição do Ar em Ambientes Fechados/efeitos adversos , Carga Global da Doença , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Radônio/efeitos adversos
20.
Int J Mol Sci ; 23(22)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36430186

RESUMO

Tert-butylperoxy-2-ethylhexanoate (TBPEH) and tert-butyl peroxybenzoate (TBPB) promote the radical acylation of allyl ester with benzaldehyde to synthesize new carbonyl-containing compounds under solvent-free and metal-free conditions. This reaction is compatible with electron-donating and halogen groups and has excellent atom utilization and chemical selectivity. Furthermore, the synthetic compounds can further apply to the preparation of lactone, piperidine, tetrazole and oxazole.


Assuntos
Benzaldeídos , Ésteres , Ésteres/química , Peróxidos
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