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1.
Cell Death Dis ; 12(5): 436, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33934111

RESUMO

Atherosclerotic plaque vulnerability and rupture increase the risk of acute coronary syndromes. Advanced lesion macrophage apoptosis plays important role in the rupture of atherosclerotic plaque, and endoplasmic reticulum stress (ERS) has been proved to be a key mechanism of macrophage apoptosis. Intermedin (IMD) is a regulator of ERS. Here, we investigated whether IMD enhances atherosclerotic plaque stability by inhibiting ERS-CHOP-mediated apoptosis and subsequent inflammasome in macrophages. We studied the effects of IMD on features of plaque vulnerability in hyperlipemia apolipoprotein E-deficient (ApoE-/-) mice. Six-week IMD1-53 infusion significantly reduced atherosclerotic lesion size. Of note, IMD1-53 lowered lesion macrophage content and necrotic core size and increased fibrous cap thickness and vascular smooth muscle cells (VSMCs) content thus reducing overall plaque vulnerability. Immunohistochemical analysis indicated that IMD1-53 administration prevented ERS activation in aortic lesions of ApoE-/- mice, which was further confirmed in oxidized low-density lipoproteins (ox-LDL) induced macrophages. Similar to IMD, taurine (Tau), a non-selective ERS inhibitor significantly reduced atherosclerotic lesion size and plaque vulnerability. Moreover, C/EBP-homologous protein (CHOP), a pro-apoptosis transcription factor involved in ERS, was significantly increased in advanced lesion macrophages, and deficiency of CHOP stabilized atherosclerotic plaques in AopE-/- mice. IMD1-53 decreased CHOP level and apoptosis in vivo and in macrophages treated with ox-LDL. In addition, IMD1-53 infusion ameliorated NLRP3 inflammasome and subsequent proinflammatory cytokines in vivo and in vitro. IMD may attenuate the progression of atherosclerotic lesions and plaque vulnerability by inhibiting ERS-CHOP-mediated macrophage apoptosis, and subsequent NLRP3 triggered inflammation. The inhibitory effect of IMD on ERS-induced macrophages apoptosis was probably mediated by blocking CHOP activation.

2.
Talanta ; 230: 122328, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33934785

RESUMO

Scutellaria baicalensis is one of the widely used Chinese traditional medicines, and wogonin is one of major active components in it. However, the mechanism of action of wogonin has largely remained unclear. In this work, we designed a fluorescent probe, namely ATTO565-WGN, by conjugating wogonin with the fluorophore ATTO565 based on Mannich reaction via a flexible chain linker. In vitro assays verified that the ATTO565-WGN conjugate has a similar anti-proliferative activity to wogonin against human A549 and HeLa cancer cell lines. Combining co-localization and competition studies, confocal fluorescence imaging clearly demonstrated that the fluorescent wogonin probe predominantly located in mitochondrial area of living cells, indicating that wogonin acts at mitochondrion to exert its pharmacological functions. Significantly, the conjugated ATTO565 fluorophore conferred the wogonin probe STED (Stimulated Emission Depletion) feature, enabling STED fluorescence living cell imaging with a 55 nm of ultrahigh spatial resolution. This will greatly beneficial for the in situ investigation of interactions between wogonin and biological targets at the finely organized and dynamic mitochondria of living cells. Moreover, this work also provides novel insights into rational design of mitochondrion targeting fluorescence probes for ultrahigh resolution living cell imaging.

4.
Mycopathologia ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33847867

RESUMO

A severe outbreak of highly virulent and multi-resistant dermatophytosis by species in the Trichophyton mentagrophytes/T. interdigitale complex is ongoing in India. The correct identity of the etiologic agent is a much-debated issue. In order to define species limits, a taxonomic study was undertaken combining molecular, morphological, and physiological characteristics as evidence of classification. Molecular characteristics show that T. mentagrophytes s. str. and T. interdigitale s. str. can be distinguished with difficulty from each other, but are unambiguously different from the Indian genotype, T. indotineae by sequences of the HMG gene. The entities were confirmed by multilocus analysis using tanglegrams. Phenotypic characters of morphology and physiology are not diagnostic, but statistically significant differences are observed between the molecular siblings. These properties may be drivers of separate evolutionary trends. Trichophyton mentagrophytes represents the ancestral, homothallic cloud of genotypes with a probable geophilic lifestyle, while T. indotineae and T. interdigitale behave as anthropophilic, clonal offshoots. The origin of T. indotineae, which currently causes a significant public health problem, is zoonotic, and its emergence is likely due to widespread misuse of antifungals.

5.
J Formos Med Assoc ; 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33849750

RESUMO

BACKGROUND/PURPOSE: Atopic dermatitis (AD) is a common skin disease. At present, there is little evidence regarding its impact on patients' health-related quality of life (HRQoL) in Taiwan. Therefore, this study investigated the relationship between AD severity and patients' HRQoL in Taiwan. METHODS: Patients with AD were recruited from three hospitals in Taiwan from April 2018 to April 2019. AD severity was measured using the Scoring of AD (SCORAD) scale, and HRQoL was assessed using the Dermatology Life Quality Index (DLQI) and the five-level version of EuroQol five-dimension questionnaire (EQ-5D-5L). RESULTS: A total of 200 patients (mean age: 34.4 years) were recruited, including 103 males and 97 females. They were further classified as 79 mild, 72 moderate, and 58 severe AD patients according to their SCORAD scores. There was a positive correlation between their SCORAD and DLQI scores (Spearman's r = 0.77, p < 0.001). Patients with severe AD had higher scores in all the DLQI questions, particularly the symptoms, feelings, and work/school. In addition, both the EQ-5D visual analogue scale (VAS) scores and utility index values were negatively correlated with the SCORAD scores (Spearman's r = -0.46 and -0.60, respectively, both p < 0.001). Patients with higher AD severity had more problems with mobility, usual activity, pain/discomfort, and anxiety/depression, while demographic characteristics did not significantly affect HRQoL. CONCLUSION: Higher AD severity is associated with poorer HRQoL in Taiwanese AD patients, with AD's effects on symptoms, feelings, and work/school being the most troublesome. Meanwhile, demographic factors did not affect HRQoL significantly.

6.
J Hematol Oncol ; 14(1): 54, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794982

RESUMO

N6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic RNAs while accumulating studies suggest that m6A aberrant expression plays an important role in cancer. HNRNPA2B1 is a m6A reader which binds to nascent RNA and thus affects a perplexing array of RNA metabolism exquisitely. Despite unveiled facets that HNRNPA2B1 is deregulated in several tumors and facilitates tumor growth, a clear role of HNRNPA2B1 in multiple myeloma (MM) remains elusive. Herein, we analyzed the function and the regulatory mechanism of HNRNPA2B1 in MM. We found that HNRNPA2B1 was elevated in MM patients and negatively correlated with favorable prognosis. The depletion of HNRNPA2B1 in MM cells inhibited cell proliferation and induced apoptosis. On the contrary, the overexpression of HNRNPA2B1 promoted cell proliferation in vitro and in vivo. Mechanistic studies revealed that HNRNPA2B1 recognized the m6A sites of ILF3 and enhanced the stability of ILF3 mRNA transcripts, while AKT3 downregulation by siRNA abrogated the cellular proliferation induced by HNRNPA2B1 overexpression. Additionally, the expression of HNRNPA2B1, ILF3 and AKT3 was positively associated with each other in MM tissues tested by immunohistochemistry. In summary, our study highlights that HNRNPA2B1 potentially acts as a therapeutic target of MM through regulating AKT3 expression mediated by ILF3-dependent pattern.

7.
Environ Pollut ; 283: 117087, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33894629

RESUMO

With the rapid development of science and technology, 5G technology will be widely used, and biosafety concerns about the effects of 5G radiofrequency radiation on health have been raised. Drosophila melanogaster was selected as the model organism for our study, in which a 3.5 GHz radiofrequency radiation (RF-EMR) environment was simulated at intensities of 0.1 W/m2, 1 W/m2, and 10 W/m2. The activity of parent male and offspring (F1) male flies was measured using a Drosophila activity monitoring system under short-term and long-term 3.5 GHz RF-EMR exposure. Core genes associated with heat stress, the circadian clock and neurotransmitters were detected by QRT-PCR technology, and the contents of GABA and glutamate were detected by UPLC-MS. The results show that short-term RF-EMR exposure increased the activity level and reduced the sleep duration while long-term RF-EMR exposure reduced the activity level and increased the sleep duration of F1 male flies. Under long-term RF-EMR, the expression of heat stress response-related hsp22, hsp26 and hsp70 genes was increased, the expression of circadian clock-related per, cyc, clk, cry, and tim genes was altered, the content of GABA and glutamate was reduced, and the expression levels of synthesis, transport and receptor genes were altered. In conclusion, long-term RF-EMR exposure enhances the heat stress response of offspring flies and then affects the expression of circadian clock and neurotransmitter genes, which leads to decreased activity, prolonged sleep duration, and improved sleep quality.

8.
Sci Total Environ ; 772: 144568, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33770895

RESUMO

BACKGROUND: Temperature stress was reported to impact the gut-brain axis including intestinal microbiome and neuroinflammation, but the molecular markers involved remain unclear. We aimed to examine the effects of different temperature stress on the intestinal microbiome and central nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes. MATERIALS AND METHODS: Mice models were established under low temperature (LT), room temperature (RT), high temperature (HT), and temperature variation (TV) respectively for seven days. We examined temperature-induced changes of intestinal microbiome composition and the levels of its metabolites short-chain fatty acids (SCFAs), as well as the expressions of central NLRP3 inflammasomes and inflammatory cytokines. Redundancy analysis and Spearman correlation analysis were performed to explore the relationships between microbiome and NLRP3 inflammasomes and other indicators. RESULTS: HT and LT significantly increased the Alpha diversity of intestinal microbiome. Compared with RT group, Bacteroidetes were most abundant in LT group while Actinobacteria were most abundant in HT and TV groups. Nineteen discriminative bacteria were identified among four groups. LT increased the expressions of acetate and propionate while decreased that of NLRP3 inflammasomes; HT decreased the expression of butyrate while increased that of NLRP3 inflammasomes, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α; TV decreased the expression of propionate while increased that of NLRP3 inflammasomes and TNF-α. Microbiome distribution could significantly explain the differences in NLRP3 between comparison groups (LT&RT: R2 = 0.82, HT&RT: R2 = 0.86, TV&RT: R2 = 0.94; P < 0.05). The discriminative bacteria were significantly correlated with SCFAs but were correlated with NLRP3 inflammasomes and cytokines in the opposite direction. CONCLUSIONS: LT inhibits while HT and TV promote the activation of NLRP3 inflammasomes in brain, and intestinal microbiome and its metabolites may be the potential mediators. Findings may shed some light on the impact of temperature stress on gut-brain axis.


Assuntos
Microbioma Gastrointestinal , Inflamassomos , Animais , Encéfalo/metabolismo , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Temperatura
9.
Commun Biol ; 4(1): 364, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742082

RESUMO

The fruit fly, Drosophila melanogaster, has been used as a model organism for the molecular and genetic dissection of sleeping behaviors. However, most previous studies were based on qualitative or semi-quantitative characterizations. Here we quantified sleep in flies. We set up an assay to continuously track the activity of flies using infrared camera, which monitored the movement of tens of flies simultaneously with high spatial and temporal resolution. We obtained accurate statistics regarding the rest and sleep patterns of single flies. Analysis of our data has revealed a general pattern of rest and sleep: the rest statistics obeyed a power law distribution and the sleep statistics obeyed an exponential distribution. Thus, a resting fly would start to move again with a probability that decreased with the time it has rested, whereas a sleeping fly would wake up with a probability independent of how long it had slept. Resting transits to sleeping at time scales of minutes. Our method allows quantitative investigations of resting and sleeping behaviors and our results provide insights for mechanisms of falling into and waking up from sleep.

10.
Environ Res ; 197: 110985, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33744269

RESUMO

BACKGROUND: Considering the serious health burden caused by adverse weather events, increasing researches focused on the relationship between temperature variability (TV) and cause-specific mortality, but its association with cancer was not well explored. We aimed to investigate the impacts of TV on cancer mortality and examine the modifying effects of weather type and geographical location as well as other characteristics. MATERIALS AND METHODS: Daily city-specific data of cancer deaths, mean temperature (Tmean), maximum and minimum temperatures (Tmax and Tmin), relative humidity (RH), rainfall, and air pollutants were collected during 2016-2017 in 13 cities in Jiangsu Province, China. TV0-t was defined as the standard deviation of the daily Tmax and Tmin on the exposure 0-t days. A two-stage analysis was applied. First, a time-stratified case-crossover design was used to examine the odds ratio (OR) and attributable fraction of cancer mortality per 1 °C increase in TV by adjusting for potential confounders. Random effect meta-analysis was used to summarize the pooled ORs. Second, stratified analysis was performed for weather type, geographical location, demographics, and other city-level characteristics. The weather was defined as four types according to days during warm or cold season combined with high or low RH. RESULTS: A total of 303670 cases were included in our study. Meta-analysis showed that the ORs of cancer mortality per 1 °C increase in TV0-t significantly increased and peaked in TV0-2 (OR=1.0098, 95% CI: 1.0039-1.0157). The attributable fraction of TV0-2 on cancer mortality was 4.74%, accounting for 14395 deaths in the study period. Significant ORs of TV-related cancer mortality were found during the warm season combined with high RH and in the northern region of Jiangsu. Susceptible groups of TV-related cancer mortality were identified as female patients, patients aged 45-65 years, and those living in cities with lower per capita green area. CONCLUSIONS: TV can significantly increase the risk of cancer mortality, especially during warm and humid days and in the northern region of Jiangsu. Findings are of great significance to formulate urban planning, resource allocation, and health intervention to prolong the life of cancer patients.

11.
J Int Med Res ; 49(3): 300060521997588, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33682505

RESUMO

OBJECTIVES: To characterize differences in cardiac structure and function in hemodialysis (HD) patients with diabetic nephropathy (DN) and in those without using echocardiography and to determine their impact on the prediction of mortality using echocardiographic parameters. METHODS: Clinical, laboratory, and echocardiographic data were collected from patients commencing HD. RESULTS: Compared with those without DN, patients with DN had lower peak velocity of the early diastolic wave (e'), larger left atria, and higher peak early diastolic velocity (E)/e' and peak velocity of tricuspid regurgitation (TR). In addition, a larger proportion of DN patients had a combination of left ventricular (LV) diastolic dysfunction, cardiac valve calcification, moderate-to-severe cardiac valve regurgitation (CVR), and at least moderate pericardial effusion (PE). After accounting for age, sex, smoking, hypertension, hemoglobin, and albumin, DN was responsible for e' < 10 cm/s, E/e' >13 m/s, TR >2.8 m/s, LV diastolic dysfunction, CVR, and PE. LV diastolic dysfunction and E/e' >13 were the most useful predictors of mortality in patients with DN. CONCLUSIONS: Patients with DN who undergo HD tend to have worse LV diastolic function and are more likely to have heart valve problems. LV diastolic dysfunction and E/e' are predictors of death in DN patients.

12.
Sci Total Environ ; 778: 146325, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33725612

RESUMO

Sulfur could be introduced into paddy soils via dry or wet deposition, irrigation, and fertilization, which subsequently impacts the production of methylmercury (MeHg), a bioaccumulative neurotoxicant. However, effects of sulfur input on MeHg production are variable, possibly due to the multiple effects of sulfur on Hg mobility and/or microbial Hg methylators, leading to uncertainties in predicting MeHg risk. To address that, we explored the effects of different types and amounts of sulfur as well as concentrations of ambient sulfate on Hg methylation in paddy soils, and elucidated the mechanisms by quantifying changes in (1) Hg mobility and (2) microbial Hg methylators (e.g., sulfate-reducing bacteria, SRB). Our results indicated that MeHg levels increased by 40-86% and 30-96% in soils under various types (i.e., 200 mg kg-1 elemental sulfur, ammonium sulfate, sulfur-coated urea and potassium sulfate (K2SO4)) and different amounts (i.e., 100, 200 and 400 mg kg-1 K2SO4) of sulfur input. The enhanced MeHg production could be explained by increased Hg mobility but not changes in microbial Hg methylators. Besides, sulfate input increased MeHg levels (89-240%) in soils with low ambient sulfate levels (<100 mg kg-1) but had no effect on high-sulfate soils (>380 mg kg-1). These could be explained by the diverse responses of Hg mobility and microbial Hg methylators to sulfate input at different ambient sulfate levels. Our study opens the "black box" of Hg methylation under sulfur input, which would help reduce uncertainties in predicting MeHg risk in soils.

13.
Adv Mater ; 33(13): e2007605, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33599041

RESUMO

Skin-attachable gas sensors provide a next-generation wearable platform for real-time protection of human health by monitoring environmental and physiological chemicals. However, the creation of skin-like wearable gas sensors, possessing high sensitivity, selectivity, stability, and scalability (4S) simultaneously, has been a big challenge. Here, an ionotronic gas-sensing sticker (IGS) is demonstrated, implemented with free-standing polymer electrolyte (ionic thermoplastic polyurethane, i-TPU) as a sensing channel and inkjet-printed stretchable carbon nanotube electrodes, which enables the IGS to exhibit high sensitivity, selectivity, stability (against mechanical stress, humidity, and temperature), and scalable fabrication, simultaneously. The IGS demonstrates reliable sensing capability against nitrogen dioxide molecules under not only harsh mechanical stress (cyclic bending with the radius of curvature of 1 mm and cyclic straining at 50%), but also environmental conditions (thermal aging from -45 to 125 °C for 1000 cycles and humidity aging for 24 h at 85% relative humidity). Further, through systematic experiments and theoretical calculations, a π-hole receptor mechanism is proposed, which can effectively elucidate the origin of the high sensitivity (up to parts per billion level) and selectivity of the ionotronic sensing system. Consequently, this work provides a guideline for the design of ionotronic materials for the achievement of high-performance and skin-attachable gas-sensor platforms.

14.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1866(5): 158904, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33578049

RESUMO

OBJECTIVE: The purpose of this study was to explore the role of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in atherosclerosis and the underlying mechanism. METHODS: The Gene Expression Omnibus (GEO) datasets were used to divide differentially expressed lncRNAs, microRNAs (miRNAs), and mRNAs. The expression of PCA3, miR-140-5p, RFX7 and ABCA1 were determined by qPCR or Western blot in ox-LDL-treated macrophages. Macrophage lipid accumulation s was evaluated using the Oil Red O staining and high-performance liquid chromatography. Target relationships among PCA3, miR-140-5p, RFX7, and ABCA1 promoter area were validated via dual-luciferase reporter gene assay or chromatin immunoprecipitation assay. The apoE-/- mouse model in vivo was designed to evaluate the effect of PCA3 on the reverse cholesterol transport (RCT) and atherosclerosis. RESULTS: PCA3 was down-regulated in foam cells, whereas miR-140-5p was highly expressed. Overexpression of PCA3 promoted ABCA1-mediated cholesterol efflux and reduced lipid accumulation in macrophages. Besides, RFX7 bound to the ABCA1 promoter and increased ABCA1 expression. Targeted relationships and interactions on the expression between miR-140-5p and PCA3 or RFX7 were elucidated. PCA3 up-regulated ABCA1 expression by binding to miR-140-5p to up-regulate RFX7 and ABCA1 expression in macrophages. PCA3 promoted RCT and impeded the progression of atherosclerosis by sponging miR-140-5p in apoE-/- mice. Meanwhile, miR-140-5p also inhibit ABCA1 expression via downregulation of RFX7 to impede RCT and aggravate atherosclerosis. CONCLUSIONS: lncRNA PCA3 promotes ABCA1-mediated cholesterol efflux to inhibit atherosclerosis through sponging miR-140-5p and up-regulating RFX7.

15.
Cancer Med ; 10(6): 1925-1935, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33641255

RESUMO

BACKGROUND: Current the surveillance and management are controversial for patients with IPMN. We aimed to develop an alternative nomogram to individualize IPMN prognosis and LNM. METHODS: Based on the data from SEER database of patients diagnosed with IPMN between 2004 and 2015, a nomogram predicting the survival and LNM of IPMN based on univariate and multivariate and Lasso regression analysis was performed, internally and externally validated, and measured by C-index, and decision curve analysis (DCA), and compared to the 7th TNM stage. RESULTS: A total of 941 patients were included. Age, T stage examined nodes, tumor size, and pathology grade were identified as an independent factor for predicting LNM. The nomogram we established to predict LNM had a high predicting value with a C-index value of 0.735 and an AUC value of 0.753. Interestingly, including T1 stage, we found an inverse correlation was between age and LNM. In addition, nomogram for predicting CSS also performed better than TNM stage both in the internal validation group (1-year AUC:0.753 vs. 0.693, 3-year AUC: 0.801 vs. 0.731, 5-year AUC: 0.803 vs. 0.733) and external validation group (1-year AUC: 0.761 vs. 0.701, 3-year AUC: 0.772 vs. 0.713, 5-year AUC:0.811 vs. 0.735). DCA analysis showed the nomogram showed a greater benefit across the period of follow-up compared to 7th TNM stage. CONCLUSION: A nomogram based on multivariate and Lasso regression analysis showed great clinical usability compared with current criteria. Also, for LNM of IPMN, younger age patients with IPMN should be attached more importance.

16.
Cell Host Microbe ; 29(3): 489-502.e8, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33548198

RESUMO

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-ß levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-ß responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.


Assuntos
/imunologia , Interferon Tipo I/imunologia , /imunologia , Proteínas não Estruturais Virais/genética , Células A549 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Sequência de Bases , Linhagem Celular , Criança , Pré-Escolar , Chlorocebus aethiops , Feminino , Deleção de Genes , Genômica , Células HEK293 , Humanos , Lactente , Interferon Tipo I/sangue , Interferon beta/sangue , Interferon beta/metabolismo , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Genética Reversa , Células Vero , Proteínas não Estruturais Virais/imunologia , Adulto Jovem
17.
Aging (Albany NY) ; 13(4): 5164-5184, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535178

RESUMO

The Notch1-mediated inflammatory response participates in the development of abdominal aortic aneurysm (AAA). The vascular endogenous bioactive peptide intermedin (IMD) plays an important role in maintaining vascular homeostasis. However, whether IMD inhibits AAA by inhibiting Notch1-mediated inflammation is unclear. In this study, we found Notch intracellular domain (NICD) and hes1 expression were higher in AAA patients' aortas than in healthy controls. In angiotensin II (AngII)-induced AAA mouse model, IMD treatment significantly reduced AAA incidence and maximal aortic diameter. IMD inhibited AngII-enlarged aortas and -degraded elastic lamina, reduced NICD, hes1 and inflammatory factors expression, decreased infiltration of CD68 positive macrophages and the NOD-like receptor family pyrin domain containing 3 protein level. IMD inhibited lipopolysaccharide-induced macrophage migration in vitro and regulated macrophage polarization. Moreover, IMD overexpression significantly reduced CaCl2-induced AAA incidence and down-regulated NICD and hes1 expression. However, IMD deficiency showed opposite results. Mechanically, IMD treatment significantly decreased cleavage enzyme-a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) level. Pre-incubation with IMD17-47 (IMD receptors blocking peptide) and the phosphatidylinositol 3-kinase/protein kinase b (PI3K/Akt) inhibitor LY294002 reversed ADAM10 level. In conclusion, exogenous and endogenous IMD could inhibit the development of AAA by inhibiting Notch1 signaling-mediated inflammation via reducing ADAM10 through IMD receptor and PI3K/Akt pathway.

18.
Nanoscale ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522533

RESUMO

Two-dimensional (2D) carbon allotropes with topologically nontrivial states are drawing considerable attention owing to their unique physical properties and great potential applications in the next generation of micro-nano devices. In contrast to the numerous Dirac points predicted in 2D carbon allotropes, systems featuring Dirac nodal lines (loops) are still quite rare. Here, by means of first-principles calculation, we report our newly discovered carbon monolayer 123-E8Y24-1 with robust Dirac nodal line states, which possesses a tetragonal lattice with P4/mmm symmetry and contains 8 sp2 carbon atoms (graphene: E8) and 24 sp carbon atoms (grapheyne: Y24) in the crystalline cell. This 2D material is as energetically stable as the recently experimentally synthesized ß-graphdiyne, and it is further predicted to be dynamically, mechanically, and also thermodynamically stable. Owing to its intrinsic geometric characteristics, 123-E8Y24-1 also exhibits obvious Young's modulus anisotropy, with a sizable ratio between the maximum and minimum value of up to 5.8. Remarkably, 123-E8Y24-1 presents a semimetal nature and possesses Dirac nodal line states in the electronic band structure, and such behavior could be kept well under external strain between -10.0% and 8.0%. The electronic properties of 123-E8Y24-1 can be carefully confirmed by constructing a tight-binding (TB) model. The findings presented in this paper reveal a novel 2D Dirac nodal loop carbon sheet, providing a new candidate for carbon-based high-speed electronic devices.

19.
Environ Res ; 195: 110738, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33485910

RESUMO

BACKGROUND: As the global climate continues to warm, there is an increased focus on heat, but the role of low temperatures on health has been overlooked, especially for developing countries. Methods We collected the admission data of childhood asthma in 2013-2016 from Anhui Provincial Children's Hospital, as well as meteorological data from the Meteorological Bureau for the study period and collected data of pollutants from 10 monitoring stations around Hefei city. Poisson's generalized additive model (GAM) combined with a distributed lag non-linear model (DLNM) was used to estimate the short-term effects of cold spell on childhood asthma in cold seasons (November to March). 16 definitions of cold spells were clearly compared, which combining 4 temperature indexes (daily minimum and mean temperature; daily minimum and mean apparent temperature), 2 temperature thresholds (2.5th and 5th) and 3 durations of at least 2-4 days. We then have an analysis of the modifying effect of characteristics of cold spells and individuals(gender and age), with a view to discovering the susceptible population to cold spell. Results There was significant association between cold spells and admission risk for childhood asthma. And the definition, in which daily minimum apparent temperature falls below 5th percentile for at least 3 consecutive days, produced the optimum model fit performance. Based on this optimal fit we found that, for the total population, the effect of cold spell lasted approximately five days (lag1-lag5), with the largest effect occurring in lag 3 (RR = 1.110; 95% CI: 1.052-1.170). In subgroup analysis, the cumulative effect of lag0-7 was higher in males and school-age children than in females and other age groups, respectively. In addition, we found that the effect of is higher as the duration increases. Conclusion This study suggests an association between cold spell and childhood asthma, and minimum AT may be a better indicator to define the cold spells. Boys and school-age children are more vulnerable to cold spell. And one of our very interesting findings is that if a cold spell lasts for several days, the impact of the cold spell on those later days is likely to be greater than that of the previous days. In conclusion, we should pay more attention to the protection of boys and school-aged children in our future public health protection and give more attention to those cold spells that last longer. Therefore, we recommend that schools and health authorities need to take targeted measures to reduce the risk of asthma in children during the cold spell.


Assuntos
Asma , Temperatura Baixa , Asma/epidemiologia , Criança , China , Cidades , Feminino , Hospitalização , Humanos , Masculino , Temperatura
20.
Cell Death Dis ; 12(1): 129, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504767

RESUMO

CAR-T transfer, recently well-developed immunotherapy, has offered substantial benefit to more and more patients with advanced cancers. However, along with growing experience in the clinical application comes the increasing awareness of the potentially fatal adverse effects, most notably cytokine release syndrome (CRS) and neurotoxicity. Understanding the mechanisms underlying these toxicities can help to improve therapeutic outcomes. Recent findings highlight the importance of monocyte/macrophage in CAR-T-related toxicities (CARTOX) and shed light on a novel mechanism mediated by damage-associated molecular patterns (DAMPs) released from pyroptotic cells. Therefore, this review summarizes these findings and provides practical guidance to the management of CARTOX.

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